Breast cancer. Prof Arlene Chan Medical Oncologist Director Breast Clinical Trials Unit, Mount Hospital Vice-Chair Breast Cancer Research Centre - WA

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Brett Morton
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1 Breast cancer rof Arlene Chan Medical Oncologist Director Breast Clinical Trials Unit, Mount Hospital Vice-Chair Breast Cancer Research Centre - WA

3 Breast cancer

4 Incidence of Breast Cancer by Stage at Diagnosis (Europe 2005) Stage Number % of Total Stage I 70, % Stage II 85, % Stage III 17, % Stage IV 11, % Total 184, %

5 Cumulative survival Metastatic breast cancer: improved survival over time Months

6 How do we approach breast cancer management to improve outcome?

7 Research Genetics Diagnosis SYSTEMIC treatment (Drugs) LOCO-REGIONAL treatment (Surgery & Radiation therapy Improve outcome in patients with breast cancer

8 Estrogen exposure: Risk factors» hysiological, Exogenous Growth factors» Obesity, Alcohol re-cancerous breast conditions Chest irradiation huge doses Breast cancer-susceptible genes*

9 Diagnosis EBC (stage 1-3)» Earlier diagnosis translates into higher chance of cure» Once diagnosed, plan best surgery ± reconstruction ± radiation therapy» Discuss relapse risk» Systemic treatment MBC (stage 4) Earlier diagnosis does not translate into higher rate of response or survival Tissue diagnosis*** for type of BrC Assess extent of BrC Assess fitness Give best therapy based on evidence-based research

10 Systemic therapy: rinciples

11 Breast cancer is a heterogeneous* disease -> Different sub-types which behave differently: Different growth rates Responds to treatment differently (drugs / radiation therapy) Although may prefer certain sites in body, this does not have major effect on management * Dissimilar; possessing different or opposing characteristics in the same individual

12 Basal-like HER-2 Normal Luminal B Luminal A Sørlie et al. roc Natl Acad Sci USA. 2001;98:

13 Metastatic disease is generally considered incurable but Very treatable Many options available need to use in correct order Choice depends on: Sub-type of breast cancer Where and how much metastatic cancer Underlying fitness of patient Any previous treatment given

14 Growth factor Estrogen lasma membran e ER EGFR / Her2 Her3/Her2 Cell survival IGFR I3-K Akt p90 RSK EGFR / HER2 SOS RAS RAF MAK MEK Cytoplas m ER ER p160 CB Basal transcription machinery Cell growth Nucleus ERE ER target gene transcription Adapted from Johnston S. Clin Cancer Res. 2005;11:889S-899S.

15 Types of systemic therapy Endocrine therapy» Tamoxifen» Aromatase inhibitors: Letrozole, Anastrozole, Exemestane» Ovary suppression Chemotherapy Biologic therapy

16 Biological drug Supportive tissues cells Endocrine drug Chemotherapy drug VEGF TGF ER EGFR HER2 VEGF-R GF-R Cell membrane Signaling cascade Gene transcription Nuclear membrane Inside cell Cell growth and proliferation Inhibition of apoptosis Increased cell mobility Tumor growth Resistance to chemotherapy Metastasis

17 Breast cancer Research

18 rinciples Concept Desig n Tumour behavior Understand tumour biology Understand patient needs? Scientific design: atients in study must be the same Must show it s not a chance finding rimary aim to be achieved Source funding Timely recruitment Many centres required Execution Regulatory aspects Collect all data (years) Constant check of data Analyse data ublish

19 U.S. FDA approval in MBC Cyclophosphamide 1959 Methotrexate 1971 Doxorubicin 1974 Docetaxel 1996 aclitaxel 1994 Capecitabine 1998 Trastuzumab 2000 Gemcitabine 2004 Nab paclitaxel 2005 Lapatinib 2007 Bevacizumab

20 Conclusions Breast cancer has many facets» Risks Detection Differing behaviour» Local & Systemic treatment options» Early vs Metastatic disease» Short & Long term consequences of treatment» Addressing non-medical needs Multidisciplinary approach Best outcome requires application of scientifically-proven treatments Education of: atients Community/Gov G Allied health Specialists

What has been learned in 2014 for metastatic breast cancer?

What has been learned in 2014 for metastatic breast cancer? rof Arlene Chan Medical Oncologist Director Breast Clinical Trials Unit, Mount Hospital Vice-Chair Breast Cancer Research Centre - WA Answer:»