Australia & New Zealand Breast Cancer Trials Group

Transcription

1 Annual Report 2014/2015

2 Australia & New Zealand Breast Cancer Trials Group Web: or scan the following QR code: Trials Coordination Department Australia & New Zealand Breast Cancer Trials Group PO Box 155 Hunter Region Mail Centre NSW 2310 Australia Ph: (+61) Fax: (+61) Business Department Australia & New Zealand Breast Cancer Trials Group PO Box 283 The Junction NSW 2291 Australia Ph: (+61) Fax: (+61) Fundraising & Education Department Breast Cancer Institute of Australia PO Box 283 The Junction NSW 2291 Australia Ph: (+61) Fax: (+61) enquiries@bcia.org.au Web: ANZ Breast Cancer Trials Group Limited ACN ABN ATO N This report cannot be reproduced without the permission of the ANZ Breast Cancer Trials Group Ltd. All rights reserved.

3 Australia and New Zealand Breast Cancer Trials Group Our mission To eradicate all suffering from breast cancer through the highest quality clinical trials research. Our vision To be a global and regional leader in research collaboration committed to a world without breast cancer. Our values Excellent, Relevant, Transparent, Reputable, Inclusive, Innovative. Contents About Us 2 Chair s Report 4 Chief Operating Officer s Report 6 Research Report 8 Clinical Trials Open for Participant Entry 18 Clinical Trials Accrual Completed 34 Communication Report 36 Consumer Advisory Panel Report 38 Fundraising Report 40 Fundraising Results and Highlights 42 Governance 56 Contributors and Supporters 62 Financial Report 66 Publications 70 Glossary of Terms 74 ANZBCTG Annual Report

4 About Us The Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) is the largest independent, oncology clinical trials research group in Australia and New Zealand. For more than 35 years, the ANZBCTG has conducted a national clinical trials research program for the treatment, prevention and cure of breast cancer. The research program rigorously and scientifically tests the efficacy of new breast cancer treatments and prevention interventions through the conduct of multicentre national and international clinical trials. The Breast Cancer Institute of Australia (BCIA) is the fundraising and education department of the ANZBCTG and was established in 1994 to increase awareness of, and seek ongoing funding for, the ANZBCTG research program. Our aim is to eradicate all suffering from breast cancer and achieve the ultimate goal of a world without breast cancer There are more than 700 members of the ANZBCTG, including surgeons, oncologists, study coordinators, nurses and breast physicians for example, who are involved in the conduct of the ANZBCTG s research program. The ANZBCTG s research program encompasses 75 clinical trials including: ongoing clinical trials that are open for patient recruitment; trials that have closed to recruitment but are in an active follow-up phase; and completed clinical trials that have been analysed and published. 14,000 More than 14,000 women from Australia and New Zealand have participated in our breast cancer clinical trials research program. $67m The Breast Cancer Institute of Australia has raised more than $67 million since 1995, so that ANZBCTG researchers can pursue the very best science. 940 The ANZBCTG has contributed to more than 940 publications. 87 The ANZBCTG research program brings together 87 institutions throughout Australia and New Zealand. 2 ANZBCTG Annual Report

5 Participating Institutions NT WA QLD SA NSW AUSTRALIA VIC ACT NEW ZEALAND TAS Armidale Hospital Auckland City Hospital Austin Hospital Ballarat Health Services Ballarat Oncology and Haematology Services Bankstown-Lidcombe Hospital Border Medical Oncology Box Hill Hospital Cabrini Hospital Cairns Hospital Calvary Mater Newcastle Christchurch Hospital Coffs Harbour Health Campus Concord Repatriation General Hospital Dunedin Hospital Epworth Richmond Hospital Fiona Stanley Hospital Flinders Medical Centre Footscray Hospital Frankston Hospital Frankston Private Gosford Hospital Goulburn Valley Health Icon Cancer Care Wesley Launceston General Hospital Lismore Base Hospital Liverpool Hospital Lyell McEwin Hospital Macarthur Cancer Therapy Centre Macquarie Cancer Clinical Trials Manning Rural Referral Hospital Maroondah Hospital Mater Adult Hospital Mater Cancer Care Centre Mater Hospital Sydney Mersey Community Hospital Monash Breast Clinic Monash Cancer Centre Monash Medical Centre Mount Hospital Nambour Hospital Nepean Cancer Care Centre Newcastle Private Hospital North Shore Hospital North West Regional Hospital Orange Health Service Palmerston North Hospital Peter MacCallum Cancer Centre Port Macquarie Base Hospital Prince of Wales Hospital Princess Alexandra Hospital Riverina Cancer Care Centre Royal Adelaide Hospital Royal Brisbane and Women s Hospital Royal Hobart Hospital Royal North Shore Hospital Royal Perth Hospital Royal Prince Alfred Hospital Sans Clinical Trials Unit Sir Charles Gairdner Hospital Southern Highlands Cancer Centre St Andrew s Toowoomba Hospital St George Hospital Sydney St George s Hospital Christchurch St John of God Hospital Bunbury St John of God Hospital Subiaco St Vincent s Hospital Melbourne St Vincent s Hospital Sydney Sunshine Hospital Tamworth Rural Referral Hospital The Alfred Hospital The Bendigo Hospital The Breast & Endocrine Centre The Canberra Hospital The Chris O Brien Lifehouse The Northern Hospital The Queen Elizabeth Hospital The Royal Melbourne Hospital The Royal Women s Hospital The Tweed Hospital Townsville Hospital University Hospital Geelong Victorian Breast & Oncology Care Waikato Hospital Wellington Hospital Westmead Hospital Wollongong Hospital ANZBCTG Annual Report

6 Chair s Report Professor Frances Boyle AM The significance of breast cancer clinical trials is best explained when you put a face to the research, to help demonstrate how new treatment discoveries are saving and changing women s lives. We saw some fantastic results from the research program of the Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) this year, including the POEMS clinical trial. The results of this international study offers a new treatment option for young women with breast cancer, to better preserve their fertility during cancer treatment. One of my own patients, Natasha, participated in this study and the impact this new treatment had on Natasha s life was fantastic. Natasha was diagnosed with breast cancer at 32 and was told she might not be able to have children, due to the side effects of receiving chemotherapy treatment. The POEMS clinical trial examined whether treatment with the drug goserelin allowed women s ovaries to recover after chemotherapy, while not interfering with the cancer treatment itself. The study found that women who received goserelin were less likely to be in menopause two years after their cancer treatment (8% compared with 22%) and were twice as likely to have a normal pregnancy after their cancer treatment. After participating in the POEMS clinical trial, Natasha fell pregnant with her son Jack the Christmas following her treatment. A wonderful outcome for this family. As the Chair of the ANZBCTG, and throughout my own career, I have seen first-hand how clinical trials research is making a difference in our community. The collaboration between women who participate in our research program, our members and participating institutions around Australia and New Zealand, and the support we receive from individual donors and corporate supporters, help make these new breakthroughs in research a reality. During the reporting period, the ANZBCTG had a number of significant achievements: Approval of the Strategic Plan, which provides direction and guidance for the activities of the Group and highlights our priorities; The results of the TEXT, SOFT, ALTTO and POEMS clinical trials were published; Avon, through the hard work and generosity of their Representatives and customers, made a remarkable donation of $1 million to our research program. This is their largest, single donation in our 18 year partnership and brings the total donated to $9.4 million. We re indebted to Avon for their generosity and long term commitment to identifying more treatment options for all those affected by breast cancer through clinical trials research; 10 clinical trials were open to recruitment during the reporting period and we continued to collect participant follow-up data for 19 international trials; 4 ANZBCTG Annual Report

7 The Group reported net income of $2.173 million, with increased income from the clinical trials program (due to increased activity) and increases in both fundraising and investment income, which places us in a strong position to fund our research program; The ANZBCTG contributed to 33 peer reviewed publications; The 2015 Australian Women s Health Diary set a new record, making a $1.1 million profit this year; A successful Annual Scientific Meeting in Wellington, New Zealand. Breast Cancer Institute of Australia The Breast Cancer Institute of Australia celebrated its 20-year anniversary during the reporting period and on behalf of the Board of Directors and our members, I sincerely thank BCIA General Manager Julie Callaghan and her staff. The BCIA has raised a total of $67 million towards the ANZBCTG s breast cancer clinical trials research program, which has helped find new and improved treatment and prevention options for women at risk of, or diagnosed with, breast cancer. Quite simply, without the support of donors and our corporate supporters, such as Avon, The Commonwealth Bank and The Australian Women s Weekly, our research program would not be possible. Thank you also to Dr Colin Furnival who helped establish and progress our fundraising in his capacity as our Responsible Person for Queensland activities from Colin s assistance and support of the BCIA has been invaluable. Governance The ANZBCTG Board of Directors is comprised of six elected Directors and four appointed Directors, who bring a range of medical, research and/or business expertise to the table. Professor John Simes and Associate Professor Ian Campbell both completed their terms as Directors during the reporting period. Professor Simes is Director of the ANZBCTG Statistical Centre located at the NHMRC Clinical Trials Centre and was elected to the Board in Associate Professor Campbell is a Surgeon at Waikato Hospital in New Zealand and was elected to the Board in We thank both John and Ian for their many years of contribution to the Board of Directors. During the reporting period, we welcomed Dr Richard Isaacs to the Board. Dr Isaacs is a Medical Oncologist at Palmerston North Hospital in New Zealand. We also welcomed Mr Paul Field, a Senior Investment Specialist at the Australian Trade Commission. Summary This is a very exciting time for clinical trials research. In the era of treatments based on understanding cell biology, more research is focusing on how we can tailor treatments for women that are specific to their type of breast cancer. This will hopefully mean optimal protection from breast cancer with a minimum of side effects. Our global connections will be required to ensure Australian women benefit as rapidly as possible from these new developments. I thank you all for your continued enthusiasm and support. Professor Fran Boyle AM Chair, Board of Directors ANZBCTG Annual Report

8 Chief Operating Officer s Report Dr Soozy J Smith This year marked the start of our revised Strategic Plan and it was particularly pleasing to engage with our many stakeholders to develop it. The ANZBCTG continues to focus on innovative clinical trials and we have had a particularly busy year activating no less than six trials. All staff have worked extremely hard to ensure that we meet deadlines, manage the ever increasing governance requirements placed on the Group and to provide support to our members wherever we can. Our Board give freely of their time and their support and advice is greatly appreciated. I count myself very fortunate that I can come to work every day for a worthy cause supported by a wonderful group of people who are working towards the common goal. Strategic Plan During the reporting period, the ANZBCTG Board of Directors approved the Strategic Plan which outlines our key priorities for this period. Four main success pillars will guide our research, fundraising and operational activities: High quality clinical trials; Collaboration and partnerships; Organisational best practices; Respected information resource on breast cancer clinical trials. Underpinning these pillars and the strategies involved to achieve these goals are Finance, Fundraising, Communication and Risk Assessment Plans for the same period. Operations There are approximately 50 staff at the ANZBCTG across our three departments of Business, Research and Fundraising and Education, and it is a pleasure to work with staff who are committed to our vision of a world without breast cancer. Each staff member brings with them a unique set of skills and together we are making a difference for women with breast cancer. The ANZBCTG acknowledges and recognises staff for their length of service and thanks them for their invaluable contribution and continued support. This year we recognised the following staff members: 15 years (plus) - Akiko Fong and Jenny Leggett; 10 years (plus) - Annette Dempsey, Nicole Francis, Leigh Hainsworth and Christine Wasik; 5 years (plus) - Anna Cummins and Mai Ly. 6 ANZBCTG Annual Report

9 Financial Position The nature of breast cancer clinical trials means that it can take many years for important scientific research to be published and it is essential that the ANZBCTG be in a position to be able to fund this important research and clinical trials into the future. I am pleased to report that a solid financial strategy, led by our Financial Controller Mr David Pringle and supported by our Finance and Audit Committee, has laid a strong foundation for our research program to continue to expand and follow up existing trials. I would also like to acknowledge: our funding bodies, which includes the Breast Cancer Research Foundation (USA), Cancer Australia, the National Health and Medical Research Council and The University of Newcastle; as well as the continued support of our corporate supporters and donors; who all contribute to the research, education and capacity building initiatives within the Group. For details on the Group s financial position please refer to page 66. Summary For more than 35 years, the ANZBCTG has conducted the highest quality breast cancer clinical trials research in Australia and New Zealand, which has made a significant contribution to improved treatments available to women today. Not only do we have a strong history of international collaboration but we have also supported our local researchers and their important research ideas. Our strong financial position, together with the breadth of talent among our members and staff, will help to ensure that our reputation as a global and regional leader in clinical trials research will continue into the future. Dr Soozy J Smith Chief Operating Officer ANZBCTG Annual Report

10 Research Report Professor John Forbes AM Associate Professor Nicholas Wilcken Associate Professor Prue Francis Dr Nicholas Zdenkowski Mrs Dianne Lindsay The Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) is the largest independent, oncology clinical trials research group in Australia and New Zealand. The year in review has seen solid achievements and continued progress in the design, conduct, analysis and publication of our clinical trials. The support of our patients who volunteer to take part in clinical trials and the contribution of our clinical researchers has led to a number of high quality publications. A number of major international clinical trials were analysed and published during the reporting period and the results are summarised below: Analysis and publication of the first results of the IBCSG 24-02/BIG 2-02 SOFT and IBCSG 25-02/BIG 3-02 TEXT clinical trials which compared adjuvant therapy with exemestane or tamoxifen plus ovarian function suppression. The results are summarised below; Analysis and publication of the IBCSG 24-02/BIG 2-02 SOFT clinical trial, which investigated the value of adjuvant ovarian suppression in premenopausal breast cancer patients. The results are summarised on page 9; Analysis and publication of the IBIS-I breast cancer prevention trial showed that treatment benefit extends post 10 years. The results are summarised on page 10; Publication of research aiming to develop a new online tool to assess and manage breast cancer risk in primary care in Australia. The results are summarised on page 10; Analysis and publication of the first results of TRIO-012/ROSE, which evaluated the addition of ramucirumab to docetaxel chemotherapy in metastatic breast cancer. The results are summarised on page 11; Analysis and publication of the first results of the POEMS clinical trial, contributing to evidence that the administration of a GnRH analogue protects against chemotherapy-induced premature ovarian failure. The results are summarised on page 11. Publications A number of new publications which answer clinically important questions are expected to translate into improved outcomes for women, particularly a suite of complementary clinical trials designed for premenopausal patients with hormone-sensitive breast cancer. The results underline the contribution of many of our members who share a dedication to providing the evidence base to guide clinical practice and assist patients and their doctors to choose appropriate, effective treatments for breast cancer. A full list of these publications is available on page 70. Six of the papers are summarised below: Combined results of landmark studies IBCSG 24-02/BIG 2-02 SOFT and IBCSG 25-02/BIG 3-02 TEXT Around four in every five premenopausal women diagnosed with breast cancer in Australia have hormone-sensitive breast cancer. There is an identified link between oestrogen and the stimulation of cancer cell growth; this may contribute to the poorer prognosis experienced by younger, premenopausal women 8 ANZBCTG Annual Report

11 who retain premenopausal levels of oestrogen following a diagnosis of breast cancer. Triptorelin, a medication that suppresses ovarian function (GnRH agonist), can minimise the impact of naturally occurring oestrogen on breast cancers by suppressing its production. Alternative methods of suppressing ovarian function include surgical removal or radiotherapy. Currently, premenopausal women with hormone-sensitive breast cancer receive treatment with tamoxifen and postmenopausal women receive treatment with either aromatase inhibitors (AI) or tamoxifen as standard of care. Earlier clinical trials demonstrated the superiority of AIs over tamoxifen in the treatment of hormone-sensitive breast cancer in postmenopausal women. The SOFT and TEXT clinical trials investigated whether the benefit of AIs over tamoxifen could be translated to women who were premenopausal by using triptorelin, surgery or radiotherapy to induce a postmenopausal state. SOFT and TEXT both randomly assigned premenopausal women with hormone-sensitive breast cancer to receive post-operative treatment with either an AI, exemestane, plus ovarian suppression for five years, or tamoxifen plus ovarian function suppression for five years. Approximately half of the patients also received chemotherapy. The two clinical trials were designed to be complementary and the use of a combined analysis allowed the results to be available earlier than if they had been analysed separately. This analysis combined data from 4,690 patients in the two clinical trials; in total the ANZBCTG recruited 240 women to SOFT (n=3,066) and 249 women to TEXT (n=2,672). The combined results of SOFT and TEXT at a median follow-up of 68 months indicated that exemestane plus ovarian function suppression was superior to tamoxifen plus ovarian function suppression. The combination of exemestane plus ovarian function suppression reduced the risk of developing any invasive cancer by 28% and reduced the risk of developing further breast cancers by 34% compared to treatment with tamoxifen plus ovarian function suppression. The research found that at five years these women s overall prognosis was good: 92.8% assigned to receive exemestane plus ovarian function suppression remained free from breast cancer compared to 88.8% assigned to tamoxifen plus ovarian function suppression. Overall quality of life was similar in both groups, while specific side effects were similar to those seen in postmenopausal women receiving treatment with an AI or tamoxifen. These significant results show that five years of ovarian suppression plus exemestane is a new treatment option to reduce the chance of breast cancer recurrence and improve outcomes for young women diagnosed with hormone-sensitive early stage breast cancer. This paper was published in the New England Journal of Medicine 2014; 371(2): , please refer to page 71. IBCSG 24-02/BIG 2-02 SOFT: New results benefit young women with breast cancer Premenopausal women diagnosed with hormone-sensitive breast cancer at a very young age (less than 35 years) have a higher chance of their breast cancer returning despite receiving chemotherapy. Researchers believe this is due to the continued production of oestrogen in the ovaries which encourages cancer cell growth, even after chemotherapy. If ovarian function is suppressed, hormone-sensitive breast cancers are less likely to grow. Treatment with chemotherapy, hormone treatments such as tamoxifen and ovarian function suppression with the drug triptorelin, surgery or radiation therapy all reduce the risk of breast cancer returning in young women with hormone-sensitive breast cancer. Tamoxifen (hormone treatment) is the current standard of care for premenopausal women diagnosed with hormone-sensitive breast cancer. The Suppression of Ovarian Function Trial (SOFT) investigated three different hormonal treatment options: tamoxifen, tamoxifen plus ovarian function suppression, and exemestane plus ovarian function suppression. The primary intent of this trial was to determine if tamoxifen plus ovarian function suppression is superior to tamoxifen alone in women who were premenopausal after surgery and chemotherapy (if received) for early stage breast cancer. International recruitment to SOFT included 3,066 women of whom 240 were recruited from Australia and New Zealand. Overall, after a median follow-up of 67 months, there was no significant difference in the chance of breast cancer recurrence between the women who were given tamoxifen and those given tamoxifen plus ovarian ANZBCTG Annual Report

12 function suppression. However, analysis of groups of women within the trial demonstrated that it may be possible to select patients most likely to benefit from additional hormonal treatment. The addition of ovarian function suppression to tamoxifen reduced the recurrence of hormone-sensitive breast cancer in women who were premenopausal despite having received chemotherapy (average age 40 years). Women younger than 35 years, an age group at higher risk of recurrence, received greater benefit: 17% of these women who received exemestane plus ovarian function suppression experienced a breast cancer recurrence, compared to 21% who received tamoxifen plus ovarian function suppression and 32% in the group who received tamoxifen alone. SOFT also investigated whether ovarian function suppression benefited women who, in consultation with their doctor, did not receive chemotherapy for their breast cancer. These women were older (average age 46 years), closer to natural menopause onset and had a breast cancer with a more favourable prognosis on pathology, compared to women who received chemotherapy. More than 95% of women in this group were free from breast cancer recurrence after five years with tamoxifen alone and for these women there was no significant difference in outcomes between the different treatments. This clinical trial showed that adding ovarian function suppression to tamoxifen did not improve outcomes significantly for the overall trial population. However, women at higher risk of recurrence who receive chemotherapy and remain premenopausal may benefit from the addition of ovarian function suppression, and benefit even more from the combination of ovarian function suppression plus exemestane. The results are potentially practice changing and are a positive step forward in treating young women with hormone-sensitive breast cancer. This paper was published in the New England Journal of Medicine. 2015; 372(5): , please refer to page 71. Extended long-term follow-up of the IBIS-I breast cancer prevention trial Between 1992 and 2001 the IBIS-I clinical trial recruited 7,154 women, including 2,674 from Australia and New Zealand. Pre- and postmenopausal women at high risk of developing breast cancer were randomised to receive either tamoxifen or placebo for five years. Risk was estimated based on family history or a personal history of lobular carcinoma in situ or atypical hyperplasia. The present manuscript describes results after a median follow-up of 16 years, at which time 601 cases of either breast cancer or ductal carcinoma in situ were reported across both arms, 251 (7%) in the tamoxifen arm (n=3,579) and 350 (9.8%) in the placebo arm (n=3,575). At the time of this analysis, treatment allocation remained largely masked to both investigators and participating women. The benefit in terms of breast cancer risk reduction that was seen in the years 0-10 analysis was maintained beyond 10 years. The greatest reduction in risk was seen in invasive hormone-sensitive (oestrogen-receptor-positive) breast cancers and ductal carcinomas in situ. No effect was noted for invasive breast cancer that was not hormone-sensitive (oestrogen-receptor-negative). These trial results indicate that the benefit of tamoxifen treatment extends for at least 10 years beyond treatment cessation and that breast cancer can be effectively prevented in women who are at high risk of developing hormone-sensitive breast cancer. These results were published online in the Lancet Oncology 2015; 16:67-75, please refer to page 70. Strategies to manage breast cancer risk: a new tool in development Despite advances in our ability to determine an individual woman s risk for breast cancer, most Australian women are not aware of their personal risk for developing the disease. Approximately 85% of Australians visit a primary care physician at least once per year, providing a chance for a formal breast cancer risk assessment in the primary care setting. However, breast cancer risk assessment is not routinely undertaken in this setting, and is often only initiated at the patient s request. This may be a missed opportunity for a risk-adapted approach to breast cancer prevention and screening. This research examined the needs of primary care clinicians regarding the assessment and management of breast cancer risk. 10 ANZBCTG Annual Report

13 Two focus groups with general practitioners and primary care nurses were convened. Participants endorsed an online tool, such as those currently used in the assessment of cardiovascular risk, to assist primary care clinicians to better assess an individual s breast cancer risk. The paper identified a number of barriers to the acceptability of assessing breast cancer risk, however concluded that there is an opportunity to use a breast cancer risk assessment and risk management tool, particularly if it is easily accessible and was endorsed by experts. These results have informed the development of an online breast cancer risk assessment and risk management tool which is now undergoing preliminary testing with women. The research described in this publication was supported by the ANZBCTG from public donations made to the Breast Cancer Institute of Australia, and helped secure a grant from the National Health and Medical Research Council to complete development of the online tool and to continue preliminary testing. It is hoped that the tool will transform the way breast cancer risk is assessed and managed in Australia. This paper was published online in the Australian Journal of Primary Health. 2015; epub 24 Feb 2015, please refer to page 72. TRIO-012 / ROSE: evaluating the addition of ramucirumab to docetaxel chemotherapy Antiangiogenic agents are a type of anti-cancer drug that limit the growth of new blood vessels, which may assist in the treatment of breast cancer by restricting the growth of the tumour s blood supply or by increasing the tumour s sensitivity to chemotherapy agents. The use of these agents to treat cancer have demonstrated modest improvements in progression-free survival (PFS) but have not improved patient s quality of life or duration of survival. Ramucirumab is a new type of antiangiogenic agent comprised of a human immunoglobulin G1 antibody which blocks ligand-stimulated activation of blood vessel growth factors. The Ramucirumab Overall Survival Evaluation (ROSE) / TRIO-012 clinical trial recruited women with HER2-negative, metastatic breast cancer who had not received chemotherapy or biologic therapy for advanced breast cancer. Between 2008 and 2011, 1,144 participants (60 from Australia and New Zealand) were recruited to this trial from 234 institutions located throughout 22 countries. Women were randomised 2:1 to receive docetaxel plus ramucirumab or docetaxel plus placebo every three weeks until disease progression, unacceptable toxicity or other withdrawal criteria were met. The primary trial end point was investigator assessed progression-free survival. The primary analysis demonstrated a median progression-free survival for participants treated with ramucirumab of 9.5 months compared to 8.2 months for participants who received placebo. Overall survival was equivalent at 27 months in both arms. Women treated with the combination therapy also experienced more side effects. While this trial found that the combination of ramucirumab and docetaxel was no better than docetaxel alone, the research has contributed to the understanding of the role of antiangiogenic agents in the treatment of HER2-negative breast cancer. Further work is underway to better understand how breast cancer responds to antiangiogenic therapies, focusing on molecularly defined targets and other relevant biomarkers to identify which patients might benefit from this treatment. This paper was published in the Journal of Clinical Oncology 2015; 33(2): , please refer to page 71. IBCSG / SWOG S0230 POEMS: New option for preserving fertility in women receiving chemotherapy for early stage breast cancer Early menopause is a common long term side effect for young women receiving chemotherapy treatment for breast cancer, preventing fertility and increasing the risk of long term medical problems including osteoporosis and heart disease. The use of gonadotropin-releasing hormone (GnRH) agonists to protect the ovaries during chemotherapy has been studied previously, however results have been conflicting and had limited data on pregnancy outcomes. ANZBCTG Annual Report

14 The Prevention Of Early Menopause Study (POEMS) recruited 257 premenopausal women between the ages of 18 to 49 with breast cancer that was not hormone-sensitive (oestrogen- and progesterone-receptornegative). Interest in future pregnancy was not required for eligibility. Participants were randomised 1:1 to receive standard chemotherapy with concurrent goserelin (a GnRH agonist) or chemotherapy alone. The primary endpoint for POEMS was ovarian failure at two years, defined by the absence of menses in the preceding six months and follicle-stimulating hormone (FSH) levels in the postmenopausal range. At baseline, 218 women with a median age of 37.7 years were eligible for evaluation. Approximately 20% (n=58) of participants in POEMS were recruited from Australia and New Zealand. Among 135 women with data on menstrual cycle and FSH at two years after study enrolment, the ovarian failure rate was 8% in the goserelin plus chemotherapy group compared to 22% in the chemotherapy alone group. More pregnancies occurred in the goserelin plus chemotherapy group than the standard therapy group (21% vs 11%). Furthermore, women who received goserelin during their chemotherapy had an improved disease-free survival and overall survival. Pregnancies were reported in 11% of women who received chemotherapy alone, with 7% delivering a total of 12 babies; two women were pregnant at the time of data submission. Pregnancies were reported in 21% of the women who received goserelin with chemotherapy, with 15% delivering a total of 18 babies; three other women were pregnant at the time of data submission. The results of this clinical trial have generated great interest in goserelin for premenopausal women with hormone-receptor-negative breast cancer during chemotherapy, in order to mitigate the long term effects of chemotherapy induced early menopause and provide a viable option for preserving fertility. This paper was published in the New England Journal of Medicine 2015; 372: , please refer to page 71. Annual Scientific Meeting We were pleased to welcome an outstanding faculty to our Annual Scientific Meeting (ASM) in July 2014 in Wellington, New Zealand. More than 180 ANZBCTG members and international guest speakers participated in an exceptional scientific program, which brought together experts to present the latest research and developments in breast cancer control. The ASM helps to establish links with other international breast cancer trials groups and has led to valuable new collaborations. International speakers at the 2014 ASM Dr Cliff Hudis, Memorial Sloan-Kettering Cancer Center, USA; Professor Robert Mansel, Cardiff University, UK; Dr W. Fraser Symmans, MD Anderson Cancer Center, USA. ANZBCTG Awards The ANZBCTG Gold Medal The ANZBCTG Gold Medal recognises the outstanding contribution and achievements of a member of the ANZBCTG, who has played a significant role in the development and conduct of breast cancer clinical trials research in this region. The Medal is awarded at the discretion of the ANZBCTG Board of Directors. The 2014 recipient was Associate Professor Raymond Snyder from St Vincent s Hospital in Melbourne. Associate Professor Snyder was one of the founding members of the ANZBCTG and a past Chair of the Board of Directors from Chair of the ANZBCTG Board of Directors Professor Fran Boyle presents the ANZBCTG Gold Medal to Associate Professor Raymond Snyder. 12 ANZBCTG Annual Report

15 The Robert Sutherland Award for Excellence in Translational Research The Robert Sutherland Award for Excellence in Translational Research recognises Translational Researchers and their achievements and contributions to improved patient outcomes. The award is open to Translational Researchers worldwide. The recipient receives a travel grant to attend and present a lecture at the ANZBCTG ASM and up to $10,000 for professional development or research activities. The 2014 recipient was Dr W. Fraser Symmans from the MD Anderson Cancer Center in Texas, USA. Dr W. Fraser Symmans receives The Robert Sutherland Award from ANZBCTG Board Chair Professor Fran Boyle. The Alan Coates Award for Excellence in Clinical Trials Research The Alan Coates Award for Excellence in Clinical Trials Research recognises a member of the ANZBCTG who has made an outstanding contribution to the ANZBCTG s clinical trials research program. It aims to assist the recipient in their professional development with a travel grant to attend the ANZBCTG ASM and up to $10,000 for professional development activities. The 2014 recipient was Professor Michael Green from the Royal Melbourne Hospital in Victoria. Professor Michael Green receives The Alan Coates Award from Professor Alan Coates and Professor Fran Boyle. The John Collins Fellow Medal and Travel Grant This award was established to encourage potential academic breast cancer Surgeons and Registrars to become involved in clinical trials research. The award recipient receives a grant to travel to the ANZBCTG ASM to learn about current breast cancer clinical trials and participate in discussions and plans for future Australian and international studies, and network with experienced breast cancer clinicians and trialists. The 2014 recipient was Dr Chilton Chong from Southern Breast Oncology in Victoria. Dr Chilton Chong receives The John Collins Medal from Associate Professor John Collins. ANZBCTG Annual Report

16 Study Coordinator Prize This prize acknowledges outstanding commitment to the ANZBCTG clinical trials research program by a Study Coordinator. The recipient receives one return economy class airfare to the ANZBCTG ASM, accommodation for the duration of the ASM, registration including social events and $500 towards professional development relevant to clinical trials. The ANZBCTG s Trials Coordination Department nominates an award recipient annually to the ANZBCTG Board of Directors for ratification. The 2014 recipient was Ms Rosemary Cotton from Ballarat Oncology and Haematology Services in Victoria. Professor Fran Boyle congratulates Ms Rosemary Cotton on receiving The Study Coordinator Prize. Avon Travel Grants Avon Travel Grants recognise Trial Coordinators and junior clinicians who are unable to access institutional or other funding to attend the ANZBCTG ASM. Generously provided by Avon, the Grants cover the costs of attending the ASM including return economy class airfares, accommodation for the duration of the ASM and full single registration (including social functions). The 2014 recipients were: Ms Alison Coote, Orange Health Service, NSW; Ms Anne Milton, Royal Adelaide Hospital, SA; Avon Travel Grant recipients: Ms Anne Milton, Dr Jane Parry, Mrs Jenny Gilchrist and Ms Gabrielle Howarth. Ms Gabrielle Howarth, Royal Perth Hospital, WA; Ms Jane Holt, Icon Cancer Care Wesley, QLD; Mrs Jenny Gilchrist, Macquarie University Hospital, NSW; Dr Jane Parry, Campbelltown Hospital, NSW; Mrs Kathryn Robinson, Victorian Breast & Oncology Care, VIC. ANZBCTG Discretionary Funding The ANZBCTG Scientific Advisory Committee (SAC) evaluates, selects and recommends new trial proposals to ensure the portfolio of trials conducted by the ANZBCTG are of high scientific merit and meet the requirements of the broader membership. SAC Subcommittees have been formed to encourage the participation of members of the ANZBCTG, particularly clinical investigators in all aspects of the ANZBCTG Clinical Trials Research Program. The three SAC Subcommittees include: Local Therapy, Systemic Therapy and Supportive Care. Subcommittees help refine selected proposals initiated by members of the ANZBCTG and may approve these concepts for presentation to the full SAC for consideration as future trials. The ANZBCTG provides opportunities for its members to apply for Discretionary Funding to support research concepts that have been endorsed by the SAC for progression and which align with the strategic direction of the Group. Funding for this initiative comes from public donations made to the Breast Cancer Institute of Australia, without which these important projects could not be supported. Guidelines for Discretionary Expenditure of Accumulated Funds can be accessed on the Research Section of the ANZBCTG website ( 14 ANZBCTG Annual Report

17 Discretionary Funding for Research (category 1a seed funding) awarded in 2014: Dr Elgene Lim Targeting the P53 pathway in oestrogen-receptor-positive breast cancer; Professor Sunil Lakhani Repurposing pertuzumab for adjuvant treatment of breast cancer patients with HER2-positive brain metastases; Professor Phyllis Butow Developing a patient decision aid for women with early stage breast cancer considering contralateral prophylactic mastectomy; Dr Yoland Antill Identifying the timeline and quality of life implications of madarosis in patients undergoing cytotoxic chemotherapy for breast cancer. Infrastructure Funding (category 2) awarded in 2014: Dr Peter Fox, Orange Health Service, NSW. Operations It is a pleasure to note the approval of two new institutions for participation in the ANZBCTG Clinical Trials Research Program in the reporting period, which will enable more women, particularly those located in regional areas, access to clinical trials: South West Health Care, Warrnambool, Vic; St George s Hospital, Auckland, NZ. Patient safety, privacy and welfare remain paramount to the research program. All trials are reviewed by a human research ethics committee (HREC) and notified to the appropriate regulatory authority prior to patient participation. The ANZBCTG Ethics and Regulatory Affairs (E&RA) team continues to support investigators with their preparation of ethics and governance submissions, protocol amendments, grant applications, safety reporting and site contracts. The E&RA team works closely with staff at member institutions across Australia and in New Zealand to utilise streamlined ethics review processes which allow multiple sites to accept a single ethics review from one HREC, thereby saving duplication of effort at sites and HRECs, and facilitating clinical trial activation at multiple sites simultaneously. One such initiative is Australia s National Mutual Acceptance process which is working well across sites in New South Wales, Queensland, South Australia and Victoria, with excellent support from investigators and trial coordinators, and with positive feedback received following our submissions to reviewing ethics committees. The ANZ 1301 DOMINO Decision Aid trial signals a new approach to coordinating smaller studies or substudies (refer to ANZ 1301 exploring DecisiOn MakIng about NeOadjuvant chemotherapy for operable breast cancer (DOMINO) on page 33). The framework in which this supportive care study is being managed is also new; women who participate will use an online tool to access the Decision Aid and to respond to a series of questionnaires over a 12 month period. It is anticipated that this new approach to project management and introduction of an online tool will improve efficiency and provide alternative models to meet the challenges of the changing clinical trials landscape. The DOMINO study was developed using data from two surveys of patients and breast cancer specialists about their experience with neoadjuvant systemic therapy for breast cancer. These studies demonstrated that both patients and doctors are interested in this treatment approach, and confirmed that a study is warranted to investigate ways to support those involved in the decision about neoadjuvant systemic therapy. A survey of 370 women with a history of early stage breast cancer with current or past experience taking an aromatase inhibitor was conducted in collaboration with Breast Cancer Network Australia. The survey concluded that effective treatments are needed to help women with early stage breast cancer who suffer from Aromatase Inhibitor Induced Musculoskeletal Syndrome (AIMSS) to continue their cancer treatment. Many women who suffer from AIMSS stop their breast cancer treatment due to these side effects. The results were reported at the annual San Antonio Breast Cancer Symposium in Texas, USA in December The launch of our new ecrf system for the ANZ 1401 ELIMINATE clinical trial is expected to have a positive impact on the efficiency and standardisation of data collection processes for this and future trials. The same system will be used for all new ANZBCTG led trials; real-time data entry and logic checks will help prevent data ANZBCTG Annual Report

18 entry error and reduce the number of data queries that need to be managed by staff at institutions taking part in the trial. From a central perspective the new system has potential for more rapid central and medical review of trial data, reducing the time needed to prepare for analyses, the time to publication and overall costs to conduct the trial. The ANZ 0501 LATER clinical trial examined whether or not additional treatment with an aromatase inhibitor called letrozole, commenced much later after the initial diagnosis of breast cancer, could reduce the risk of breast cancer returning in this large group of women. Recruitment ceased in March 2012 after 360 participants were randomised, due to a lower than expected rate of accrual. In October 2014, after review of pooled data, the ANZBCTG Independent Data and Safety Monitoring Committee recommended that trial follow-up cease and that the data be released for analysis, based on a lower than expected event rate. LATER data has been analysed and results will be presented at the American Society for Clinical Oncology meeting in Chicago in June this year. A record number of 10 clinical trials were open at our member institutions during the reporting period. More information about each of these trials is located on pages 18 to 33. The ANZBCTG has a communication, rather than a coordination role for one of these studies, BIG 3-13/GO28888 LORELEI, a neoadjuvant (treatment before surgery) trial that will evaluate the effect of combining letrozole and a new medication, GDC-0032, versus letrozole and placebo in postmenopausal women with hormone-sensitive, HER2-negative, operable breast cancer. A new, direct collaboration with the Nottingham Clinical Trials Unit in the United Kingdom will see the launch of the POSNOC trial. This trial aims to assess whether or not, for women with early breast cancer and metastases in one or two sentinel nodes, adjuvant systemic therapy alone is equivalent to adjuvant systemic therapy plus further axillary treatment. The POSNOC trial is supported by a project grant from the Australian National Health and Medical Research Council. During the reporting period our Trial Coordination Procedures were thoroughly reviewed and, where necessary, updated to comply with changes to clinical trials regulation and to ensure tasks are carried out appropriately, correctly and uniformly. These achievements and the expansion of our clinical trials portfolio would not have been possible without the support of our enthusiastic and experienced staff; their dedication and hard work is acknowledged. Members of many committees support the ANZBCTG by contributing their time and expertise; their commitment is greatly appreciated and is an essential component of a high quality clinical trials research program. We are thankful for the women who, by deciding to take part in our clinical trials, make a vital contribution to improving breast cancer outcomes for everyone. Summary The flavour of this year s research report is firmly in the endocrine arena, again underlying the importance in the modern era of clinical trials that address questions pertinent to specific breast cancer subtypes. While previous years have seen major advances, especially in the treatment of HER2-positive disease, the focus over the last 12 months has been on the management of ER (oestrogen-receptor)-positive disease, the long term prevention of ER-positive disease (IBIS-I) and in a niche study, the preservation of fertility in younger women undergoing chemotherapy. The adjuvant SOFT, TEXT and POEMS clinical trials in particular teach us a number of lessons very pertinent to the ANZBCTG, with congratulations up front to our own Associate Professor Prue Francis and Professor Kelly-Anne Phillips for their efforts in driving these trials on our behalf. The first is that adequately powered adjuvant trials require a sustained effort over years to decades, especially in ER-positive disease. It s fun to be involved in trials of new smart drugs with short term endpoints and it s important to do that research, but also critical to generate mature unimpeachable data about everyday medications. The second, is the importance of studying the full benefits of drugs that may be beyond the interest of the pharmaceutical companies that produced them think of the combination of GnRH analogues and tamoxifen or exemestane (SOFT and TEXT), the prolonged use of tamoxifen (ATLAS) and the fertility-protecting effect of goserelin (POEMS). The third, is 16 ANZBCTG Annual Report

19 the nuance with which many of these trials need to be examined we would not for example advocate that all younger women with ER-positive breast cancer be treated with ovarian suppression plus exemestane, but clearly some women will benefit substantially from such treatment. All of these lessons lead to a common conclusion: the vital importance of collaborative, academic, independent clinical trials groups. The pharmaceutical industry remains a critical component of the clinical trials community, and one we are privileged to work with, but there are important research questions they cannot explore. The ANZBCTG is proud of the successes in both worlds. This year was the triumph of the large adjuvant trial, while next year we expect to accrue patients to a number of smaller subtype-specific trials of new molecules, as well as a new local therapy trial. Professor John F Forbes AM Director of Research Associate Professor Nicholas Wilcken Chair, Scientific Advisory Committee Associate Professor Prue Francis Vice Chair, Scientific Advisory Committee Dr Nicholas Zdenkowski Clinical Fellow Mrs Dianne Lindsay Head of Trials Management ANZBCTG Annual Report

20 Clinical Trials Open for Participant Entry The ANZBCTG is dedicated to innovative clinical trials research designed to prevent breast cancer in women at higher risk of developing this disease and to improving outcomes for women who are diagnosed with breast cancer. Clinical trials are fundamental to identify if a treatment or treatment strategy is safe, effective and has the potential to save lives. All new medications, treatment and supportive care strategies are rigorously tested through the clinical trials process and all research conducted by the ANZBCTG is carried out to the highest ethical and regulatory standards. The ANZBCTG has coordinated 75 trials since our research group was established in More than 14,000 participants have taken part in ANZBCTG research. Our research brings together more than 700 researchers in 87 institutions throughout Australia and New Zealand. This collaboration facilitates the conduct of clinical research in institutions with a wide geographical spread and ensures the efficient sharing of knowledge, expertise and resources. The ANZBCTG enrolled 41 participants to 10 clinical trials during the reporting period. In addition we continued to collect participant follow-up data for 19 international trials. Our research, through international collaboration underpins the significant progress made to date to improve outcomes for women diagnosed with breast cancer. ANZBCTG clinical trials open to participant entry in the reporting period were: ANZ 1002 Post-operative Radiotherapy Omission in Selected Patients with Early breast Cancer Trial (PROSPECT); ANZ 1103 Study of OLAparib Clinical Effect (SOLACE); ANZ 1201 / BIG 6-11 / GBG-73 / SOLTI 1003 / CBKM12F2203 Pi3k inhibition in Her2 OverExpressing Breast cancer (NeoPHOEBE); ANZ 1202 / TRIO-022 / A (PALOMA-2); ANZ 1401 Oestrogen Lowering Intervention May Increase NeoAdjuvant Therapy Efficacy (ELIMINATE); ANZ 1402 / GBG-78 / BIG 1-13 / NSABP-B-54-I (PENELOPE B ); ANZ 1403 / BIG 3-13 / GO28888 Letrozole + GDC-0032 in estrogen REceptor positive early breast carcinoma (LORELEI) - see page 16 of the Research Report; ANZ 1404 / BIG 6-13 / AstraZeneca D081CC00006 (OlympiA); IBCSG / BIG 4-13 anti-pd-1 monoclonal antibody in AdvanCed, trastuzumab-resistant, HER2-positive breast cancer (PANACEA); ANZ 1301 exploring DecisiOn MakIng about NeOadjuvant chemotherapy for operable breast cancer (DOMINO). 18 ANZBCTG Annual Report

21 ANZ 1002 Post-operative Radiotherapy Omission in Selected Patients with Early breast Cancer Trial (PROSPECT) A single arm phase II study using magnetic resonance imaging (MRI) to select patients with early breast cancer for omission of post-operative radiotherapy. Lead International Group: ANZBCTG First ANZBCTG Participant Enrolled: 8 September 2011 ANZBCTG Study Chair: Professor Bruce Mann (Royal Melbourne Hospital) For women diagnosed with early invasive breast cancer, standard treatment often involves breast conserving surgery followed by radiotherapy to reduce the risk of breast cancer returning to that breast (local recurrence). The need for radiotherapy depends on the risk of local recurrence occurring after surgery alone. If the chance is known to be minimal, there may be no need for radiotherapy. At present however, no sizeable group of patients with minimal risk of local recurrence after surgery alone has been identified, so the vast majority of women are recommended to have radiation. The treatment is usually given as a daily dose over three to six weeks and receiving radiotherapy treatment can lead to some short and longer term side effects. PROSPECT is a pilot clinical trial which is using a new technology, breast magnetic resonance imaging (MRI), in combination with review of pathological features of the breast tumour to prospectively identify women who may be able to safely avoid radiotherapy because their risk of local recurrence is very low. PROSPECT will fundamentally examine whether the abnormalities that contribute to the likelihood of local recurrence (and hence the need for post-surgery radiotherapy treatment) can be detected by breast MRI. Samples of the tumour tissue removed during surgery will be collected to further our knowledge about breast cancer. If it is found that radiotherapy can be omitted without a significant risk of local recurrence, it could alter the management of women with early breast cancer as well as decrease costs to the health care system. This may be particularly significant for rural and remote women, who frequently choose total mastectomy (breast removal) to avoid the need to have radiotherapy treatment that requires them to be absent from home. If this phase II trial demonstrates an acceptably low rate of local recurrence, a larger, multicentre clinical trial will be conducted. The ANZBCTG has registered 139 women who have undergone pre-operative breast MRI and 61 of these women have been enrolled in PROSPECT (31 March 2015). The planned recruitment target for the PROSPECT clinical trial is 200 women. PROSPECT is supported by ANZBCTG Discretionary Funding, with support from the National Breast Cancer Foundation and Cancer Council of Victoria. Screening and recruitment increased throughout 2014, and with three ANZBCTG institutions now activated to recruit participants we look forward to further increased screening and recruitment to this important trial in Professor Bruce Mann Patient Population Female, aged >_ 50 Histologically confirmed invasive, unifocal, unilateral breast cancer <_ 20 mm pn0 by sentinel node biopsy or axillary dissection WLE >_ 2 mm margins (invasive and DCIS) Pre-op MRI* WLE: wide local excision MRI: magnetic resonance imaging * nil/minimal, mild parenchymal enchancement only R E G I S T R A T I O N standard treatment without radiotherapy ANZBCTG Annual Report

22 ANZ 1103 Study of OLAparib Clinical Effect (SOLACE) A phase I study of Olaparib, a poly ADP-ribose polymerase-1 (PARP) inhibitor, in combination with metronomic cyclophosphamide in patients with metastatic BRCA-associated cancer, triple negative breast cancer or serous ovarian cancer. Lead International Group: ANZBCTG First ANZBCTG Participant Enrolled: 17 June 2014 ANZBCTG Study Co-Chairs: Dr Chee Lee (St George Hospital) Professor Michael Friedlander (Prince of Wales Hospital) SOLACE is a phase I clinical trial for women or men who have been diagnosed with advanced BRCA-associated breast cancer, triple negative breast cancer or serous ovarian cancer. The aim of this clinical trial is to confirm the most suitable (maximum tolerated) dose of olaparib and cyclophosphamide when these drugs are given together. Olaparib is a drug which harms cancer cells by blocking DNA from repairing within the cancer cells. When DNA cannot be repaired, the cancer cells are unable to grow. Early results from treatment using olaparib have shown that people with some types of breast and ovarian cancers have shrinkage of their tumour. However, when olaparib is given with chemotherapy, it frequently results in a patient s immune system being suppressed. Cyclophosphamide is a DNA-damaging drug widely used in the treatment of breast cancer and epithelial ovarian cancer. When given orally as a low dose continuous (metronomic) therapy, it does not significantly suppress the immune system. Researchers believe that combining olaparib with metronomic cyclophosphamide might cause more damage to cancer cells than either drug alone, and increase the chance that these cancers will be effectively treated, without undue impairment of the immune system. In SOLACE, small groups of trial participants will receive olaparib and cyclophosphamide at pre-specified doses. Groups will be assessed at each dose level for side effects until the maximum tolerated doses are determined. All participants will be regularly monitored throughout treatment to evaluate side effects, to assess response rate, progression-free survival, and overall survival. If researchers are able to determine the maximum tolerated doses of olaparib and cyclophosphamide given together, and this treatment is found to be safe and effective, a larger clinical trial will be developed. Results of this research may have implications worldwide in the treatment and management of men and women with these types of breast and ovarian cancer. SOLACE is funded by ANZBCTG Discretionary Funding, with support from AstraZeneca. Seven participants have been recruited to SOLACE (31 March 2015) with approximately 23 more participants expected to join the trial by March The first four SOLACE participants were recruited at the Prince of Wales Hospital, the next three were recruited at the Royal Melbourne Hospital and recruitment will soon commence at the St George Hospital. Once the maximum tolerated dose of combined olaparib and cyclophosphamide has been confirmed, approximately 21 participants will be recruited across all three institutions. We expect to complete recruitment during the first quarter of Dr Chee Lee and Professor Michael Friedlander 20 ANZBCTG Annual Report

23 P R E - R E G I S T R A T I O N Patient Population High grade EOC Metastatic TNBC Metastatic BRCA1 or BRCA2 associated BC 1 platinum based regimen 3 prior chemotherapy regimens May be platinum sensitive or platinum resistant/refractory May have received platinum based regimen 3 prior chemotherapy regimens Prior treatment with anthracycline & taxane, adjuvant/metastatic setting * R E G I S T R A T I O N Treatment Olaparib and cyclophosphamide at assigned dose levels# for up to 8 cycles** (1 cycle = 21 days) Follow-up for up to 60 months post-registration * Protocol treatment must begin within 72 hours of registration # Cohort of 3 patients at Dose Level 1: # Cohort of 3 patients at Dose Level 2: # Cohort of 3 patients at Dose Level 3: olaparib 300 mg bd + cyclophosphamide 50 mg days 1, 3, 5 of 7 days for 21 day cycle The first 3 patients registered at Dose Level 1 will have PK assessment olaparib 300 mg bd + cyclophosphamide 50 mg days 1-5 of 7 days for 21 day cycle The first 3 patients registered at Dose Level 2 will have PK assessment olaparib 300 mg bd + cyclophosphamide 50 mg every day for 21 day cycle ** Patients receiving clinical benefit from treatment with no DLT may continue beyond Cycle 8 on maintenance chemotherapy at the discretion of the investigator. Once MTD is determined, extension cohort patients will be registered at the MTD. If MTD is Dose Level 3 AND extension cohort patients complete 6 cycles without dose reduction, extension cohort patients will be considered for treatment at olaparib 300 mg bd days 1-7; no olaparib days 8-14; olaparib 300 mg bd days 15-21; cyclophosphamide 50 mg days 1-21 (21 day cycle). BC: Breast Cancer BRCA: Breast Cancer Gene DLT: Dose Limiting Toxicity EOC: Epithelial Ovarian Cancer MTD: Maximum Tolerated Dose PK: Pharmacokinetics TNBC: Triple Negative Breast Cancer ANZBCTG Annual Report

24 ANZ 1201 / BIG 6-11 / GBG-73 / SOLTI 1003 / CBKM12F2203 Pi3k inhibition in Her2 OverExpressing Breast cancer (NeoPHOEBE) A phase II, randomized, parallel cohort, two stage, double blind, placebo-controlled study of neoadjuvant trastuzumab versus trastuzumab + BKM120 in combination with weekly paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer. Lead International Group: Breast International Group (BIG) First ANZBCTG Participant Enrolled: 26 August 2014 ANZBCTG Study Chair: Associate Professor Sherene Loi (Peter MacCallum Cancer Centre) Neoadjuvant therapy (treatment before surgery) aims to shrink the breast cancer in size to increase the chance of breast conserving surgery and to monitor the effect of the chemotherapy treatment on the tumour. To study the breast cancer s response to the treatment before surgery, biopsies can be taken and analysed, which may identify tumour biomarkers to help researchers distinguish the types of tumours which are most likely to benefit from certain chemotherapy treatments. Buparlisib is a new medicine that affects the function of a protein called PI3K, and may therefore slow the growth of breast cancer. Research shows that Buparlisib acts on breast cancers which have specific markers on the surface called HER2. The NeoPHOEBE clinical trial was developed to investigate giving this new medicine as part of neoadjuvant therapy to determine the effectiveness of Buparlisib and the benefit of adding the new drug to standard treatment for women diagnosed with HER2-positive early breast cancer. Standard treatment for HER2-positive breast cancer usually includes a combination of chemotherapy (eg: paclitaxel) and trastuzumab given either before or after surgery. Participants in the NeoPHOEBE clinical trial received neoadjuvant therapy for 18 weeks before breast surgery. In addition to standard treatment, participants were randomly assigned to receive either a Buparlisib capsule or a placebo capsule. Half of the study participants received Buparlisib and half received a placebo. Participants will be closely monitored and followed up by their doctor following surgery and may be offered further treatment according to local standard of care for this type of breast cancer. It was anticipated that the results of this study would help determine the effectiveness of Buparlisib and improve outcomes for future patients diagnosed with HER2-positive early breast cancer. NeoPHOEBE is an international clinical trial conducted with the German Breast Group (GBG), the Spanish research group (SOLTI), the Breast International Group (BIG), and Novartis. Following review of safety data by the Independent Data Monitoring Committee in October 2014 it was recommended that recruitment be placed on hold. In January 2015, the international sponsor decided to stop the study due to recruitment challenges and the evolving landscape in the HER2+ neo-adjuvant setting and the study was closed. The ANZBCTG enrolled one of the 50 women participating in this trial internationally. I would like to thank the investigators and women who supported this trial. Associate Professor Sherene Loi 22 ANZBCTG Annual Report

25 Patient Population Stratification 6 Weeks 12 Weeks Trastuzumab Primary breast tumour >2 cm HER2 positive PIK3CA wild-type or mutant* ER positive vs negative R A N D O M I S A T I O N Trastuzumab + Placebo Trastuzumab + BKM120 + Paclitaxel + Placebo Trastuzumab + Paclitaxel + S U R G E R Y BKM120 * There will be two study cohorts - PIK3CA mutant and PIK3CA wild-type. The study will be conducted separately in each cohort. Trastuzumab: 4 mg/kg then 2 mg/kg weekly BKM120: 100 mg daily Paclitaxel: 80 mg/m 2 weekly Placebo: daily ANZBCTG Annual Report

26 ANZ 1202 / TRIO-022 / A (PALOMA-2) A randomised, multicentre, double blind phase 3 study of PD (oral CDK 4/6 inhibitor) plus letrozole versus placebo plus letrozole for the treatment of postmenopausal women with ER (+), HER2 (-) breast cancer who have not received any prior systemic anti-cancer treatment for advanced disease. Lead International Group: First ANZBCTG Participant Enrolled: 2 December 2013 ANZBCTG Study Chair: Translational Research In Oncology (TRIO) Dr Janine Lombard (Calvary Mater Newcastle) The PALOMA-2 trial closed to recruitment in June The ANZBCTG enrolled 20 of the 666 women participating in this trial internationally. Letrozole is a standard treatment option for postmenopausal women with breast cancer that is hormone-sensitive and has returned or spread to other areas of the body (advanced or metastatic breast cancer). The PALOMA-2 trial aims to determine if giving letrozole together with a new drug, palbociclib (PD , an oral CDK 4/6 inhibitor), is more effective than letrozole alone. The PALOMA-2 trial opened following the reporting of interim data from a phase 2 clinical trial at the San Antonio Breast Cancer Symposium, an international breast cancer conference, in December PALOMA-1 involved a small number of women with hormone-sensitive advanced breast cancer who were given palbociclib with letrozole. Palbociclib works differently to letrozole, by interfering with the cancer cell s growth cycle. Researchers found that the combination of palbociclib and letrozole controlled the spread of breast cancer longer than when letrozole was administered alone. PALOMA-2 is a larger, international phase 3 clinical trial that will further evaluate the effectiveness and safety of palbociclib and letrozole in combination and is suitable for women with advanced breast cancer that is sensitive to the hormone oestrogen (ER-positive) and which cannot be treated with curative intent by surgery or radiation therapy. To take part in this clinical trial women must not have received any other treatment for advanced breast cancer. Letrozole will be given to all trial participants. In addition, women will receive either the new drug (palbociclib) or a placebo. Researchers are using a placebo in this study to confirm whether the two drugs used together are more beneficial than treatment with letrozole alone. PALOMA-2 is an international clinical trial conducted with Translational Research In Oncology (TRIO) and Pfizer. During the past year significant progress has been made with accelerated approval granted by the U.S. Food and Drug Administration for the treatment of postmenopausal women with ER-positive, HER2-negative advanced breast cancer with palbociclib in combination with letrozole in the United States of America. Continued approval may be contingent upon verification of clinical benefit in on-going trials, including PALOMA-2. We are now preparing PALOMA-2 for an important interim analysis and thank all investigators and research teams for their efforts to submit timely data for this important trial. The results of PALOMA-3, a trial with an anti-estrogen and palbociclib in women with progression of metastatic breast cancer after prior endocrine therapy, will be presented at the American Society of Clinical Oncology (ASCO) in mid These trial results are eagerly awaited and will also inform us further of the activity of palbociclib in women with advanced breast cancer. Dr Janine Lombard 24 ANZBCTG Annual Report

27 Patient Population Stratification Postmenopausal women >_ 18 years ER positive/her2 negative breast cancer Locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent, chemotherapy not indicated, measurable and/or non-measurable disease No prior systemic anticancer treatment for advanced disease Disease-free interval Previous therapy Disease site R A N D O M I S A T I O N 2/3 Letrozole + Palbociclib* 1/3 Letrozole + Placebo* # PD or UT or CW Letrozole: Palbociclib (PD ): Placebo: 2.5 mg daily 125 mg daily 21 days on/7 days off 21 days on/7 days off * Treatment to commence within 4 business days after randomisation. # Treatment will continue until progressive disease (PD), unacceptable toxicity (UT), or participant s consent is withdrawn (CW). ANZBCTG Annual Report

28 ANZ 1401 Oestrogen Lowering Intervention May Increase NeoAdjuvant Therapy Efficacy (ELIMINATE) Randomised phase II trial of neoadjuvant chemotherapy +/- concurrent aromatase inhibitor endocrine therapy to down-stage large oestrogen receptor positive breast cancer. Lead International Group: First ANZBCTG Participant Enrolled: ANZBCTG Study Co-Chairs: ANZBCTG Pending Dr Nick Murray (Royal Adelaide Hospital) Associate Professor Prue Francis (Peter MacCallum Cancer Centre) Neoadjuvant therapy (treatment before surgery) aims to shrink the breast cancer in size to increase the chance of breast conserving surgery and to monitor the effect of treatment on the tumour. The ELIMINATE clinical trial is investigating whether combining two breast cancer treatments before surgery is more effective than one alone in women diagnosed with large oestrogen receptor-positive breast cancer. These two treatments, chemotherapy and hormone treatment, are usually given one after the other. Oestrogen receptor-positive breast cancer grows in the presence of the hormone oestrogen. An enzyme called aromatase is responsible for the production of oestrogen in both pre and postmenopausal women, while the functioning ovaries in premenopausal women also produce oestrogen. Lowering or eliminating oestrogen using hormone treatments that block the aromatase enzyme and stop the ovaries from producing oestrogen are an effective way of treating breast cancer that is hormone-sensitive. An aromatase inhibitor called letrozole blocks the aromatase enzyme from producing oestrogen making it an effective hormone therapy for postmenopausal women. Goserelin is a medication that causes a temporary menopause, preventing the ovaries from producing oestrogen which, when combined with an aromatase inhibitor like letrozole, is an effective hormone therapy for premenopausal women. The ELIMINATE clinical trial will investigate if giving neoadjuvant hormone therapy and chemotherapy at the same time is more effective than neoadjuvant chemotherapy alone at shrinking the breast cancer before surgery. All participants in the ELIMINATE clinical trial will receive standard neoadjuvant chemotherapy for between 18 and 24 weeks before surgery. Two in every three participants will be randomly assigned to receive hormone therapy in addition to standard neoadjuvant chemotherapy. Participants will be closely monitored by their doctor during neoadjuvant treatment and, after breast surgery, may be offered further treatment according to local standard of care. It is hoped that the results of this study will help determine the effectiveness of hormone therapy in combination with standard chemotherapy given before surgery and improve treatment choices and outcomes for women diagnosed with oestrogen receptor-positive breast cancer in the future. ELIMINATE is supported by an NHMRC Project Grant G The first hospital to open for participant recruitment was activated in Melbourne in March We plan to recruit 123 women to the ELIMINATE trial over approximately 42 months at more than 20 hospitals across Australia and New Zealand. However, we hope that recruitment will occur more quickly so that an answer to this important research question can be obtained sooner and provide more treatment options for women diagnosed with early breast cancer. Dr Nick Murray and Associate Professor Prue Francis 26 ANZBCTG Annual Report

29 Patient Population Intact clinical Stage 2 or 3, Grade 2 or 3 invasive breast cancer for future resection ER positive, HER2 negative ct2-4 (> 20 mm) Stratification Menopausal status Clinical Stage 2 vs Stage 3 R A N D O M I S A T I O N 2 1 Chemotherapy + Letrozole (+ Goserelin*) Chemotherapy S U R G E R Y Routine care adjuvant endocrine therapy and radiotherapy Chemotherapy: 18 weeks anthracycline + taxane Letrozole: 2.5mg per day following randomisation until surgery for postmenopausal women 2.5mg per day starting 4 weeks after goserelin for pre- and peri-menopausal women *Goserelin: for pre- and peri-menopausal women only. Inject following randomisation and repeat every 4 weeks until surgery Imaging: Baseline (mammogram, ipsilateral breast and axillary ultrasound and breast MRI); MRI repeated after completing chemotherapy. Research core biopsies: Baseline (including tumour marking); prior to chemotherapy cycle 3 (or between week 6 & 7 if weekly chemotherapy); at surgery from resected tumour. Research blood samples: Baseline; prior to chemotherapy cycle 3 (or between week 6 & 7 if weekly chemotherapy); after completion of chemotherapy; after surgery. ANZBCTG Annual Report

30 ANZ 1402 / GBG-78 / BIG 1-13 / NSABP-B-54-I (PENELOPE B ) Phase III study evaluating palbociclib (PD ), a Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor in patients with hormone-receptor-positive, HER2-normal primary breast cancer with high relapse risk after neoadjuvant chemotherapy. Lead International Group: German Breast Group (GBG) First ANZBCTG Participant Enrolled: 12 January 2015 ANZBCTG Study Chair: Associate Professor Nicole McCarthy (Icon Cancer Care Wesley) Neoadjuvant (before surgery) chemotherapy can substantially reduce the size of a primary breast tumour to allow for breast conserving surgery and surgery for tumours that were inoperable before chemotherapy. Women who receive neoadjuvant chemotherapy followed by surgery and who have some cancer remaining in the surgically removed tissue have a higher than average risk of the cancer coming back (relapse). Standard treatment after surgery for hormone receptor (HR)-positive and HER2-normal (also known as HER2-negative) breast cancer usually includes at least five years of hormone (endocrine) therapy. The PENELOPE B clinical trial is designed to evaluate whether adding one year of treatment with a new medication called palbociclib (PD ) to standard hormone therapy will improve outcomes for women with breast cancer that is HR-positive and HER2-normal. The trial drug palbociclib belongs to a group of drugs called Cyclin Dependent Kinase (CDK) inhibitors. Palbociclib blocks CDK4 and CDK6, which stops certain processes that cause cancer cells to grow. It appears to be most effective against HR-positive, HER2-normal breast cancer. In the PENELOPE B clinical trial women will receive hormone treatment and will be randomly assigned to receive either palbociclib or placebo for 13 cycles (1 capsule daily days 1-21, no capsule days 22-28). Half of the trial participants will be given palbociclib, and half will be given placebo. Participants will be closely monitored by their doctor during and after trial treatment is completed. Blood and tumour tissue samples will be collected to help researchers understand why some trial participants may experience a greater benefit from the trial treatment compared with others. Planned analysis of these samples may also help explain why some trial participants experience more side effects. PENELOPE B is an international trial led by the German Breast Group (GBG) that will involve 1,100 participants in 13 countries. The ANZBCTG has enrolled two of the 84 women participating in this trial internationally (31 March 2015). Eight hospitals in Australia are currently open for participant entry to the PENELOPE B trial with a further seven institutions preparing to activate this trial. Investigators and their research teams are making an important contribution to this global clinical trial, with more than 165 sites open and patients now recruited in four countries. It is anticipated that a recent update to the protocol will help increase patient enrolment. Associate Professor Nicole McCarthy 28 ANZBCTG Annual Report

31 Patient Population Stratification S U R G E R Y HR positive/her2 normal primary invasive breast cancer At least 16 weeks neoadjuvant chemotherapy completed (containing 6 weeks taxane) No pcr CPS-EG score 3 or 2 and ypn+ No prior treatment with any CDK 4/6 inhibitor Histological lymph node status at surgery Age at first diagnosis Ki-67 Global region of participating site Risk status * R A N D O M I S A T I O N 1:1 Palbociclib x 13 cycles + ET Placebo x 13 cycles + ET Palbociclib (PD ): Placebo: ET: CPS-EG score: 125 mg daily 21 days on/7days off x 13 cycles 21 days on/7days off x 13 cycles standard of care endocrine therapy: tamoxifen, goserelin + tamoxifen, anastrozole or letrozole clinical pathologic staging system incorporating pre and post neoadjuvant treatment stage, ER and grade *Randomisation within 16 weeks of surgery or within 10 weeks from completing radiotherapy (whichever occurs last) ANZBCTG Annual Report

32 ANZ 1404 / BIG 6-13 / AstraZeneca D081CC00006 (OlympiA) A randomised, double blind, parallel group, placebo-controlled multi-center phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA 1/2 mutations and high risk HER2-negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. Lead International Group: First ANZBCTG Participant Enrolled: ANZBCTG Study Chair: Breast International Group (BIG) Pending Professor Kelly-Anne Phillips (Peter MacCallum Cancer Centre) OlympiA is an international trial which will enrol 1,320 participants in 23 countries. It is open to both women and men diagnosed with triple-negative breast cancer provided they have an inherited BRCA1 or BRCA2 gene mutation. About 15% of breast cancers are a type which is called triple-negative breast cancer. While many of these cancers are cured with currently available standard treatments (which can include breast surgery, chemotherapy and radiotherapy), some are not cured, so new treatments are needed. A small proportion of individuals diagnosed with triple-negative breast cancer inherited a BRCA1 or BRCA2 gene mutation and are a carrier of one abnormal copy of the gene. Our bodies are made up of billions of cells that have two copies of every gene. The DNA in the genes in our cells acts as an instruction book telling our cells how to make proteins. In normal cells the BRCA1 and BRCA2 genes make proteins that help to repair DNA. An inherited mutation in a BRCA1 or BRCA2 gene means that one of the copies of the gene is not working but that the other copy can maintain the normal function. It is when the second copy of the BRCA1 or BRCA2 gene acquires a mutation that both copies are now non-functional and the wrong protein is made. With two non-functional copies making the wrong protein, the ability of the cell to repair DNA damage is affected. If DNA damage cannot be repaired, but the cell remains alive, the cell may become cancerous by growing uncontrollably and forming a tumour mass. The OlympiA clinical trial is investigating whether taking olaparib tablets twice a day for 12 months can reduce the risk of breast cancer coming back after all standard anticancer treatments have been completed. Participants will have a 50:50 chance (randomly allocated) of receiving either olaparib or a placebo. They will be reviewed regularly to ensure their safety. Follow-up of participants will continue for 10 years after the last person is enrolled. This trial is being conducted in partnership with the Breast International Group (BIG) and AstraZeneca. It is hoped that the trial will show that olaparib improves the curability of patients with triple-negative breast cancer and inherited BRCA1 or BRCA2 mutations, which may result in a new standard treatment for these breast cancer patients. It is great news for Australian patients that 15 ANZBCTG member hospitals will be participating in this innovative study. It is anticipated that the first Australian site will open OlympiA during April 2015, with other hospitals coming on board soon afterwards. Professor Kelly-Anne Phillips 30 ANZBCTG Annual Report

33 Patient Population Stratification Female or male 18 years Documented gbrca1 or gbrca2 mutation Non-metastatic primary TNBC Completed definitive local treatment and neoadjuvant or adjuvant chemotherapy Post neoadjuvant / adjuvant chemotherapy Prior platinum therapy for current breast cancer Yes/No Post neoadjuvant chemotherapy Non-pathCR Post adjuvant chemotherapy N+ (any tumour size) or N- (primary tumour >2cm) * R A N D O M I S A T I O N 1:1 Olaparib 52 weeks Placebo 52 weeks * Randomisation 8 weeks since all surgery / chemotherapy / adjuvant radiotherapy completed (whichever is last) Chemotherapy 6 cycles anthracyclines and/or taxanes gbrca: germline BRCA1 or BRCA2 mutation TNBC: triple-negative breast cancer Olaparib: 300mg (2 x 150mg tablets) twice daily for up to 52 weeks Placebo: 2 tablets twice daily for up to 52 weeks Non-pathCR: pathological complete response not achieved (breast and/or lymph nodes) ANZBCTG Annual Report

34 IBCSG / BIG 4-13 anti-pd-1 monoclonal antibody in AdvanCed, trastuzumab-resistant, HER2-positive breast cancer (PANACEA) A phase Ib/II trial evaluating the efficacy of MK3475, an anti-pd1 monoclonal antibody, and trastuzumab in patients with trastuzumab-resistant, HER2 overexpressing metastatic breast cancers. Lead International Group: First ANZBCTG Participant Enrolled: ANZBCTG Study Chair: International Breast Cancer Study Group (IBCSG) Pending Associate Professor Sherene Loi (Peter MacCallum Cancer Centre) PANACEA is a phase I/II clinical trial for women who have been diagnosed with advanced HER2-positive breast cancer. The standard treatment for HER2-positive breast cancer that has progressed is to continue treatment with trastuzumab and to add another type of therapy or chemotherapy. The aim of this clinical trial is to find out the most suitable (maximum tolerated) dose of MK-3475 and trastuzumab when these drugs are used together and to assess if their combined use is an effective treatment. Trastuzumab and MK-3475 are monoclonal antibodies. Naturally occurring antibodies are made by the body to protect against infection by attacking foreign substances. A monoclonal antibody is a laboratory-produced antibody designed to attach to cancer cells and mimic the antibodies that are naturally produced as part of the immune system s response to germs, vaccines, and other invaders. MK-3475 is a monoclonal antibody that works against a protein called PD-1 on the surface of the cancer cells. It is thought that cancer cells with increased levels of PD-1 avoid detection by the body s natural immune system. Trastuzumab and MK-3475 are being given together to see if they can decrease the level of PD-1 in breast cancer and allow the body s immune system to identify and work against the cancer cells. To ensure that PANACEA is a suitable option for patients, the amount of PD-1 and HER2 receptors that are present in metastatic breast cancer tissue will be tested before entry to the trial. Although trastuzumab and MK-3475 have been given individually to cancer patients, this is the first study that will test the combination of the two drugs. Initially, a small number of trial participants will receive both drugs at pre-specified doses and study doctors will assess any side effects until the maximum tolerated dose is determined. All participants will be regularly monitored throughout treatment to evaluate side effects, treatment tolerability and effectiveness of this combination therapy. Up to 46 patients from five countries are expected to be enrolled in PANACEA over a period of 18 months. In Australia we expect that up to 10 patients will take part. It is hoped that this trial will provide evidence of a new treatment option for women diagnosed with advanced breast cancer that is HER2-positive. PANACEA is a very important, small, early phase clinical trial which will involve up to 10 institutions in Europe and Australia. Given the recent listing of pembrolizumab by the Pharmaceutical Benefits Advisory Committee for the treatment of advanced melanoma in adults we hope that the PANACEA clinical trial will demonstrate a similar clinical benefit for women diagnosed with advanced HER2-positive breast cancer. Associate Professor Sherene Loi Patient Population Female 18 years Unresectable loco-regional, or metastatic histologically confirmed breast cancer Locally confirmed HER2-positivity Demonstrated progression on trastuzumab LVEF 55% ECOG 0-1 S C R E E N I N G Metastatic Biopsy: Centrally confirmed HER2-positive Centrally confirmed PD-L1 expression E N R O L M E N T MK mg/kg, 2mg/kg or 10mg/kg + Trastuzumab 6mg/kg Every 3 weeks for a maximum of 24 months 32 ANZBCTG Annual Report

35 ANZ 1301 exploring DecisiOn MakIng about NeOadjuvant chemotherapy for operable breast cancer (DOMINO) A phase II study evaluating a decision aid for women considering neoadjuvant systemic therapy for operable invasive breast cancer. Lead International Group: First ANZBCTG Participant Enrolled: ANZBCTG Study Chair: ANZBCTG Pending Dr Nicholas Zdenkowski (The Breast & Endocrine Centre) With an increasing number of treatment options available for early breast cancer, patients may be asked to make complex decisions about their treatment at a time when they are dealing with the stress of a breast cancer diagnosis. Neoadjuvant systemic therapy (chemo- or endocrine therapy before surgery) is an option that may be preferred by some women. A Decision Aid may improve patients ability to participate in the decision-making process and to make an informed decision based on their own priorities. The ANZ 1301 DOMINO study aims to find out if a Decision Aid, developed to give women information about adjuvant and neoadjuvant treatment for breast cancer, is useful in helping them to make a decision about their treatment. The content of the Decision Aid is based on the DOMINO survey results (ANZ 1301 DOMINO Project 1: Exploring decision making about neoadjuvant chemotherapy for women with operable breast cancer), including information delivery preferences and factors considered by patients to be relevant to their decision. Participants will access the Decision Aid and complete a series of questionnaires online over a 12 month period, and computer and internet access are required. A selected number of participants who consent to a telephone interview will be contacted by researchers to discuss individual women s experiences using the Decision Aid. Investigators will also be contacted via an online survey and telephone interview to discuss their experience with the Decision Aid its acceptability and feasibility of use in routine clinical practice. This study is supported by a grant from The HCF Health and Medical Research Foundation, is conducted by the ANZBCTG and will open for participant entry at four Australian hospitals. The study aims to enrol 50 women. Previous work within this program of research has involved interviews with patients and a survey of Australian and New Zealand clinicians. Both groups expressed interest in neoadjuvant therapy for treatment of early stage breast cancer, and in using a patient decision aid for women who are given this option. We aim to guide women to make a decision based on their personal priorities and values. We will measure the effect of the decision aid on their decision-making process, knowledge and satisfaction. Dr Nicholas Zdenkowski Patient Population Operable, invasive breast cancer Tumour size 2cm, N0-2 NAST to be considered R E G I S T R A T I O N Decision Aid (pre-da assessment) Telephone Interview* Treatment Decision: NAST # OR Adjuvant Therapy post-surgery ** Investigator-reported acceptability and feasibility ^ * 10 participants selected at random # Questionnaires: after Treatment Decision, after CTx (before surgery) and 12 months after registration ** Questionnaires: after Treatment Decision, after surgery (before adjuvant treatment) and 12 months after registration ^ After the last patient is registered CTx: DA: NAST: Chemotherapy Decision Aid Neoadjuvant Systemic Therapy * ANZBCTG Annual Report

36 Clinical Trials Accrual Completed Participant Follow-up Continuing The trials listed below have completed participant enrolment, which means the target sample size has been achieved and the trial has entered a follow-up phase. During this period planned trial analyses will be completed and the results published in peer reviewed medical journals. Please refer to the Publications list on page 70. Opened by the ANZBCTG Participant accrual completed ANZ 1102 / BIG 4-11 / BO25126 / TOC4939G (APHINITY): A randomised multicentre, double-blind, placebo-controlled comparison of chemotherapy plus trastuzumab plus placebo versus chemotherapy plus trastuzumab plus pertuzumab as adjuvant therapy in patients with operable HER2-positive primary breast cancer. December 2011 July 2013 IBCSG (Maintenance Chemotherapy): Low-dose cytotoxics as anti-angiogenesis treatment following adjuvant induction chemotherapy for patients with ER-negative and PgR-negative breast cancer. November 2000 December 2012 IBCSG / BIG 1-07 (SOLE): A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following four to six years of prior adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, node-positive early stage breast cancer. ANZ 0501 (LATER): A randomised trial of letrozole plus usual care versus usual care without letrozole to prevent new breast cancer events in postmenopausal women who have completed a minimum of four years of adjuvant endocrine therapy for early, hormone-responsive breast cancer more than one year previous, and who are disease-free at trial entry. ANZ 02P2 / IBIS-II (Prevention and DCIS): International multicentre trials of anastrozole versus placebo in postmenopausal women at increased risk of breast cancer and tamoxifen versus anastrozole in postmenopausal women with hormone-sensitive DCIS. ANZ 0802 / TRIO-CIRG 012: A multicentre, multinational, randomised, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer. IBCSG / SWOG S0230 (POEMS): A phase III trial of LHRH analogue administration during chemotherapy to reduce ovarian failure following standard adjuvant chemotherapy in early stage, hormone receptor-negative breast cancer. IBCSG / BIG 3-02 (TEXT): A phase III trial evaluating the role of exemestane plus GnRH analogue as adjuvant therapy for premenopausal women with endocrine-responsive breast cancer. March 2008 August 2012 April 2007 March 2012 June 2005 February 2012 October 2009 December 2011 April 2006 June 2011 May 2004 March ANZBCTG Annual Report

37 Opened by the ANZBCTG Participant accrual completed ANZ 0901 (TAILORx): A phase III, multicentre, multinational, randomised trial of adjuvant chemotherapy plus hormone treatment versus adjuvant hormone treatment alone for patients with previously resected, axillary node-negative, invasive breast cancer with various levels of risk for recurrence. October 2009 October 2010 ANZ 0702 / BIG 2-06 (ALTTO): A randomised, multicentre, open-label phase III study of adjuvant lapatinib, trastuzumab, their sequence and their combination, in patients with HER2/ErbB2-positive primary breast cancer. IBCSG / BIG 2-02 (SOFT): A phase III trial evaluating the role of ovarian function suppression and the role of exemestane as adjuvant therapies for premenopausal women with endocrine-responsive breast cancer. June 2007 July 2010 May 2004 June 2010 IBCSG 23-01: A randomised trial of axillary dissection versus no axillary dissection for patients with clinically node-negative breast cancer and micrometastases in the sentinel node. June 2005 February 2010 IBCSG / BIG 1-02 / NSABP Trial B-37: A randomised clinical trial of adjuvant chemotherapy for radically resected loco-regional relapse of breast cancer. July 2003 January 2010 IBCSG / BIG 4-02 (PERCHE): A phase III trial evaluating the role of chemotherapy as adjuvant therapy for premenopausal women with endocrine responsive breast cancer who receive endocrine therapy. ANZ 9602 (ATLAS): Adjuvant tamoxifen longer against shorter clinical trial in early breast cancer. May 2004 December 2006 November 1995 March 2005 ANZ 0101 / BIG 1-01 / IBCSG / B016348F (HERA): A randomised three-arm multicentre comparison of one year and two years of Herceptin, versus no Herceptin in women with HER2-positive primary breast cancer who have completed adjuvant chemotherapy. December 2001 January 2005 IBCSG / BIG 1-98: A phase III study to evaluate letrozole as adjuvant endocrine therapy for postmenopausal women with receptor (ER and/or PgR) positive tumours. October 1999 May 2003 ANZ 92P1 / IBIS-I: A study to determine whether tamoxifen is effective in reducing the incidence of breast cancer in women at high risk of developing breast cancer. This is a prospective double-blind placebo controlled trial. April 1992 March 2001 ANZ 9801 (ATAC): A randomised double-blind trial comparing Arimidex alone with Nolvadex alone with Arimidex and Nolvadex in combination, as adjuvant treatment in postmenopausal women with breast cancer. (Follow-up of participants is by means of the LATTE protocol) April 1998 June 1999 ANZBCTG Annual Report

38 Communication Report Ms Anna Fitzgerald It is interesting to see the changes that have occurred in communications over the last 10 years and the way organisations have adopted new technologies and different ways of communicating. The ANZBCTG has made significant inroads in keeping up to date with these business and consumer trends and expectations, over the last four years Projects This year saw the launch of our new Annual Scientific Meeting (ASM) website, which provides a platform for all information relating to the yearly conference such as registration, program, sponsors and speakers. This is the 37th year of the ASM and understandably, the online content required to host such an event has grown over the years. The ASM website can accommodate not only existing content but is also flexible for future needs. In addition to conference and registration information, online application and nomination forms for ANZBCTG Awards were also available on the ASM website. As a leading breast cancer clinical trials research organisation, the ANZBCTG has played a significant role in the development of improved treatment and prevention strategies for women diagnosed or at risk of this disease for almost four decades. To promote this work, to enhance the understanding of breast cancer clinical trials and to promote the ANZBCTG awards available to our members, several brochures were produced in the reporting period - About the ANZBCTG, What Are Breast Cancer Clinical Trials and The ANZBCTG Awards Program. The brochures are available on our website at or copies can be ordered free of charge by contacting enquiries@anzbctg.org. Search engine optimisation has been a priority area for ANZBCTG communications, to help grow our online presence and brand awareness, and to boost fundraising campaigns. This is an ongoing website project and we have already seen good results in our search rankings. IMPACT Improving Participation and Advocacy for Clinical Trials is an ANZBCTG consumer initiative. Membership is open to anyone who has an interest in breast cancer clinical trials and it aims to provide members with reliable up to date information about this important research so that they may become effective advocates for clinical trials among their own networks. An important component to IMPACT is to recognise the participation of women in clinical trials and acknowledge the contribution they have made to breast cancer prevention and improved treatments. There are approximately 1,600 members of IMPACT from Australia and New Zealand who receive regular newsletters about the ANZBCTG s activities. A formal IMPACT Communications Plan has been developed, which supports the overall communication goals of the Group and aims to provide direction and a timetable for how we will engage with IMPACT members who are interested in learning more about our research. This includes participants in the IMPACT Advocate Program, which is held during the ASM each year. For more information about IMPACT see the Consumer Advisory Panel Report on page ANZBCTG Annual Report

39 Communications Plan During the reporting period, the ANZBCTG Board of Directors approved a new Communications Plan for which supports the priorities and the goals in the Group s Strategic Plan. The Communications Plan aims to build on the success and the activities undertaken in the previous period and our communication goals are: To develop a Communication Working Group that will provide strategic advice on future communication opportunities; To promote the activities of, and the link between, the ANZBCTG and BCIA to all stakeholders; To develop innovative communication projects to build on our existing communications to all stakeholders, particularly members; To promulgate relationships with other breast cancer and/or research organisations and develop a program of engagement with leaders in the community, government and pharma; To optimise the ANZBCTG and BCIA website to help promote fundraising and research activities, and brand awareness; To develop a policy on the promotion of the ANZBCTG and its activities for all ANZBCTG members, position holders and representatives that acknowledges and promotes the ANZBCTG as a leading breast cancer clinical trials research organisation; To develop and implement a Communication Plan for the IMPACT Program, which aims to increase the awareness of the importance of breast cancer clinical trials and women s participation in this research; To develop consumer education materials about ANZBCTG activities and clinical trials research so that IMPACT members, particularly participants in the IMPACT Advocate Program, may be effective advocates for this research in the community and within their own networks; To support staff in their daily activities through the consistent implementation of policies and procedures, particularly in relation to style guidelines; To identify opportunities for external media coverage across all traditional and digital media platforms, which demonstrates the impact and relevance of ANZBCTG s research on improved patient care and more efficient use of health funding; To maintain a dynamic branding strategy across all communication collateral, which visually represents the ANZBCTG s identity and values; To encourage sponsorship and donations to support the mission of the ANZBCTG and maximise fundraising opportunities. I look forward to working with our staff, ANZBCTG Members, and all stakeholders on projects that support these goals and enhance the reputation and awareness of the ANZBCTG. Anna Fitzgerald Communications Manager ANZBCTG Annual Report

40 Consumer Advisory Panel Report Ms Leonie Young The ANZBCTG Consumer Advisory Panel (CAP) was founded in 1994 and is made up of a team of eight committed volunteers from Australia and New Zealand, who provide the ANZBCTG with consumer representation across a wide range of research activities. CAP members are actively involved in all research undertaken by the ANZBCTG, from clinical trial concept and development, through to implementation, recruitment, and follow-up. Each member of CAP has experienced breast cancer and have helped spread the word about the importance of clinical trials research in fundraising and awareness campaigns promoted by the BCIA and the ANZBCTG. Role Two CAP members are members of the ANZBCTG Scientific Advisory Committee (SAC) and each CAP member is a member of one of the SAC Subcommittees. This ensures the perspective of women who have experienced breast cancer is represented. The CAP meets approximately three times throughout the year combining face to face contact and teleconferencing. Face to face meetings include an education component as a means of maintaining the level of understanding required to fulfil their roles. CAP members are not necessarily expected to have specific expertise about the science or merits of a trial, however their understanding of the research process is vital. Accordingly, in addition to education sessions provided at meetings, each individual member undertakes related training, attends workshops, and scientific meetings to maintain a strong knowledge base. Members are Associate Investigators on funding applications to support clinical trials. One of their key roles within the research team, is to provide the perspective of someone who has been through a similar or related experience. An important requirement is to review Patient Information and Consent Forms and other communications provided to trial participants. This helps to ensure materials are clear and understandable for potential participants, to enable them to make informed decisions. Collaboration I am a member of and the current Chair of the Clinical Trials Consumer Network (CTCN), which includes representatives from the 13 other Cancer Cooperative Trials Groups (CCTGs). This network meets regularly to share information and strategies useful for consumers who participate in this specialised area of consumer representation. It provides a valuable learning tool for all, particularly those who are new to this role, and mentoring is provided by those who are more experienced. Peer support within the CTCN is invaluable and since its inception in 2011, great progress has been achieved. In the long term it is hoped this will translate into greater community awareness, increased recruitment to clinical trials, and better research funding. Individual CAP members continue to collaborate with other key breast cancer and cancer organisations, bringing an informed and comprehensive perspective to the CAP and their input into the ANZBCTG research program. For a number of years for example, CAP has collaborated with the Consumer Advisory Panel of the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. The aim is to build capacity within both groups and similar relationships are being developed between members of other CCTGs. 38 ANZBCTG Annual Report

41 IMPACT IMPACT (Improving Participation and Advocacy for Clinical Trials) began in 2001 and aims to recognise the important contributions made by women to breast cancer clinical trials research, increase participation to breast cancer clinical trials research, and lobby for increased infrastructure funding through community education. In 2006, the IMPACT Advocate Program was introduced, providing an even broader scope to educate the community. This Program offers a unique opportunity for a select group of women to enhance their knowledge and understanding of breast cancer clinical trial research, by attending the ANZBCTG s Annual Scientific Meeting (ASM). Participants attend daily tutorial sessions which provide an invaluable opportunity to discuss the conference presentations with like-minded advocates and have their questions answered by researchers who are experts in their field. CAP members play an important role in the IMPACT Advocate Program in assisting to facilitate the program and mentoring participants by supporting and guiding them through the ASM. Feedback from past programs identified that information focusing on an epidemiology perspective would assist Advocate Program participants to better understand the scientific sessions. We were honoured to have Professor Alan Coates AM facilitate this introductory workshop at the ASM in Wellington, New Zealand, in The 2014 Advocates included consumers from Australia and New Zealand, representatives from other consumer breast cancer organisations, as well as past IMPACT Program participants. Professor Cliff Hudis, who is the former President of the American Society of Clinical Oncology and based in New York, was the invited international guest speaker in 2014, which has become a greatly anticipated annual tutorial during the IMPACT Program. IMPACT membership is not only open to women who have had a breast cancer experience but also to anyone who wants to understand more about breast cancer clinical trials research, to enhance their ability to advocate more broadly in the community. Summary Last but certainly not least, the CAP are very honoured to be a part of the ANZBCTG research team. We are particularly proud to be members of an organisation which values and has been a leader in the inclusion of consumers in the conduct of breast cancer clinical trials. Leonie Young Chair, ANZBCTG Consumer Advisory Panel CAP Members L-R: Leslie Gilham, Cheryl Grant, Carol Whiteside, Leonie Young, Sheryl Fewster and Raewyn Calvert. Absent: Petrina Burnett and Linda Reaby. ANZBCTG Annual Report

42 Fundraising Report Ms Julie Callaghan In my role, I m very fortunate to witness daily the passion and dedication of many individuals, organisations and fundraisers who support our research program. This year, our major corporate supporter Avon made a staggering $1 million donation, their largest single donation in the 18 years of our partnership. Thanks to this donation, and the generosity of all our supporters, a record $6.43 million was raised this year. These funds are critical to ensuring more women can get the treatment they need to survive breast cancer. 20 years of progress This year marks 20 years since the Breast Cancer Institute of Australia (BCIA) was established as the fundraising department of the Australia and New Zealand Breast Cancer Trials Group (ANZBCTG). In 1994, treatment options for women diagnosed with breast cancer were limited. Clinical trials research was beginning to show solutions, but progress was constrained because resources were insufficient. The ANZBCTG was successful in obtaining grant funding from the National Health and Medical Research Council (NHMRC), and thankfully this has remained so over the years. However, government funding wasn t enough to pursue the high-quality breast cancer clinical trials research needed to make real change happen more quickly. Our Board therefore took a pro-active step into fundraising, hoping to engage like-minded and passionate individuals and corporates to help increase the number and quality of clinical trials we could conduct, accelerate progress and translate this into new treatment options for women. They were certain of the benefits additional funding could bring. Today, thanks to more than 50,000 individuals; many businesses, community groups and clubs; and our corporate supporters including Avon, the Commonwealth Bank and The Australian Women s Weekly; funds raised by BCIA play a crucial role in supporting the ANZBCTG s clinical trials research program. It s wonderful to see firsthand the outcomes of this research more women surviving their breast cancer today than ever before. Strong and fruitful partnerships I m delighted to report that our long-term partnerships with Avon, the Commonwealth Bank and The Australian Women s Weekly continue to thrive, and I m delighted to share their activities with you on the following pages. Avon has now donated $12.5 million to the breast cancer cause in Australia and New Zealand, a corporate contribution unrivalled in our region. Of this, $9.4 million has helped to fund our breast cancer clinical trials research program over the past 18 years, helping to identify and make available new breast cancer treatments and prevention strategies which are today saving lives. This year, many people chose to swim, run, walk, play golf and hold afternoon teas or special get-togethers with friends and family to raise funds for BCIA. Some of these activities are highlighted on the coming pages. I m thankful for their efforts and recognise the many special reasons that inspire and motivate our supporters. I wish to convey my sincere sympathies to the families of our supporters who have sadly passed away during the last year. I also acknowledge many of them who generously remembered the BCIA in their Will. 40 ANZBCTG Annual Report

43 My colleagues in the BCIA team have worked particularly hard this year and I thank them for their dedication and strong work ethic, and for the support they each give me. Jenny Leggett, one of the longest serving BCIA staff members with 15 years of service, retired in December. Jenny worked tirelessly to build relationships with our supporters and sponsors, in particular through her work in the Bequest Program, the annual Mother s Day Appeal, and in promotion of our Australian Women s Health Diary. Her skills, experience and happy disposition will be sorely missed by supporters and staff alike. Steady growth The growth in income is thanks to the generosity of many and in part a result of our work to bring 16,000 new supporters to BCIA; a record surplus for the 2015 Australian Women s Health Diary of $1.1 million; the generosity of donors who left a bequest to the BCIA in their Will; and the extraordinary donation of $1 million from Avon. I m very grateful to all of our supporters for their continued generosity and support. I look forward to the year ahead and to keeping them informed of the research they are helping to make possible, and the benefits of this research to them and their loved ones. Julie Callaghan General Manager, Breast Cancer Institute of Australia ANZBCTG Annual Report

44 Fundraising Results and Highlights Results Income BCIA income is raised from fundraising activities and returns on invested funds. In the 2014/2015 financial year, overall income increased by 19% on the previous year to $8,096,427, with income from fundraising activities increasing by 10% to $6,435,713 (see table below). BCIA has four main categories of fundraising income: Donations, Corporate Support, Special Events and Projects, and Bequests. 2014/ /2014 Donations $3,091,032 48% $3,172,887 54% Corporate Support $1,124,441 18% $ 761,234 13% Special Events and Projects $1,625,249 25% $1,618,770 28% Bequests $ 594,991 9% $ 286,283 5% TOTAL FUNDRAISING INCOME $6,435, % $5,839, % Expense To generate the increase in BCIA income, overall expenses increased to $2,828,763 with fundraising and administration expenses increasing to $1,978,637 (see table below). BCIA continually strives to keep all expenses to a minimum and this year s increase was expected, and in line with new fundraising strategies to acquire new donors, consolidate fundraising activities and increase resourcing. Investment in fundraising is essential as this sustains and increases the ANZBCTG s income in the long term, and enables our research program to grow and our researchers to continue pursuing high quality research outcomes for the benefit of all women and our community overall. 2014/ /2014 Fundraising and Administration Expense $1,978,637 $1,659,817 Operating Expense $ 850,126 $ 731,169 TOTAL EXPENDITURE $2,828,763 $2,390,986 BCIA s cost to fundraise is 33% and is calculated using fundraising income (excluding Bequests) as per the NSW Charitable Fundraising Act 1991 and the Best Practice Guidelines of the Office of Charities, NSW Office of Liquor, Gaming and Racing. Surplus All BCIA surplus funds are directed to the ANZBCTG research program to support the conduct of current research and the planning, development and implementation of new breast cancer clinical trials and related research activities. In the 2014/2015 financial year, BCIA surplus funds totalled $5,267,664 (see table below). 2014/ /2014 Income $8,096,427 $6,792,802 Expense $2,828,763 $2,390,986 SURPLUS $5,267,664 $4,401, ANZBCTG Annual Report

45 Highlights Our supporters throughout Australia continued to give generously this year through Individual Giving, responding to our letters, newsletters and s. In 2014, new communications via phone and mail helped to attract new members to our Regular Giving Program. We are thankful for their commitment to providing regular, monthly gifts. We sincerely thank more than 1,000 donors who have made a donation every year for more than 10 years. Their loyalty and commitment has helped to progress research which has in turn saved many lives. We strive to acknowledge and thank our donors for their generous contributions by keeping them informed of how their gifts are benefitting women with breast cancer and those at risk. Donors receive our latest clinical trials research news through our mail communications, in particular our bi-annual newsletter, as well as regular social media and communications. Our donors often respond by sharing their stories and motivations with us and we are thrilled to have received many beautiful messages again this year. These trials are too important not to support. Women everywhere need as much medical advancement in the prevention and treatment of breast cancer as possible. Peter I have a strong family history of breast cancer; research supported by the BCIA may one day help me or my family members fight this insidious disease. Laura A world without breast cancer would be a more beautiful one. Karen I am a survivor! Glad to support any research which gets to the bottom of this disease. Janise My donation is for all women everywhere. I want it to be possible for every person to survive breast cancer. Marilyn Our Bequest Program provides information and support to donors who wish to leave a gift in their Will. For many of our donors, leaving a bequest ensures their commitment to breast cancer research continues beyond their lifetime. We gratefully acknowledge the following individuals, many of whom were long-term supporters of the BCIA, for their bequests received during the reporting period: Estate of the late David Brandon Estate of the late Beverley Brown Estate of the late Josephina M Delves Estate of the late June Frances Fenton Estate of the late Eileen Hook Estate of the late Margaret Matthews Estate of the late Doriel Rowena Matzen Estate of the late Susan Louise O Brien Estate of the late Joan Stanford Estate of the late Elaine Dawn Sweetman ANZBCTG Annual Report

46 The 2014 Christmas Appeal was a great success with supporters encouraged to make a Christmas donation for someone special touched by breast cancer. Every supporter received a card on which they could write their loved one s name, attach a photo and share their reason for giving. We received hundreds of cards which we displayed as an encouragement to all our staff and researchers. The photos and messages on our beautiful Christmas display were an inspiration to us all. We re very thankful to all our supporters who donated and to those who sent messages too. Thanks to them, research can continue to help more women. Dr Soozy Smith, Chief Operating Officer, Australia and New Zealand Breast Cancer Trials Group The 2014 Direct Mail Campaigns brought new supporters to the BCIA. Again featuring Natalie Donnelly, a young mother diagnosed with breast cancer at age 44, many donors responded generously to the heartfelt story of her breast cancer experience. 44 ANZBCTG Annual Report

47 The annual Mother s Day Research Appeal successfully attracted many new supporters in 2014 who made a donation in lieu of a Mother s Day gift for their mum or loved one. This year, supporters could choose a beautiful, new animated e-card, a PDF e-card or a lovely traditional card to give to their mum which acknowledged their special gift. Response to the appeal was positive; with many thousands of Mother s Day cards delivered to special mums across Australia and supporters leaving many heartfelt messages on our website. This donation is the best way to tell your mum how much you love and appreciate her, as well as giving to breast cancer research in Australia. I can t think of a better present than trying to keep women alive long enough to be mothers, grandmothers and aunties. All of these women are special. Shona My mother passed away in July This is my first Mother s Day without her. Even though I can t physically give her a present, this donation sounded perfect. Jess As a family we decided to donate to breast cancer research this year instead of buying presents. My wife s mother (Nan) had breast cancer and is in remission. Matthew Noelle I don t need another pair of pink fluffy slippers for Mother s Day, but us women sure do need research to help fight this disease. Sharon This is my first Mother s Day as a mum and my mum s first Mother s Day as a survivor of breast cancer. Cassie ANZBCTG Annual Report

48 The Australian Women s Health Diary is an annual fundraising initiative that is much-loved by our supporters and receives wonderful support from our corporate partners. This year, the 2015 edition raised a record $1.1 million in profit bringing the total raised by the diary to $11.1 million. Supporters were able to purchase their diaries from the BCIA, newsagents, Commonwealth Bank branches, Woolworths, BIG W, Noni B, Avon Representatives and Avon s new online store. The Australian Women s Weekly has been a committed supporter of our diary producing all 17 editions on our behalf. A special team of people help bring our diary to life each year. Led by The Weekly s Managing Editor Ms Michelle Endacott, they all work tirelessly to produce this unique publication and we are indebted to them for their efforts. Co-host of the Nine Network Today Show, Lisa Wilkinson (pictured) helped us promote and spread the word about our diary and is a wonderful ambassador. Lisa, together with the support of the Nine Network, helped the diary reach more people and contributed to its great success again this year. Noni B sold the 2015 Australian Women s Health Diary in stores nationally for the first time this year. Sales were fantastic and in addition over $5,000 was collected in donations from Noni B customers. Feedback from our buyers helps us to improve the diary each year, some of which appears below. healthy heart Good health, Good living W at the same time. Quick Quiz Heart attack or Stroke: know the warning SignS If you or someone with you experience these warning signs, act quickly to increase the chance of survival. Call Triple Zero (000) for an ambulance. SignS of a Heart attack DizzineSS think F.A.S.T. ShortneSS FaCe: CheCk their of Breath face. has their mouth DroopeD? ColD Sweat on Skin pain, pressure, Arm: heaviness or Can they lift tightness Both arms? in any of these areas: Jaw ShoulDer(S) SpeeCh: is neck their SpeeCh CheSt SlurreD? BaCk Do they arm(s) understand you? nausea Time: is CritiCal. if you See any of these SignS, Call 000 Straightaway. What s the best heart-friendly snack? 1. Chocolate 2. Popcorn 3. Plain unsalted peanuts ith simple lifestyle tweaks, you number is the diastolic pressure: the lowest can love your life and your heart pressure your blood exerts when your heart is relaxed and resting between heartbeats. while very low blood pressure can cause dizziness, fainting and blurry vision, the more common health issue for australians is high Blood pressure, the measurement of the force blood pressure (known as hypertension). on blood vessels as blood travels around your hypertension may cause no obvious symptoms body, can affect the health of your heart. the for years, while it silently erodes cardiovascular ideal reading is around 120/80. the top number is the systolic pressure: the force blood places clots or plaques in the blood vessels breaking on blood vessel walls when your heart contracts off artery walls, putting you in the frontline for a heart attack or stroke. to reduce your risk: SiX StePS to Better BLooD PreSSUre to pump blood with each heartbeat. the bottom Answer 3. Unsalted peanuts 17 s unday health. over time, hypertension can lead to blood 16 s at urday CONTACTS National Heart Foundation of Australia: ; National Stroke Foundation: ; S M T W T F S S M T W T F S Friday Proudly supported by Avon M ay SignS of a Stroke use salt water gargles to reduce bacteria and boost gum health. j u n e 2015 May My wife has been using this diary daily during 2014, and I reckon she will cherish finding the 2015 edition under the Christmas tree this year. Wayne I ve had breast cancer twice: in 1998 and again in I m grateful for the care I received and see each day as a gift. Now I want to give something back. Patricia I absolutely love the weekly layout and enjoy having a good read through the tips. Also, it s a great gift and a good way to support breast cancer research. Neo I buy it to support a wonderful cause and I love reading the life tips and healthy facts that are printed throughout the diary. I have been buying it for years! Rebecca My mum has bought me the diary every year, but she passed away from breast cancer this year. I m going to keep the tradition up. Verity I have a beautiful daughter and daughterin-law. I buy them a diary at Christmas to remind them how special they are and to look after themselves. Lyn 46 ANZBCTG Annual Report

49 Avon generously donated $1 million to our research program this year. The Avon Million Reasons Campaign was launched to raise $1 million through the sale of Avon Breast Cancer Crusade Products (pictured below). Thanks to the generosity of Avon Representatives who receive no commission on these sales, and Avon customers, the $1 million donation was presented live on the Channel Nine Today Show by Cara, the Avon Representative who sold the most products during the Campaign. Avon is also a major sponsor of our Australian Women s Health Diary (see page 46). This year the 2015 edition was made available to Avon customers via the Avon Brochure and Avon s new website, resulting in increased sales and contributing to this edition s great success. ANZBCTG Annual Report

50 Our partnership with Commonwealth Bank is now in its 19th year over which time they have helped to raise $3.75 million for our research program. Commonwealth Bank has also been a major sponsor of every edition of our Australian Women s Health Diary (see page 46), helping to produce, sell and promote the diary nationwide. Maggie Beer, the Commonwealth Bank women s health ambassador, appeared on the Channel Nine Today Show with Lisa Wilkinson, Natalie Donnelly and Jean Hay to launch the 2015 Australian Women s Health Diary. Commonwealth Bank staff were also involved in a number of fundraising activities for BCIA this year. During October, branches around Australia were decorated in pink and staff hosted morning teas to raise $110,000 (photos below). CommBank Melbourne Mobile Banking Assistants Team CommBank Morisset branch staff CommBank Hornsby branch staff CommBank Hornsby branch CommBank Mandurah branch staff CommBank Corporate Financial Services, Northern and Western Melbourne 48 ANZBCTG Annual Report

51 We partner with online fundraising website Everyday Hero so that our supporters can create their own fundraising webpage based around a special event they choose to organise, or an existing event such as the Sydney City to Surf. They can personalise their webpage with photos, information, videos and more. It s also a portal through which their friends and family can donate safely to BCIA. Some of our Heroes share their motivations below. Laura Keogh participated in Run Melbourne, raising $300 for BCIA. My friend Bonnie and I trained for months for Run Melbourne. I d never run before, so it was a big challenge! My mum passed away from breast cancer when I was eight. Raising money to stop this happening to others seemed like a good thing to do. I ll try to raise even more next year! Hannah Bodilly participated in the Cole Classic swim and the Sun Run 2014, through which she raised a combined total of $890 for BCIA. My auntie and grandmother both had breast cancer, and have both since passed away, so it s a cause I personally identify with and feel strongly about. Having had my first mammogram this year also made it feel close to home. The Cole Classic was a lovely swim; it s the second time I ve done it. Although I was nervous, it was enjoyable and I finished in great time! Bibiana Tie participated in Run for a Reason WA, raising $1,513 for BCIA. A loved one of mine was diagnosed with breast cancer about one and a half years ago. I was completely blown away by the care and professionalism demonstrated by all the staff involved in her treatment. I was hoping to show my gratitude and give back in some way to the community. As a pathologist, it saddens me to meet young women with breast cancer to know that some of these women are my age or younger, have children to raise and yet have to face the question of their mortality. Ruth and Clare Horsfall participated in Run Melbourne, raising $834 for BCIA My sister Clare and I ran the half marathon because my aunt died of breast cancer back in the 70s. We want to see more progress made through research. ANZBCTG Annual Report

52 Now in its 19th year, our Tee Off for Breast Cancer Research event raised $155,000 for breast cancer research during Feedback from club members, local businesses and surrounding communities was very positive and is shared below. Congratulations to the following clubs whose fundraising efforts were particularly successful in 2014: Carpentaria Golf Club, Weipa QLD $16, Macquarie Links International Golf Club, Ingleburn NSW $8, Mornington Golf Club, Mornington VIC $7, The Australian Golf Club, Rosebery NSW $7, Bay Islands Golf Club, Macleay Island QLD $4, It s a privilege to support the ground-breaking research of the ANZBCTG through the BCIA. We have many in our ranks who are proud breast cancer survivors and we enjoy both the physical and emotional benefits of a day on the golf course. Rowes Bay Golf Club QLD The day was extremely enjoyable. Ladies participating on the day all dressed up in something pink it was very colourful-looking out on the greens and in the club rooms! Westward Ho Golf Club SA It was a fantastic day! Lots of ladies participated in golf and our lunch guests thoroughly enjoyed themselves. We were overwhelmed by the kindness and generosity of supporters, volunteers and all who attended. Macquarie Links International Golf Club NSW We all had a very enjoyable day the dining room was a sea of pink, with decorations made by the committee combined with lovely flower arrangements. Kingston Beach Golf Club TAS The event was really well attended, with everyone wearing pink. This year we even had a pink wig and matching golf shoes! Our golf members and their families were really supportive of the day once again. Exmouth Golf Club WA We had many visitors from surrounding golf clubs who came to support the event. The course looked immaculate and was decorated with pink bras on the flags and in the trees. Glorious sun shone all day and everyone enjoyed themselves immensely. Lakes View Country Club VIC 50 ANZBCTG Annual Report

53 Cooroy Golf Club QLD Glenmore Heritage Valley Country Club NSW Hawks Nest Golf Club NSW Yeppoon Golf Club QLD Mornington Golf Club VIC Alyangula Golf Club NT Mosman Park Golf Club WA Nowra Golf Club ANZBCTG Annual Report

54 Community Fundraising saw individuals, community groups, schools and businesses get creative in 2014 to raise funds for breast cancer research. Their events, large and small, were a great success and we sincerely thank all those involved for their efforts. Janice Atcheson, Doyalson North NSW Jill Hall Federal Member for Shortland, Belmont NSW Michelle and Toni King, Gunnedah NSW Paula McLachlan, Malvern East VIC Robyn and Wendy March, Valentine NSW Marie Nourse, Jerusalem SA Faye Purnell, Buttaba NSW Bayview Golf Club, Mona Vale NSW Cards Only Pty Ltd., Hornsby NSW The Cartridge Recycler Pty Ltd., Sydney NSW Castle Hill Women s Bowling Club, Castle Hill NSW Michelle King NSW Church of the Good Shepherd Handcraft Group, Cardiff NSW Classic Jaguar Enthusiasts Club Inc., Sunnybank QLD Commonwealth Bank Graduate Committee, Sydney NSW Commonwealth Bank Group Property Reaching Out Committee, Sydney NSW Commonwealth Bank Local Business Banking, Newcastle NSW Commonwealth Bank Parramatta, Sydney NSW Country Women s Association of NSW Nepean Group, Castle Hill NSW Curves Edgeworth, Edgeworth NSW Dungog Sunshine Club, Dungog NSW Handknitters Guild of Victoria, Laburnum VIC Happy Scrapper, Maryborough QLD High Tea on Grayson, Kotara NSW Hillsborough Oosh Pty Ltd., Hillsborough NSW Kmart Belconnen, Belconnen ACT Lions Club of Manly, Manly NSW Michael Hill Jeweller Charlestown Square, Charlestown NSW Bayview Golf Club NSW 52 ANZBCTG Annual Report

55 Murray Bridge Lutheran Village, Murray Bridge SA North Ryde Combined Probus Club Inc., Epping NSW Patrons of the Sacred Heart Housie, Newcastle NSW Shoalhaven Breast Cancer Support Group, Nowra NSW St David s Anglican Church, Moorabin VIC Swansea Works Co-Op Club Ltd, Swansea NSW Sutherland District Basketball Association, Suthlerland NSW Templestowe Retirement Village, Templestowe VIC Tranter Lawyers, Maitland NSW Wakky Taz Creations, Huonville TAS Wangi Newsagency, Wangi Wangi NSW White Hills Primary School, White Hills VIC Windale Gateshead Bowling Club, Windale NSW Commonwealth Bank, Local Business Banking Newcastle NSW Faye Purnell NSW Dungog Sunshine Club NSW Windale Gateshead Bowling Club NSW Sutherland Basketball Association NSW ANZBCTG Annual Report

56 Gifts received In Memory when a family member or friend dies are a meaningful and lasting way of commemorating their life and supporting breast cancer research. We sincerely acknowledge donations made during this reporting period in memory of: Mrs Jane Allen Mrs Hamida Aly Ms Kate Anderson Mrs Therese Aubert Mrs Marjorie Bailey Mrs Joyce Balnaves Mrs Joanne Wendy Barnes Mrs Fiona Beasley Mrs Molly Bell Mrs Ellen Bott Mrs Anne Bush Mrs Elizabeth Byrne Mr Ralph and Mrs Shirley Campbell Mrs Yim Ling Choong Ms Lillian Clark Ms Therese Clarke Mrs Katrina Colbran-King Ms Christine Cooper Ms Penelope Helen Creak Mrs Janet Davis Mr Colin Davis Mrs Violet Elizabeth Davis Mrs Kathleen Dawson Ms Carol de Groot Mrs Hariklia Douros Mrs Norma Monica Dowling Mrs Martha Dungo Mrs Sandra Edwards Mrs Danya Ellinghaus Mrs Amanda Donna Erickson Mrs Frances Evens Ms Vicki Fairbairn Ms Zahra Farag Mrs Alba Favaloro Ms Jessica Ferguson Mrs Juliana Gallas Mrs Vera Giblin Mrs Patricia Giroud Mrs Robyn Green Mrs Iris Halfacre Mrs Josephine Harris Mrs Winifred Hewett Mrs Margaret Hore Mrs Marion Huart Mrs Alice Ireland Mrs Margaret Jackson Mrs Veronica Januszke Mrs Marian Robina Johnson Ms Elizabeth Kidman Mrs Judith King Mrs Grace Kit Shou Lee Ho Mrs Angela Ludowici Mrs Alida McKay Mrs Leila McKenzie Mrs Stella McLeod Mrs Winsome McPherson Ms Judy Minahan Ms Alice Mouradian Mrs Ethel Murphy Mrs Margaret Rose Nance Ms Dee Neagle Ms Cindy Ng Mrs Iris Marion Nichols Mrs Brenda Orr Mrs Wendy Osborn Mrs Melba Jean Papas Miss Jane Peterson Mrs Heather Pezely Mrs Joyce Prisk Mrs Vilma Radosavljevic Mrs Doris Rhodes Mrs Joyce Rigden Ms Margaret Ringue Ms Judy Robb Mrs Linda Jane Russell Mrs Margaret Ryan Mrs Anusaya Sankhe Mrs Clara Santini Marcon Mrs Jan Simpson Mrs Dawn Sinfield Ms Sally Smith Mrs Susan Southwell Miss Athena Spliadis Mrs Patricia Statham Mrs Joan Steer Mrs Dianne Swierc Ms Helen Symeonakis Mrs Beryl Symonds Mrs Katy Tafti Mrs Fethiye Tanser Mr Nigel Thompson Mr Theodoros Tiliakos Mrs Ingrid Todd Mrs Ninette Trent Mrs Heather Turner Miss Veronica Tyson Mr Christopher Ward Ms Helen Webb Ms Barbara Williams Ms Lyn Williams Mrs Mary Winter LoLordo Mrs Pam Woods Mrs Frances Xerri Danya Ellinghaus passed away in August 2014, five years after her breast cancer diagnosis. She is loved and missed by family and friends, many of whom decided to donate to BCIA in celebration of her life and to ensure research into breast cancer continues. 54 ANZBCTG Annual Report

57 Many people generously encourage their friends and family to make an In Celebration donation to BCIA in lieu of special occasions, like birthdays. We acknowledge the following people who chose to support their special occasion in a truly giving way: Mrs Julia Burns Mrs Annette Clark Mrs Olwyne Clarke Mrs Kerrie Dighton Mrs Diane Dunbar Mr Clarrie Dupen Mrs Sheree Eberly Mrs Michelle Giesser Mr Ross Grainger Mrs Patricia Guppy Mrs Deborah Hill Mrs Julia Johnson Mrs Lorraine Maloney Mrs Helen Pearson Ms Ingrid Pusey Mr and Mrs David Pym Mrs Jan Rawlins Mrs Elizabeth Rotberg Mrs Lorna Swaffield Mrs Glenyf Thompson Mrs May Tilyard Mr and Mrs Brian Wallace Birthday Mother s Day 87th Birthday Birthday 60th Birthday 87th Birthday Birthday 60th Birthday 60th Birthday Mother s Day My life. Living with my secondaries for five years. Birthday Five years of freedom of breast cancer Ten years of good health 50th Birthday 50th Wedding Anniversary Birthday Birthday Birthday Christmas Birthday Christmas Robyn and David Pym celebrated their 50th wedding anniversary with family and friends in May Their sister-in-law Valerie Twigg donated to the BCIA in honour of Robyn and David s special occasion. ANZBCTG Annual Report

58 Governance Board of Directors 1 April 2014 to 31 March 2015 Professor Frances Boyle AM Professor Frances Boyle AM was elected to the ANZBCTG Board of Directors in 2001 and elected Chair of the Board in July Professor Boyle Chaired the ANZBCTG Scientific Advisory Committee for five years until November She is a Medical Oncologist and is Professor of Medical Oncology at the University of Sydney and Director of the Patricia Ritchie Centre for Cancer Care and Research at the Mater Hospital, Sydney and represents the ANZBCTG on the IBCSG Foundation Council. She has close links with health professionals across the spectrum of cancer care and with the medical teaching program of the University of Sydney. Professor Boyle was honoured in 2008 with Membership of the Order of Australia for work with professional and community organisations involved in cancer care and research. Associate Professor Jacquie Chirgwin Associate Professor Jacquie Chirgwin was elected to the ANZBCTG Board of Directors in 2003, was Chair from 2005 to July 2012 and is now Deputy Chair of the Board. She is also a member of the ANZBCTG Scientific Advisory Committee and has had a long commitment to clinical research spanning more than 20 years. Associate Professor Chirgwin is a Consultant Medical Oncologist at Box Hill and Maroondah Hospitals in Victoria and established breast cancer clinical trial departments in these hospitals and at the Breast Unit at Mercy Private Hospital in East Melbourne. She is Conjoint Associate Professor at the University of Newcastle and past Chair of both the Victorian Cooperative Oncology Group Breast Cancer Committee and previous Breast Tumour Stream lead and member of the Reference Group of the North Eastern Melbourne Integrated Cancer Service (NEMICS). She is also a member of several international cancer research bodies. Professor Stephen Ackland Professor Stephen Ackland was elected to the ANZBCTG Board of Directors in 2007, appointed in 2010 and re-elected in He is Conjoint Professor at the University of Newcastle, a Medical Oncologist and Senior Staff Specialist in the Medical Oncology Department at the Calvary Mater Newcastle and Director of the Hunter Cancer Research Alliance. He is a Graduate of the Australian Institute of Company Directors. Other professional activities include Director of the NSW Cancer Council from 2006 to 2014, Editor-in-Chief of the Asia Pacific Journal of Clinical Oncology and member of many international cancer research bodies. 56 ANZBCTG Annual Report

59 Associate Professor Ian Campbell ONZM Associate Professor Ian Campbell ONZM was elected to the ANZBCTG Board of Directors in 2001 and is a member of the ANZBCTG Scientific Advisory Committee. He is a Surgeon at Waikato Hospital in Hamilton, New Zealand. His academic appointment is with the University of Auckland, School of Medicine, Waikato Clinical School and is based on breast cancer clinical trials work with a special interest in local therapies and endocrine treatments, standards of care and outcomes for Maori women. Associate Professor Campbell is Chairman of the Waikato Breast Cancer Trust. He was Chairperson of the NZ Guidelines Group team producing the NZ Guidelines for Management of Early Breast Cancer and the NZ Breast Cancer Working Group developing NZ Standards of Care for Breast Cancer. He is a member of the Breast Surgeons of Australia and NZ Audit and Post Fellowship Training Subcommittees. * Retired from the Board in July Mr Paul Field Mr Field was appointed to the ANZBCTG Board of Directors in July He is Senior Investment Specialist at the Australian Trade Commission (Austrade), facilitating foreign direct investment into the advanced manufacturing, medical research and scientific sectors in Australia. He was previously Executive Chairman of Bio-Link, a business development company which worked with biotech companies, research institutes and universities to facilitate international licensing deals, including deals around tissue banks, cancer biomarkers and cancer drug candidates. * Resigned from the Board in February Professor John Forbes AM Professor John Forbes AM was appointed to the ANZBCTG Board of Directors in September He was previously a Board Director from 1991 to Professor Forbes is the Director of Research for the ANZBCTG; Professor of Surgical Oncology at the University of Newcastle; Director of the Department of Surgical Oncology at the Calvary Mater Newcastle; and Medical Director of the Breast Cancer Institute of Australia. He is a Member of the ANZBCTG Scientific Advisory Committee. Professor Forbes co-founded the ANZBCTG, and the International Breast Cancer Study Group (initially the Ludwig Breast Cancer Study Group), and was National Group Coordinator of the ANZBCTG from In 2012 Professor Forbes was honoured with Membership of the Order of Australia, in recognition for service to medicine in the field of breast cancer research, to the development of improved clinical practice standards and service to the community. Mr Michael Hamar Mr Hamar was appointed to the ANZBCTG Board of Directors in March Mr Hamar is a consultant in the field of risk management and banking. His expertise is in the fields of finance, risk management and corporate governance. He retired in 2009 from the National Australia Bank, where he was a member of the Group Executive Committee and Group Chief Risk Officer. Prior to that, Mr Hamar had a 35-year career in banking and finance working, including positions with the Commonwealth Bank of Australia, JP Morgan Chase and Bank of America, in Europe, the USA, Asia and Australia. He holds Masters degrees from Cambridge University and the University of Chicago. ANZBCTG Annual Report

60 Dr Richard Isaacs MNZM Dr Richard Isaacs MNZM was elected to the ANZBCTG Board of Directors in July Dr Isaacs is a Medical Oncologist and Head of Medical Oncology at Palmerston North Hospital, New Zealand. Dr Isaacs was Vice President of the Palmerston North Medical Research Foundation from and Chair of the New Zealand Breast Cancer Specialist Interest Group from He is immediate past Chair of the New Zealand Specialist Advisory Committee for the Royal Australasian College of Physicians and is the Secretary of the Breast Cancer Scientific Interest Group. In 2009, Dr Isaacs was awarded a New Zealand Order of Merit for services to oncology. Professor David Joseph Professor David Joseph was elected to the ANZBCTG Board of Directors in July He is Clinical Professor, School of Surgery at the University of Western Australia and Radiation Oncology Consultant at Sir Charles Gairdner Hospital and Genesis Cancer Care Bunbury. Professor Joseph has been involved with the ANZBCTG for over 20 years, is a member of the Scientific Advisory Committee and involved in publications with the International Breast Cancer Study Group. He is the Co-Chair of the International TARGIT Study, Australian Chair of the RADAR Trial, founder of The Western Australian Tissue Network and has ongoing research with the National Translational Cancer Research Network, University of Oxford UK. His specialty treatments include HDR and LDR Brachytherapy, Stereotactic Radiosurgery and Intra-Operative Radiotherapy and he is actively involved in research and innovative treatments for patients with various malignancies. Professor Geoffrey Lindeman Professor Geoffrey Lindeman was elected to the ANZBCTG Board of Directors in 2003 and is also a member of the ANZBCTG Scientific Advisory Committee. He is a Medical Oncologist at the Royal Melbourne Hospital, where he heads the RMH Familial Cancer Centre. Professor Lindeman is also Joint Head of the Stem Cells and Cancer Division and Breast Cancer Laboratory at the Walter & Eliza Hall Institute of Medical Research in Melbourne. He is a NHMRC Senior Principal Research Fellow and Lead Investigator for TransBCR (a NHMRC-funded Centre of Research Excellence in Translational Breast Cancer Research). Professor Lindeman is a Fellow of the Australian Academy of Health and Medical Sciences and is also a member of the Executive of kconfab (a consortium studying hereditary breast cancer) and the Victorian Cancer Biobank Consortium Committee. Professor John Simes Professor John Simes was elected to the ANZBCTG Board of Directors in 1991 and is also a member of the ANZBCTG Scientific Advisory Committee. Professor Simes is a Medical Oncologist at the Royal Prince Alfred Hospital Sydney, a Professor of Clinical Epidemiology at the University of Sydney and Director of Sydney Catalyst Translational Cancer Research Centre. He is the founding Director of the NHMRC Clinical Trials Centre (CTC) and is responsible for the CTC s research program. His research interests include clinical trials methodology, quality of life assessment and integrating trial evidence with the goal of improving clinical practice and health outcomes. He has been co-awarded an NHMRC Program Grant on Advancing the Evidence Base for Care and Policy in Priority Health Areas. * Retired from the Board in July ANZBCTG Annual Report

61 Scientific Advisory Committee (SAC) 31 March 2015 Assoc Prof Nicholas Wilcken Chair Assoc Prof Prue Francis Vice Chair Prof Bruce Mann Chair, SAC Local Therapy Subcommittee Prof Phyllis Butow Co-Chair, SAC Supportive Care Subcommittee Prof Kelly-Anne Phillips Co-Chair, SAC Supportive Care Subcommittee Assoc Prof Nicole McCarthy Chair, SAC Systemic Therapy Subcommittee Prof Frances Boyle AM Assoc Prof Ian Campbell ONZM Assoc Prof Jacquie Chirgwin Assoc Prof Boon Chua Prof Alan Coates AM Prof Joanna Dewar Prof John Forbes AM Assoc Prof Glenn Francis Prof Val Gebski Ms Cheryl Grant Prof Michael Green Prof David Joseph Dr Belinda Kiely Dr Marion Kuper-Hommel Dr Chee Lee Prof Geoffrey Lindeman Mrs Dianne Lindsay Assoc Prof Sherene Loi Dr Janine Lombard Dr Nick Murray Dr David Porter Assoc Prof Clare Scott Prof R John Simes Assoc Prof Raymond Snyder Assoc Prof Andrew Spillane Ms Leonie Young Medical Oncologist Medical Oncologist Surgical Oncologist Psycho-Oncologist Medical Oncologist Medical Oncologist Medical Oncologist Surgical Oncologist Medical Oncologist Radiation Oncologist Medical Oncologist Medical Oncologist Surgical Oncologist Pathologist ANZBCTG Group Statistician ANZBCTG Consumer Advisory Panel Medical Oncologist Radiation Oncologist Medical Oncologist Medical Oncologist Medical Oncologist Medical Oncologist / Clinician-Scientist Head of Trials Management, ANZBCTG Medical Oncologist Medical Oncologist Medical Oncologist Medical Oncologist Medical Oncologist / Clinician-Scientist Medical Oncologist / Statistician Medical Oncologist Surgical Oncologist ANZBCTG Consumer Advisory Panel Honorary Members: Prof John Collins Dr Ron Kay Surgical Oncologist Medical Oncologist ANZBCTG Annual Report

62 Independent Data Safety and Monitoring Committee Prof Martin Tattersall Chair Prof Matthew Law Prof Michael Quinn Assoc Prof Sandra Turner Prof John Zalcberg Consumer Advisory Panel Members 31 March 2015 Leonie Young Chair Consumer Coordinator, IMPACT Program Petrina Burnett Raewyn Calvert Sheryl Fewster Leslie Gilham Cheryl Grant Adjunct Prof Linda Reaby AM Carol Whiteside QLD WA NZ WA VIC NSW ACT NSW Staff Member Listing 1 April 2014 to 31 March 2015 Heath Badger Corinna Beckmore Lauren Boyes Helen Braggett Julie Callaghan Tamar Carpenter Vanessa Cheung Angie Chung Anna Cummins Haley Deacon Annette Dempsey Cheryl Dodds Donna Douglass Breanna Edman Melissa Eveleigh Team Leader Project Officer Protocol Development Team Leader Trial Coordinator (Maternity Relief) BCIA General Manager BCIA Fundraising Data Manager Trial Coordinator Project Officer Regulatory Affairs (Maternity Relief) BCIA Appeal Coordinator Trial Coordinator Senior Trials Coordinator BCIA Donor Relations Officer Administration Assistant BCIA Gift Processing Officer Trial Coordinator 60 ANZBCTG Annual Report

63 Anna Fitzgerald Akiko Fong Nicole Francis Sharyn Frank Helen Garner Juliette Gritten Leigh Hainsworth Maria Hartman Jacqui Henderson Tamica Humby Elizabeth Hutchings Connie Irvine Angela Johns Amy Jongerden Ingrid Laycock Jenny Leggett Dianne Lindsay Rose Lucas Mai Ly Lauren Macnab Kelly Martin Carlie Mavin Belinda Mitchell Rebecca Moder Sandy Morris Anthony Morrison Jane Murphy Vicki Murray Rachael O Donnell Lisa Paksec Leonie Phillott David Pringle Flonda Probert Stuart Reeves Hollie Ritchie Alison Sheppard Soozy Smith Kristy Taubman Victoria Tayler Rochelle Thornton Christine Wasik Julianne Webb Nicholas Zdenkowski Communications Manager Senior Trials Coordinator Administration Assistant Information Support Officer Personal Assistant to Professor John Forbes Administration Assistant BCIA Bequest Officer Trial Coordinator BCIA Appeal Communications Manager Trial Coordinator Project Officer Concept Development Trial Coordinator Project Officer Ethics and Regulatory Affairs Trial Coordinator (Maternity Relief) Senior Trials Coordinator BCIA Public Relations Manager Head of Trials Management Project Officer Regulatory Affairs Trial Coordinator Senior Trials Coordinator BCIA Donor Development Manager Senior Trials Coordinator Senior Trials Coordinator / Team Leader (Acting) Quality Assurance Officer BCIA Appeal Coordinator (Acting) Trial Coordinator BCIA Gift Processing Officer BCIA Gift Processing Officer Accounts Administrator Ethics and Regulatory Affairs Manager Human Resources Advisor Financial Controller Trial Coordinator Trial Coordinator Project Officer Regulatory Affairs Executive Assistant to the Chief Operating Officer Chief Operating Officer Trial Coordinator Special Projects Officer Team Leader Accounts Administrator Trial Coordinator Clinical Fellow ANZBCTG Annual Report

64 Contributors and Supporters International Collaborators Breast International Group (BIG) Breast European Adjuvant Studies Team (BrEAST) Cancer Trials Support Unit (CTSU) Clinical Trial Service Unit (CTSU) Cancer Research UK (CRUK) Eastern Cooperative Oncology Group (ECOG) German Breast Group (GBG) International Breast Cancer Study Group (IBCSG) National Institute of Canada, Clinical Trials Group (NCIC-CTG) National Surgical Adjuvant Breast and Bowel Project (NSABP) / NRG Oncology SouthWest Oncology Group (SWOG) Translational Research in Oncology (TRIO) Belgium Belgium USA UK UK USA Germany Switzerland and USA Canada USA USA France and Canada Participating Institutions Australian Capital Territory Metropolitan The Canberra Hospital Garran Canberra New South Wales Metropolitan Bankstown-Lidcombe Hospital The Breast & Endocrine Centre Calvary Mater Newcastle The Chris O Brien Lifehouse Concord Repatriation General Hospital Liverpool Hospital Macarthur Cancer Therapy Centre Macquarie Cancer Clinical Trials Mater Hospital Nepean Cancer Care Centre Newcastle Private Hospital Prince of Wales Hospital Royal North Shore Hospital Royal Prince Alfred Hospital St George Hospital Bankstown Sydney Gateshead Newcastle Waratah Newcastle Camperdown Sydney Concord Sydney Liverpool Sydney Campbelltown Sydney Macquarie Park - Sydney North Sydney Sydney Kingswood Sydney New Lambton Heights Newcastle Randwick Sydney St Leonards Sydney Camperdown Sydney Kogarah Sydney 62 ANZBCTG Annual Report

65 St Vincent s Hospital San Clinical Trials Unit Westmead Hospital Regional Armidale Hospital Coffs Harbour Health Campus Gosford Hospital Lismore Base Hospital Manning Rural Referral Hospital Orange Health Service Port Macquarie Base Hospital Riverina Cancer Care Centre Southern Highlands Cancer Centre Tamworth Rural Referral Hospital The Tweed Hospital Wollongong Hospital Darlinghurst Sydney Wahroonga Sydney Westmead - Sydney Armidale Coffs Harbour Gosford Lismore Taree Orange Port Macquarie Wagga Wagga Bowral Tamworth Tweed Heads Wollongong Queensland Metropolitan Icon Cancer Care Wesley Mater Adult Hospital Mater Cancer Care Centre Princess Alexandra Hospital Royal Brisbane and Women s Hospital Regional Cairns Hospital Nambour Hospital St Andrew s Toowoomba Hospital Townsville Hospital Auchenflower Brisbane South Brisbane Brisbane South Brisbane Brisbane Woolloongabba Brisbane Herston Brisbane Cairns Nambour Toowoomba Townsville South Australia Metropolitan Flinders Medical Centre Lyell McEwin Hospital The Queen Elizabeth Hospital Royal Adelaide Hospital Bedford Park Adelaide Elizabeth Vale Adelaide Woodville South Adelaide Adelaide Tasmania Metropolitan Royal Hobart Hospital Hobart ANZBCTG Annual Report

66 Regional North West Regional Hospital Launceston General Hospital Mersey Community Hospital Burnie Launceston Latrobe Victoria Metropolitan The Alfred Hospital Austin Hospital Box Hill Hospital Cabrini Hospital Epworth Richmond Hospital Footscray Hospital Maroondah Hospital Monash Breast Clinic Monash Cancer Centre Monash Medical Centre The Northern Hospital Peter MacCallum Cancer Centre The Royal Melbourne Hospital The Royal Women s Hospital St Vincent s Hospital Sunshine Hospital Victorian Breast & Oncology Care Prahran Melbourne Heidelberg Melbourne Box Hill Melbourne Malvern Melbourne Richmond Melbourne Footscray Melbourne Maroondah Melbourne Clayton Melbourne East Bentleigh Melbourne East Bentleigh - Melbourne Epping Melbourne East Melbourne Melbourne Parkville Melbourne Parkville Melbourne Fitzroy Melbourne St Albans Melbourne East Melbourne Melbourne Regional Ballarat Health Services Ballarat Oncology and Haematology Services The Bendigo Hospital Border Medical Oncology Frankston Hospital Frankston Private Goulburn Valley Health University Hospital Geelong Ballarat Wendouree Bendigo Wodonga Frankston Frankston Shepparton Geelong Western Australia Metropolitan Fiona Stanley Hospital Mount Hospital Royal Perth Hospital St John of God Hospital Sir Charles Gairdner Hospital Murdoch Perth Perth Perth Subiaco Perth Nedlands Perth 64 ANZBCTG Annual Report

67 Regional St John of God Hospital Bunbury New Zealand Metropolitan Auckland City Hospital North Shore Hospital Wellington Hospital Auckland Auckland Wellington South Wellington Regional Christchurch Hospital Dunedin Hospital Palmerston North Hospital St George s Hospital Waikato Hospital Christchurch Dunedin Palmerston North Christchurch Hamilton Funders and Supporters Breast Cancer Research Foundation, USA Cancer Australia National Breast Cancer Foundation National Health and Medical Research Council University of Newcastle Sponsors Corporate Sponsors The Cartridge Recycler Noni B ANZBCTG Annual Report

68 Financial Report Mr David Pringle The ANZBCTG is a not-for-profit, collaborative, national and international breast cancer clinical trials research group. It is an independent public company limited by guarantee with academic affiliations. The ANZBCTG is governed by a Board of Directors and the terms of its Constitution. The Board of Directors has a Finance and Audit Subcommittee (FAC) to assist with its financial oversight responsibilities. This Board Subcommittee has a Terms of Reference and meets four times per year. Financial management of the ANZBCTG has two main facets: management of ANZBCTG Ltd finances and resources; management of competitive and other grant funds administered by other Institutions. The financial statements included in this report are for the ANZBCTG Ltd legal entity and therefore do not include transactions relevant to the management of grants administered by other institutions. Each year, the ANZBCTG undergoes independent financial audit to ensure its compliance with all applicable company, taxation, charitable and financial legislation and regulation. Financial Management of the ANZBCTG The Chief Operating Officer supported by the Financial Controller undertakes the day to day financial management according to the delegations vested by the Board, and ensures the ANZBCTG adheres to applicable Australian corporate, taxation and charity legislation. Sources of ANZBCTG income include: fundraising income (donations, special events, corporate support) and bequests 54%; investment income on funds generated from fundraising 14%; clinical trials research program (pharmaceutical partnerships, international collaborative group partnerships) 25%; competitive grants awarded to the ANZBCTG 4%; other income (Annual Scientific Meeting registration fees and sponsorship, and sundry items) 3%. Areas of ANZBCTG expenditure include: clinical trials research program (clinical trials development, activation, coordination and quality assurance activities, funding for participating institutions, randomisation and statistical analyses, staff member salaries, Annual Scientific Meeting and other meetings) 52%; fundraising and fundraising administration 20%; other recurrent monthly infrastructure costs, including administration staff salaries, IT, rent, insurances and other core business expenses 28%. 66 ANZBCTG Annual Report

69 Financial Management of Competitive Grant Funds Administered by other Institutions The ANZBCTG applies for and secures competitive grants. Competitive grant funding mechanisms include streams for both research and infrastructure funding, and can be sourced from many organisations including but not limited to: National Health and Medical Research Council (NHMRC) (government); Cancer Institute NSW (government); Cancer Councils (government/private); National Breast Cancer Foundation (private); Other Trusts and Foundations. Most competitive grant funds are administered by a recognised 'administering institution' and it is the responsibility of the administering institution to financially and legally account for the grants it administers. The University of Newcastle is the ANZBCTG's usual administering institution and competitive grant funding administered by this or other institutions is not shown in the financial statements of ANZBCTG Ltd. Financial Results for the year ended March 2015 For the year ended March 2015 ANZBCTG Ltd reported net income of $2.173 million, which is a $0.768 million improvement on the result for the prior year. Gross income increased by $2.042 million from the prior year with increased income from the clinical trials program (due to increased activity) and increases in both fundraising and investment income. Expenditure increased by $1.274 million, mainly due to increased activity on clinical trials. During the year the net assets of ANZBCTG Ltd increased from $ million to $ million. The ANZBCTG is therefore in a strong position to continue its research program and to fund its commitment to existing trials, many of which will require funding well into the future. David Pringle Financial Controller ANZBCTG Annual Report

70 Financial Statements The statements contained in this Financial Report are a summary of the independently audited accounts for the financial year ended 31 March Full audited financial statements are available by contacting the ANZBCTG. Any ANZBCTG surplus is committed to the long term follow-up of ongoing research projects and in supporting current and future ANZBCTG research projects. All ANZBCTG payroll liabilities are annually expensed to the external suppliers which manage the ANZBCTG s payroll. Income and Expenditure Statement 2015 ($000) 2014 ($000) Variation ($000) INCOME Clinical trials research program 3,000 2, Fundraising activities 6,436 5, Earnings from investments 1, Other Income TOTAL INCOME 11,934 9,892 2,042 EXPENDITURE Clinical trials research program 5,097 4,352 (745) Fundraising and administration 1,979 1,660 (319) Administration support for the clinical trials program 2,685 2,475 (210) TOTAL EXPENDITURE 9,761 8,487 (1,274) NET INCOME 2,173 1, Analysis of Income and Expenditure Income Expenditure Clinical Trials Research Program Fundraising Activities Earnings from Investments Other Income Clinical Trials Research Program Fundraising and Administration Administration Support for the Clinical Trials Program 68 ANZBCTG Annual Report

71 Statement of Financial Position 2015 ($000) 2014 ($000) Variation ($000) CURRENT ASSETS Cash and Short Term Investments 13,799 16,565 (2,766) Trade and Other Receivables 3,052 2, Other Current Assets Total current assets 17,263 19,029 (1,766) NON-CURRENT ASSETS Property, plant and equipment (298) Long term investments 7,624 3,463 4,161 Other non-current assets (14) Total non-current assets 8,004 4,155 3,849 TOTAL ASSETS 25,266 23,183 2,083 TOTAL CURRENT LIABILITIES 2,318 2,408 (90) NET ASSETS/ EQUITY 22,949 20,776 2,173 Note that each number in the above table is rounded to the nearest $000. ANZBCTG Annual Report

72 Publications In the reporting period from 1 April 2014 to 31 March 2015, the ANZBCTG contributed to 33 peer reviewed publications. Bellet M, Gray KP, Francis PA, Lang I, Ciruelos E, Lluch A, Climent MA, Catalan G, Costa RF, Catalan R, Rajasekaran A, Morales J, Vazquez J, Fleming GF, Price KN, Regan MM, SOFT-EST Investigators, SOLTI and International Breast Cancer Study Group. Estrogen levels in premenopausal (prem) patients (pts) with hormone-receptor positive (HR+) early breast cancer (BC) receiving adjuvant triptorelin (Trip) plus exemestane (E) or tamoxifen (T) in the SOFT trial: SOFT-EST substudy. J Clin Oncol. 2014; 32:5s (suppl; abstr 585). Bernhard J, Luo W, Ribi K, Colleoni M, Burstein HJ, Tondini C, Pinotti G, Spazzapan S, Ruhstaller T, Puglisi F, Pavesi L, Parmar V, Regan MM, Pagani O, Fleming GF, Francis PA, Coates AS, Gelber RD, Goldhirsch A, Walley B, SOFT and TEXT Investigators and International Breast Cancer Study Group. Patient-reported endocrine symptoms, sexual functioning, and quality of life (QoL) in the IBCSG TEXT and SOFT trials: Adjuvant treatment with exemestane (E) plus ovarian function suppression (OFS) versus tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC). J Clin Oncol. 2014; 32:5s (suppl; abstr 557). Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF. 16 year long-term follow-up of the IBIS-I breast cancer prevention trial. SABCS. 2014; Abstract S3-07. Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF, on behalf of the IBIS-I Investigators. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015; 16: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim Jr HA, Kim S-B, Kuemmel S, Huang C-S, Vuylsteke P, Hsieh R-K, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014; 15(10): de Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, Untch M, Smith IE, Gianni L, Baselga J, Jackisch C, Cameron DA, Bell R, Leyland-Jones B, Dowsett M, Gelber RD, Piccart-Gebhart MJ, Suter TM. Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin adjuvant trial (BIG 1-01). J Clin Oncol. 2014; 32(20): de Boer R, Beith J, Chirgwin J, Chua S, Colosimo M, Francis P, Green M, Pittman K, White M, Wilcken N, Zdenkowksi N, Bell R. Systemic treatment of HER2-positive metastatic breast cancer: Clinical conundrums and future perspectives. Asia-Pac J Clin Oncol. 2014; 10(suppl. 4): Dueck AC, Hillman DW, Kottschade LA, Halyard MY, Sloan JA, Flickinger LM, Wolff AC, Harris L, Gralow J, Pritchard KI, Ellard S, Le-Lindqwister N, Boyle FM, De Azambuja E, McCaskill-Stevens WJ, Zujewski JA, Piccart-Gebhart MJ, Perez EA. Quality of life (QOL) among patients (pts) with HER2+ breast cancer (bc) treated with adjuvant lapatinib and/or trastuzumab in the ALTTO study (BIG 2-06, Alliance N063D). J Clin Oncol. 2014; 32:5s (suppl; abstr 647). Forbes JF, Dowsett M, Bradley R, Ingle JN, Aihara T, Bliss JM, Boccardo FM, Coates AS, Coombes RC, Cuzick JM, Dubsky PC, Gnant M, Kaufmann M, Kilburn LS, Perrone F, Rea D, Thurlimann BJK, Van De Velde CJH, Davies C, Gray RG, on behalf of EBCTCG s AIOG. Patient-level meta-analysis of randomized trials of aromatase inhibitors (AI) versus tamoxifen (Tam). J Clin Oncol. 2014; 32:5s (suppl; abstr 529). 70 ANZBCTG Annual Report

73 Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD, for the SOFT Investigators and the International Breast Cancer Study Group. Adjuvant Ovarian Suppression in Premenopausal Breast Cancer. New Engl J Med. 2015; 372(5): Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos EM, Bellet M, Bonnefoi H, Climent MA, Pavesi L, Burstein HJ, Martino S, Davidson NE, Geyer Jr CE, Walley BA, Coleman RE, Kerbrat P, Rabaglio-Poretti M, Coates AS, Goldhirsch A, Gelber RD. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Analysis of the SOFT trial. SABCS. 2014; Abstract S3-08. Giobbie-Hurder A, Thürlimann B, Ejlertsen B, Neven P, Coleman RE, Smith I, Wardley AM, Láng I, Colleoni M, Debled M, Forbes JF, Price KN, Regan MM, Rabaglio M, Goldhirsch A, Coates AS, Gelber RD. IBCSG BIG 1-98 study: The long-term follow-up experience. SABCS. 2014; Poster P Johansson H, Gray KP, Pagani O, Regan MM, Viale G, Aristarco V, Macis D, Puccio A, Roux S, Maibach R, Colleoni M, Rabaglio-Poretti M, Coates AS, Gelber RD, Goldhirsch A, Kammler R, Bonanni B, Walley BA. CYP19A1 and ESR1 polymorphisms and selected early-onset side effects during combined endocrine therapy in the IBCSG TEXT trial for premenopausal women with hormone receptor-positive (HR+) early breast cancer. SABCS. 2014; Poster P Liu MC, Rack B, Dueck AC, Hillman DW, Campion MB, Reinholz M, Halling KC, Sotiriou C, Rothé F, Maetens M, Rouas G, Janni W, Wolff AC, Harris LN, Gralow JR, Pritchard KI, Ellard S, Le-Lindqwister NA, Boyle F, De Azambuja E, Piccart-Gebhart MJ, Ignatiadis M, Perez EA. Circulating tumor cell (CTC) enumeration and HER2 assessment as predictors of breast cancer outcomes in the ALTTO (BIG 2-06, Alliance N063D) Trial. SABCS. 2014; Poster P Lombard JM, Zdenkowski N, Wells K, Grant N, Reaby L, Forbes JF, Chirgwin J. Aromatase inhibitor induced musculoskeletal syndrome (AIMSS) in Australian women with early breast cancer: An Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) survey of members of the Breast Cancer Network Australia (BCNA). SABCS. 2014; Poster P Mackey JR, Ramos-Vazquez M, Lipatov O, McCarthy N, Kraznozhon D, Semiglazov V, Manikhas A, Gelmon KA, Konecny GE, Webster M, Hegg R, Verma S, Gorbunova V, Gerges DA, Thireau F, Fung H, Simms L, Buyse M, Ibrahim A, Martin M. Primary results of ROSE/TRIO-12, a randomized placebo controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. J Clin Oncol. 2015; 33(2): Moore HCF, Unger JM, Phillips K-A, Boyle FM, Hitre E, Porter DJ, Francis PA, Minasian LM, Gelber RD, Goldstein LJ, Gomez HL, Vallejos C, Partridge AH, Dakhil SR, Martino S, Barlow WE, Fabian CJ, Meyskens FL, Hortobagyi GN, Albain KS. Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). J Clin Oncol. 2014; 32:5s (suppl; abstr LBA505). Moore HCF, Unger JM, Phillips K-A, Boyle F, Hitre E, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partidge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens Jr FL, Gelber RD, Hortobagyi GN, Albain KS, for the POEMS/S0230 Investigators. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015; 372: Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA, for the TEXT and SOFT Investigators and the International Breast Cancer Study Group. Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer. New Engl J Med. 2014; 371(2): ANZBCTG Annual Report

74 Pagani O, Regan MM, Walley B, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE, Rabaglio-Poretti M, Coates AS, Gelber RD, Goldhirsch A, Francis PA, SOFT and TEXT Investigators and International Breast Cancer Study Group. Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials. J Clin Oncol. 2014; 32:5s (suppl; abstr LBA1). Phillips KA, Feng Y, Ribi K, Bernhard J, Puglisi F, Bellet M, Crivellari D, Karlsson P, Budman DR, Zaman K, Abdi EA, Domcheck SM, Regan MM, Coates AS, Gelber RD, Maruff P, Boyle F, Forbes JF, Fleming GF, Francis PA. Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT). SABCS. 2014; Poster P Phillips K-A, Steel EJ, Collins I, Emery J, Pirotta M, Mann GB, Butow P, Hopper JL, Trainer A, Moreton J, Antoniou AC, Cuzick J, Keogh L. Transitioning to routine breast cancer risk assessment and management in primary care: what can we learn from cardiovascular disease? Aust J Prim Health. 2015; 24 February:e-pub. Piccart-Gebhart MJ, Holmes AP, Baselga J, De Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Santillana S, Pritchard KI, Wolff AC, Jackisch C, Lang I, Untch M, Smith IE, Boyle F, Xu B, Gomez HL, Gelber RD, Perez EA. First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-her2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC). J Clin Oncol. 2014; 32:5s (suppl; abstr LBA4). Ribi K, Luo W, Bernhard J, Francis PA, Bellet M, Burstein HJ, Pavesi L, Parmar V, Tondini C, Visini M, Torres R, Karlsson P, Spazzapan S, Avella A, Ruhstaller T, Puglisi F, Regan MM, Coates AS, Gelber RD, Fleming GF. Patient-reported endocrine symptoms, sexual functioning, and quality of life (QoL) in the IBCSG SOFT trial: Adjuvant treatment with tamoxifen (T) alone versus T plus ovarian function suppression (OFS) in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC). SABCS. 2014; Poster S3-09. Saura C, de Azambuja E, Dubsky P, Oliveira M, Saini KS, Fesl C, Lin RS, Fredrickson J, Parmar H, Hsu JY, Piccart M, Gnant M, Baselga J. LORELEI: A phase II randomized, double-blind study of neoadjuvant letrozole plus taselisib (GDC-0032) versus letrozole plus placebo in postmenopausal women with ER-positive/HER2-negative, early stage breast cancer. SABCS. 2014; Poster OT Sestak I, Cuzick J, Dowsett M, Lopez-Knowles E, Filipits M, Dubsky P, Cowens JW, Ferree S, Schaper C, Fesl C, Gnant M. Prediction of late distant recurrence after 5 years of endocrine treatment: A combined analysis of patients from the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol. 2015; 33(8): Sestak I, Singh S, Cuzick J, Blake GM, Patel R, Gossiel F, Coleman R, Dowsett M, Forbes JF, Howell A, Eastell R. Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2014; 15: Sieuwerts AM, Willis S, Burns MB, Look MP, Meijer-Van Gelder ME, Schlicker A, Heideman MR, Jacobs H, Wessels L, Leyland-Jones B, Gray KP, Foekens JA, Harris RS, Martens JWM. Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers. Horm Canc. 2014; 5(6): Stearns V, Chapman J-AW, Ma CX, Ellis MJ, Ingle JN, Pritchard KI, Budd GT, Rabaglio M, Sledge GW, Le Maitre A, Kundapur J, Liedke PER, Shepherd LE, Goss PE. Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. J Clin Oncol. 2015; 33(3): Wilcken N, Zdenkowski N, White M, Snyder R, Pittman K, Mainwaring P, Green M, Francis P, de Boer R, Colosimo M, Chua S, Chirgwin J, Beith J, Bell R. Systemic treatment of HER2-positive metastatic breast cancer: A systematic review. Asia-Pac J Clin Oncol. 2014; 10(suppl. 4): ANZBCTG Annual Report

75 Zdenkowski N, Butow P, Fewster S, Beckmore C, Wells K, Forbes J, Boyle F. ANZBCTG : DOMINO Exploring decision making about neoadjuvant chemotherapy for operable breast cancer. MOGA ASM. 2014; Poster. Zdenkowski N, Butow P, Mann GB, Fewster S, Beckmore C, Isaacs R, Boyle FM, on behalf of the ANZBCTG. Neoadjuvant systemic therapy for breast cancer: A survey of Australian and New Zealand (ANZ) specialists. St Gallen IBCC. 2015; Poster P199. Zdenkowski N, Butow PN, Fewster S, Beckmore C, Wells K, Forbes JF, Boyle FM. Exploring decision making about neoadjuvant chemotherapy for early breast cancer. J Clin Oncol. 2014; 32(suppl; abstr e20578). ANZBCTG Annual Report

76 Glossary of Terms ACCRUAL TARGET (RECRUITMENT TARGET): The number of participants planned to be enrolled in the trial. ADJUVANT THERAPY: Additional treatment used to improve the effects of surgical treatment. In cancer, adjuvant therapy may include chemotherapy, hormonal or radiation therapy after surgery, which is aimed at killing any remaining cancer cells. ADJUVANT! ONLINE: An internet-based computer program to assist health professionals and patients to discuss the risks and benefits of additional therapy options after breast cancer surgery. ADVANCED BREAST CANCER: Cancer that has spread from the original site in the breast (metastasised) to other organs or tissues in the body. Also known as secondary breast cancer or metastatic breast cancer. ANGIOGENIC: Blood vessel formation, which usually accompanies the growth of malignant tissue. ANTIANGIOGENIC MOLECULE: An orally delivered small-molecule formulation with antiangiogenic and anticancer activity. AROMATASE INHIBITORS (AI) (examples: anastrozole, exemestane and letrozole): A class of drugs used in the treatment of breast cancer in postmenopausal women. Some cancers require oestrogen to grow. Aromatase is an enzyme that synthesises oestrogen. Aromatase inhibitors block the synthesis of oestrogen. This lowers the oestrogen level, and slows the growth of cancers. AXILLA: The underarm or armpit. AXILLARY DISSECTION: Surgery to remove lymph nodes from the armpit. The procedure can be performed either at the same time as breast surgery or as a separate operation. AXILLARY LYMPH NODES: Lymph nodes in and near the armpit. BIOMARKERS: Measurable biological characteristics associated with the presence or absence of disease. Biomarkers can help with the diagnosis, prognosis and treatment of diseases such as cancer. BIOPSY: The removal of a small sample of tissue or cells from the body to help diagnose a disease. BReast CAncer 1 and 2 genes (BRCA1 and BRCA2): genes that make proteins that help to repair DNA. BREAST CONSERVING SURGERY: Surgery to remove part of the breast. Also called a lumpectomy or a wide local excision. CHEMOTHERAPY (examples: cyclophosphamide, doxorubicin, docetaxel and capecitabine): The use of medications (drugs) that are toxic to cancer cells. These drugs kill the cells, or prevent or slow their growth. The standardised combination of such drugs in the treatment of cancer is referred to as a treatment regimen. CYCLIN-DEPENDENT KINASE 4/6 INHIBITOR (CDK) (example: palbociclib): A drug that blocks the CDK4 and CDK6 proteins which stops certain processes that cause cancer cells to grow and multiply. CLINICAL TRIAL: Research conducted with the participant s consent which usually involves a comparison of two or more treatments or diagnostic methods. Clinical trials are conducted to gain a better understanding of the underlying disease process and/or methods to treat or prevent it. The clinical trial process includes Phase I, II, and III trials. DIMERISATION INHIBITOR: An antibody that prevents a compound or unit being produced by the combination of two like molecules. DOUBLE-BLIND TRIAL: A clinical trial in which neither the participating individual nor the study staff knows which participants are receiving the experimental drug and which are receiving a placebo or another therapy. DUCTAL CARCINOMA IN SITU (DCIS): Abnormal cells in the breast ducts, which over time could develop into invasive breast cancer. EARLY (Primary) BREAST CANCER: Breast cancer that has not spread beyond the breast or the axillary lymph nodes. This includes ductal carcinoma in situ and stage I, IIA, IIB, and IIIA breast cancers. 74 ANZBCTG Annual Report

77 ELIGIBILITY CRITERIA: Participant eligibility criteria for clinical trials can range from general (age, type of cancer) to specific (prior treatment, tumour characteristics, blood cell counts, organ function). Eligibility criteria may also vary with the stage of the disease. ENDOCRINE-RESPONSIVE: Another name for hormone-responsive, or hormone receptor-positive breast cancer. Refer also to hormone (endocrine) treatment. ENDPOINT: Endpoints are used to measure the effect of a treatment being used in a clinical trial. Primary endpoints measure outcomes that will answer the primary (or most important) question being asked in a clinical trial, such as whether a new treatment is better at preventing disease-related death than the standard therapy. Secondary endpoints measure other relevant trial outcomes. GONADOTROPIN-RELEASING HORMONE(GnRH) ANALOGUE/AGONIST: A medication such as goserelin or triptorelin that temporarily stops the ovaries from producing oestrogen. This type of medication is only effective for premenopausal women. GOOD CLINICAL PRACTICE (GCP): An international standard for the design, conduct, performance, recording and reporting of clinical trials; that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected. GRADE (TUMOUR GRADE): The degree of similarity of the cancer cells to normal cells. Grade is assessed by a pathologist. Grade 1 carcinoma is well differentiated and is associated with a better prognosis. Grade 2 carcinoma is moderately differentiated and is associated with an intermediate prognosis. Grade 3 carcinoma is poorly differentiated and is generally associated with a worse prognosis. HER2-POSITIVE (HER2-amplified): HER2 stands for Human Epidermal Growth Factor Receptor 2. In HER2-positive breast cancer, the cancer cells have an abnormally high number of HER2 genes per cell. When this happens, too much HER2 protein appears on the surface of these cancer cells. This is called HER2 protein over expression or amplified. Too much HER2 protein is thought to cause cancer cells to grow and divide more quickly. HER SIGNALLING PATHWAYS: One of the many complex processes associated with cell communication and action. The role of specific molecules in a cell which, via a cascade effect, inhibit or allow particular cell functions. Drugs being developed to inhibit these pathways might lead to new ways to block cancer cell growth and kill cancer cells. HORMONE (ENDOCRINE) TREATMENT: Hormone (endocrine) treatment is used to treat breast cancers that are hormone receptor-positive, also known as hormone-responsive or endocrine-responsive. These cancers have receptors for the hormones oestrogen and/or progesterone; they are called ER and/or PR-positive cancers. There are several different types of hormone treatments. Some are taken as tablets (tamoxifen or aromatase inhibitors) and some are treatments to turn off or remove the ovaries (injections, surgery and sometimes radiotherapy). HORMONE RECEPTORS: Proteins in a cell which bind to specific hormones. This stimulates the cell to act in a particular way. HORMONE REPLACEMENT THERAPY (HRT): Drug therapy that supplies the body with hormones that it is no longer able to produce; usually to relieve menopausal symptoms. HORMONE-RESPONSIVE: Also known as hormone receptor-positive or endocrine-responsive breast cancer. HUMAN RESEARCH ETHICS COMMITTEE (HREC): The Human Research Ethics Committee s function is to review proposed research in order to ensure that the subject s rights are protected and that risk of harm is minimised. HYPOTHESIS: Provides a suggested solution based on evidence. IMMUNOHISTOCHEMISTRY (or IHC): Used to identify tissue components (e.g. abnormal cells in a cancerous tumour, different parts of biological tissue) by using a marker such as a fluorescent dye or an enzyme. The marker is attached to a type of protein (antigen) that finds another type of protein (antibody) and reacts to colour the target cells. INDEPENDENT DATA SAFETY AND MONITORING COMMITTEE (IDSMC): An independent group of experts or adequately qualified individuals who monitor participant safety and treatment effectiveness data while a clinical trial is ongoing. INFORMED CONSENT: Informed consent is a process whereby a person gives consent based on a clear understanding of the facts, any implications and possible future consequences. In the case of a clinical trial, these facts, implications and consequences are conveyed in the Participant Information Sheet and any associated materials. IPSILATERAL: On or affecting the same side of the body. ANZBCTG Annual Report

78 ISOFORM: Any of two or more functionally similar proteins that may have a similar but not identical amino acid sequence, for example, there are two known isoforms of the oestrogen receptor, alpha (α) and beta (β). LOCALLY ADVANCED BREAST CANCER: Breast cancer that has one or more of the following features: may be large (typically bigger than 5 cm); may have spread to several lymph nodes in the armpit (axilla) or other areas near the breast; and may have spread to other tissues around the breast such as the skin, muscle or ribs. LUMPECTOMY: Also called Breast Conserving Surgery. LYMPHOEDEMA: Swelling caused by a build-up of lymph fluid, as a result of lymph nodes being removed or not working properly. MADAROSIS: Loss of the eyelashes or of the hair of the eyebrows. MAGNETIC RESONANCE IMAGING (MRI): A medical imaging device using a strong magnetic field and radio frequency to produce detailed images of internal body parts and structures. MRI is especially useful for imaging soft tissue like the brain, heart, muscles and tumours. MAMMOGRAM: An x-ray of the breast. MASTECTOMY: The surgical removal of the whole breast. METASTATIC BREAST CANCER: Cancer that has spread from the original site in the breast to other organs or tissues in the body. Also known as secondary breast cancer or advanced breast cancer. MICROMETASTASES: Small cancer cells that have spread (metastases) beyond the primary tumour and can only be detected by microscopic evaluation. MONOCLONAL ANTIBODIES (examples: trastuzumab and bevacizumab): A treatment designed to specifically target a cell within the body, particularly cancer cells. Different cancer types can be targeted with different monoclonal antibodies. MORBIDITY: The relative incidence of a particular disease within a defined population. NEOADJUVANT: Treatment given prior to surgery or further treatment for cancer. NODAL STATUS: Whether a breast cancer has spread (node-positive) or has not spread (node-negative) to lymph nodes in the armpit (axillary nodes). The number and site of positive axillary nodes can help predict the risk of cancer recurrence. OESTROGEN: The main female sex hormone produced mostly by the ovaries. OESTROGEN RECEPTOR (ER): A protein that may be present on certain cells to which oestrogen molecules can attach. The term ER-positive refers to tumour cells that contain the oestrogen-receptor protein. These cells are generally sensitive to hormone therapy. OESTROGEN RECEPTOR ALPHA (ERα): One of two specific Oestrogen Receptor (ER) proteins. In standard clinical practice ERα is the primary ER protein assessed when determining if a tumour is ER-positive. OESTROGEN RECEPTOR BETA (ERβ): One of two specific Oestrogen Receptor (ER) proteins. ERβ is the less common variation of the ER protein and is not routinely assessed in standard clinical practice. ONCOLOGIST: A doctor who specialises in treating cancer. ONCOLOGY: A branch of medicine that deals with cancer. OOPHORECTOMY: The surgical removal of an ovary or ovaries. OPEN-LABEL TRIAL: A clinical trial in which doctors and participants know which drug or treatment is being administered. OSTEOPOROSIS: A disease characterised by low bone mass and deterioration of bone architecture, which increases the susceptibility to fractures. OVERALL SURVIVAL (OS): The time from trial randomisation until death from any cause. Overall survival is regarded as the gold standard measure of benefit in clinical trials and requires a large number of patients and long term follow-up. 76 ANZBCTG Annual Report

79 PARTICIPANT INFORMATION SHEET: A document designed to provide participants with relevant information and facts relating to the proposed clinical trial in order for the participant to make an informed decision regarding their participation in the trial. PARTICIPATING INSTITUTION: Any public or private hospital or facility where ANZBCTG clinical trials are conducted. PHASE II CLINICAL TRIAL: The second stage of the evaluation of a new drug in humans; these trials evaluate drug safety and preliminary efficacy (effectiveness) in a large number of participants (up to several hundred). PHASE III CLINICAL TRIAL: The most rigorous and extensive type of scientific clinical investigation of a new treatment. These trials are designed to determine the effectiveness of a treatment, often by comparing it to an existing standard therapy or a placebo, in a large number of participants (typically hundreds or thousands). A phase III trial is generally required before a drug would be approved by regulatory authorities for general use. PI3K (Phosphatidylinositol 3 -kinase): a protein produced by the body that can change the cell-to-cell communications which affect cell growth and survival. PLACEBO: An inert tablet (such as a sugar pill), liquid or powder that has no active ingredient. In clinical trials, experimental treatments are often compared with a placebo to assess the treatment s effectiveness. PREDICTIVE FACTOR: A finding which assists a clinician to assess whether an individual s cancer will respond either positively or negatively to a particular treatment. For example, the presence of oestrogen receptors predicts for response to hormone treatment. This term is often confused with prognostic factor. PREVENTION TRIAL: A trial aiming to find better ways to prevent breast cancer in healthy women. PRINCIPAL INVESTIGATOR (PI): The person responsible for overseeing all aspects of a clinical trial at an ANZBCTG participating institution; recruiting participants; obtaining informed consent; and collecting data. PROGESTERONE RECEPTOR (PR): A protein that may be present on certain cells to which progesterone molecules can attach. The term PR-positive refers to tumour cells that contain the progesterone-receptor protein. These cells are generally sensitive to hormone therapy. PROGNOSTIC FACTORS: The combination of a number of aspects of a person s general condition and disease diagnosis. General factors can include, but are not limited to, age, gender, lifestyle and medical history. Specific disease related factors can include disease diagnosis, stage, tumour size and location and treatment options. The combination of these factors can result in either a favourable or poor prognosis. PROGRESSION-FREE SURVIVAL (PFS): The time from trial randomisation until cancer progression or death from any cause. PFS is considered a surrogate of overall survival, with the advantage that it can be measured in smaller clinical trials with shorter follow-up. Therefore it can be used to bring new therapies into clinical practice in a shorter timeframe. PROTOCOL: A written, detailed action plan for a clinical trial. The protocol provides the background, specifies the objectives, and describes the design and organisation of the trial. QUALITY OF LIFE: An individual s overall appraisal of their situation and subjective sense of well-being. RADIOTHERAPY: The use of radiation, usually x-rays or gamma rays, to kill cancer cells or damage them so they cannot grow and multiply. RANDOMISATION: A method of preventing bias in research by randomly assigning clinical trial participants to treatment groups. Randomisation ensures each treatment group has a similar range and number of participants, such that any differences between treatment groups at the end of the trial can be attributed to the trial treatments. RANDOMISED TRIAL: A study in which participants are randomly assigned to one of two or more treatment arms of a clinical trial. RECURRENCE: The return of breast cancer after a period of remission. During a recurrence, breast cancer cells which have evaded treatment may reappear at the original site or in another part of the body. RECURRENCE SCORE: Obtained by the Oncotype DX Assay, is a numerical value between representing the likelihood of recurrence to distant parts of the body at 10 years post diagnosis. ANZBCTG Annual Report

80 SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERM) (examples: tamoxifen and raloxifen): A class of medication that acts on the oestrogen receptors of cells by blocking the effects of naturally produced oestrogen within the body. This form of treatment has been shown to be effective in hormone-sensitive breast cancers. SENTINEL NODE: The hypothetical first lymph node or group of nodes reached by metastasising cancer cells from a primary tumour. SENTINEL NODE BIOPSY: Sampling of the sentinel lymph node into which the primary tumour is draining first to determine if a full lymph node exploration is needed. SIDE EFFECTS: Unwanted effects of a drug or treatment (e.g. nausea, headache, hair loss, etc). Side effects may be short or long term, ranging from minor inconveniences to serious adverse events. STANDARD TREATMENT (THERAPY): The current best treatment known for a particular disease or condition. STUDY CHAIR: An adequately qualified clinician assigned by the ANZBCTG to provide clinical advice and guidance for the development and ongoing conduct of a clinical trial. STUDY COORDINATOR: A member of the research team at an ANZBCTG participating institution who takes responsibility for non-clinical aspects associated with the conduct of a clinical trial. SUPRA-CLAVICULAR FOSSA: An indentation (fossa) immediately above the clavicle, or collar bone. SYSTEMIC THERAPY: The use of chemotherapy, hormone therapy and/or targeted therapy or a combination of these to target the entire body to destroy any cancer cells that may have spread to distant body parts but are below the level of clinical detection. TOXICITY: Harmful side effects from an agent being tested. TREATMENT TRIALS: Treatment trials are designed to test the safety and effectiveness of new drugs, biological agents, techniques, or other interventions in people who have been diagnosed with cancer. These trials evaluate the new treatment against standard treatment, if there is one. TRIPLE-NEGATIVE METASTATIC BREAST CANCER (TNBC): Triple-negative is the term given to tumours which do not possess Oestrogen Receptor (ER) and Progesterone Receptor (PgR) proteins, and which do not over express the HER2 protein. TYROSINE KINASE INHIBITOR (example: lapatinib): A drug that interferes with cell communication and growth and which may prevent tumour growth. 78 ANZBCTG Annual Report

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84 Research for a world without breast cancer. The Australia and New Zealand Breast Cancer Trials Group is supported by its fundraising department the Breast Cancer Institute of Australia.