Expert: Dr Olivia Pagani, Oncology Institute of Southern Switzerland, Lugano, Switzerland Discussant: Dr Fedro Alessandro Peccatori, European Institute of Oncology, Milan, Italy e-session 381 BCY3 - Highlights of the 3rd ESO-ESMO Breast Cancer in Young Women International Conference To share your e-eso experience use: #e_eso 2
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DEFINITION OF YOUNG < 40 years because these women have specific issues related to FERTILITY PRESERVATION, PREGNANCY, AND LACTATION that deserve a different approach and management from slightly older preand peri-menopausal women 3 Breast. 2016;26:87-99.
4.7% BC accounts for more than 40% of all cancers in this age group Courtesy Dr Azim, BCY3 4
SEER 2000 2011 Polednak AP J Cancer Epidemiol. 2015 5
MAIN MESSAGES All patients, both in the early and advanced setting, should be discussed within a multidisciplinary breast unit team (breast nurses crucial as navigators ). This can be best achieved in specialized breast clinics Personalized psychosocial support, counselling on genetic predisposition, sexuality and fertility should be highly recommended as part of the individual treatment planning. Long-term treatment side effects are particularly relevant in young women with their potential long-term survival. There are a lot of unknowns & insufficient data RESEARCH PRIORITIES 6 Breast. 2016;26:87-99.
General recommendations In young women, innovative and structured communication and supportive tools (e.g. online programs, web-based interventions) should be developed and scientifically validated and disseminated in different languages. This would help young patients to overcome barriers to accessing support, such as child and family care, work timetables and distance issues. (LoE: Expert opinion) 7
General recommendations Biology and prognosis Systematic research into age-specific tumor characteristics is needed. In particular the prognostic and predictive impact of multitarget gene expression and mutational status to identify specific genomic aberrations that could open the door for tailored therapeutic interventions. (LoE: Expert opinion) 8
N=243,012 (Year 1988 2003) < 40 (n=15,548) > 40 (n=227,464) P-value T > 2cm 61.4% 48.2 <0.0001 Node-positive 45.4% 33.6% <0.0001 ER-negative 28% 14.2% <0.0001 PgR-negative 30.1% 20.4% <0.0001 Grade 3 42.6% 25.9% <0.0001 Courtesy Dr Azim, BCY3 9 Gnerlich JL et al; J Am Coll Surg 2009
Chi-square: p<0.0001 Basal Luminal-A Luminal-B HER2 Courtesy Dr Azim, BCY3 10
R e l a p s e - f r e e s u r v i v a l ( % ) R e l a p s e - f r e e s u r v i v a l ( % ) R e l a p s e - f r e e s u r v i v a l ( % ) R e l a p s e - f r e e s u r v i v a l ( % ) R e l a p s e - f r e e s u r v i v a l ( % ) 1 0 0 8 0 6 0 4 0 2 0 0 p < 0. 0 0 0 1 Prognosis of BC in young women Particularly poorer outcome in ER+ tumors W h o l e p o p u l a t i o n ( n = 2 9 0 9 ) 0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0 T i m e ( d a y s ) 4 0 ( n = 3 4 1 ) 4 1-5 2 ( n = 9 7 3 ) 5 3-6 4 ( n = 7 3 3 ) 6 5 ( n = 8 6 2 ) 1 0 0 8 0 6 0 4 0 2 0 0 1 0 0 8 0 6 0 4 0 2 0 0 p = 0. 0 7 L u m i n a l A ( n = 9 7 5 ) 0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0 p = 0. 0 7 T i m e ( d a y s ) L u m i n a l A ( n = 9 7 5 ) 0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0 T i m e ( d a y s ) 1 0 0 8 0 6 0 4 0 2 0 0 p = 0. 0 3 L u m i n a l B ( n = 8 7 9 ) 0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0 T i m e ( d a y s ) B a s a l - l i k e ( n = 6 1 5 ) 0 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0 Courtesy Dr Azim, BCY3 11 Azim HA Jr et al; Clin Cancer Res 2012 1 0 0 8 0 6 0 4 0 2 0 0 p = 0. 6 9 T i m e ( d a y s )
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Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival. 13
Genetic counseling and testing The multidisciplinary management of mutation carriers and highrisk individuals should be ideally provided in dedicated high-risk clinics. (LoE: Expert opinion) 14
Genetic counseling and testing Genes to be tested for depend on personal and family history. Although BRCA1/2 are the most frequently mutated genes, other additional moderate- to high-penetrance genes may be considered if deemed appropriate by the geneticist/genetic counsellor. (LoE: Expert opinion) Development of quality-controlled genetic counseling services is strongly encouraged. 15
Screening, diagnosis & imaging for staging and FU No specific data with tomosynthesis are available in young women. Its use and indications are the same as in other age groups. (LoE: Expert opinion) Risk-adapted early detection and surveillance should be researched in young women (LoE: Expert opinion) 16
SURGERY 17
Vila J, Gandini S, Gentilini O. The Breast 2015 18
Early breast cancer loco-regional treatment Indications and schedules of hypo-fractionation are in principle the same as in other age groups, despite no long-term toxicity data available. (LoE: 1 B) Indications and extension of nodal irradiation are the same as in other age groups. (LoE: 1 B) PBI has not been sufficiently studied in young patients and should not be performed in this age group. (LoE: Expert opinion) Indications of adjuvant RT are independent of BRCA status. Data are stronger for benefits of post-mastectomy (PM) RT for young women. 19
Early breast cancer loco-regional treatment The optimal loco-regional treatment after neoadjuvant chemotherapy is still controversial: decisions should be made independent of age. Mutation status should be part of the individual decision-making algorithm. Sufficient time to discuss the different options and adequate psychological support should be offered given the potential long term sequela and implications.. (LoE: Expert opinion) 20
Neoadjuvant systemic treatment In patients with TNBC or BRCA-associated tumors the incorporation of platinum agents increases pcr rates and may be considered when neoadjuvant chemotherapy is indicated. Data on the impact of incremental increases in pcr on long term outcome are not conclusive. (LoE: 2A) Potential additional impact on fertility and increased toxicity that may compromise standard duration and dosing of standard systemic treatment need to be clearly communicated to patients. 21
Neo/Adjuvant systemic treatment For patients with TNBC not achieving a pcr after standard neoadjuvant regimens, the routine addition of adjuvant chemotherapy (such as capecitabine or metronomic CM) is not recommended, however, may be considered in highly selected patients on an individual basis, as in other age groups. (LoE: Expert opinion) 22
Adjuvant systemic treatment A number of factors including patient and tumor characteristics and gene expression tests, where available, may be considered when deciding whether to administer adjuvant chemotherapy in young women with ER+ breast cancer. Further research on this subject is needed. Commercially available gene expression tests have not been widely studied in young women. Less data are available to establish their role in predicting the additional benefit of chemotherapy over ET alone in ER+ breast cancer in this age group. (LoE: Expert opinion) 23
MammaPrint MINDACT Chemo No chemo High clinical risk / low genomic risk 5 year freedom from distant mets = 95% 6 5 5 3-5 4 4 1-5 2 4 0 All MammaPrint provides similar prognostic info even in young 0 2 4 6 8 1 0 H a z a rd ra tio (9 5 % C I) 24 Cardoso F et al; NEJM 2016
TAILORx RS < 10 Sparano et al, NEJM, 2015 25
Adjuvant systemic treatment In highly selected patients with small, node-negative, HER-2+ breast cancer, the administration of 12 weeks of weekly paclitaxel and trastuzumab without anthracyclines can be discussed, as in other age groups. (LoE: Expert opinion) All patients Disease-Free Survival (Probability) 0.0 0.2 0.4 0.6 0.8 1.0 0 12 24 36 48 60 Time (Months) Number at risk 406 390 382 307 126 27 Tolaney et al, NEJM 2015;372:134-41. 26
Adjuvant systemic treatment In view of the long potential life expectancy, particular attention should be paid to possible long-term toxicities of adjuvant treatments (e.g. secondary cancers, cardiovascular toxicity, irreversible ovarian failure, weight gain, cognitive function, bone health). Clinics dedicated to the assessment and management of early and late treatment side effects, adherence to treatment and follow-up guidelines should be developed. 27
Advanced breast cancer The BCY3 panel endorses the ESO-ESMO ABC 3 guidelines for the management of ABC in pre-menopausal women. MAIN MESSAGE! Also in the metastatic setting, age alone is not a reason to prescribe more aggressive therapy. 28
Advanced breast cancer In women who harbor a BRCA mutation and/or have triple negative subtype use of platinum agents should be considered in the advanced disease setting. (LoE: 2B) Many trials in ER+ ABC have not included pre-menopausal women. Despite this, we recommend that young women with ER+ ABC have adequate ovarian suppression or ablation and then be treated in the same way as post-menopausal women with endocrine agents and targeted therapies such as an aromatase inhibitor or fulvestrant plus a CDK 4/6 inhibitor or exemestane with everolimus. Future trials exploring new endocrine/endocrine-biological strategies should be designed to allow for enrollment of both preand post-menopausal women. 29
Supportive and follow-up care Psychosocial oncology care Young women with breast cancer are at higher risk for psychosocial distress. Patients distress and psychosocial needs should be regularly assessed. Psychosocial care should be available and integrated in routine cancer treatments and follow-up. Partners and family members should be involved early on and couple-based psychosocial interventions should be promptly proposed if needed. (LoE: 3B) 30
Supportive and follow-up care All young women should be informed about approved fertility preservation options and referred for special counseling/consultation if interested in fertility preservation prior to commencement of any therapy. 31
PREGNANCY AFTER BREAST CANCER 32
Retrospective, multicenter cohort study (7 Institutions) 1,207 eligible patients Primary endpoint: DFS ER+ pts. Secondary endpoints: DFS in ER- pts., OS Subgroup analysis: J Clin Oncol. 2013 Jan 1;31(1):73-9 DFS according to time of pregnancy DFS according to breastfeeding 33
OS in whole population HR 0.72 (95%CI 0.54-0.97) Azim HA Jr et al JCO 2013;31(1):73-9. 34 Median follow up from conception 4.7 years
Overall survival in ER+ patients Date of conception Median follow-up from date of conception: 4.7 years (IQR: 3.1 6.9) Azim HA Jr et al JCO 2013;31(1):73-9. 35
What about breast feeding? 36
No Breastfeeding Pregnant, n=39 Controls, n=90 Breastfeeding Pregnant, n=25 Controls, n=56 0 1 2 3 HR (95% CI) Better DFS in Pregnant Better DFS in Controls Gelber S, JCO 19:1671, 2001 Azim HA Jr 37et al JCO 2013;31(1):73-9.
Screening/eligibility: 1 + CT Patients with ER+ early breast cancer 18 and 42 years at enrollment Completing 18-30 months of ET (SERMs alone, GnRH analogue + SERM or AIs) 1 Pregnancy desire Stop ET 2 2 No more than 1 month prior enroll. E N R O L L M E N T 0 3 months wash out ET stopped 1 month prior to enrollment Translational research 3 POSITIVE schema Up to 2 years break to allow conception, delivery ± breast feeding ET resumption to complete 5 (-10) yrs 24 mos Follow-up Ovarian function evaluation Uterine evaluation Circulating tumor DNA (ctdna) Psycho-oncological companion study Genomic evaluation of primary breast tumor Accrual: 38 70 pts overall 10 yrs
Motherhood after breast cancer through adoption Cancer. 2015;121:2993-3000 Courtesy Dr Peccatori, BCY3 39
Motherhood after breast cancer through adoption Cost might be relevant (3.000-75.000$) Cancer history could place restrictions on the adoption Agencies may ban cancer survivors from adopting newborns Cancer survivors may feel uncertain about their future Positive feelings from birth mothers 40
After cancer Everyone deserves a sex life including: The young adult The older patient Patients in relationships Patients without a partner LGBTQ patients Patients with advanced or metastatic disease The oncologist Courtesy Dr Dizon, BCY3 41 Photo credit: mrshustle.files.wordpress.com
Supportive and follow-up care Young patients should be strongly encouraged to adopt the following healthy life style changes: - maintain BMI 25 - perform regular aerobic exercise - not to smoke - to limit daily alcohol intake 42
SUMMARY STATEMENT ON BEHALF OF THE YOUNG WOMEN ADVOCATES Medha Sutliff, USA; YSC Tanja Spanic, SI; ED 43 Slovenia
Our voice 1. Quality of life for young BC patients 2. Survivorship long term side effects and economic impact on young BC patients 3. Fertility Preservation 4. Clinical trials for young BC patients 5. Research and legislative advocacy training opportunities for young BC patients 44