Systemic Management of Breast Cancer

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1 Systemic Management of Breast Cancer Why Who When What How long Etc. Vernon Harvey Rotorua, June 2014

2 Systemic Management of Breast Cancer Metastatic Disease Adjuvant Therapy Aims of therapy Quality of life Prolongation of life Identify best therapy Aim of therapy Enhance cure

3 Systemic Management of Breast Cancer Metastatic Disease Adjuvant Therapy Options Endocrine therapy Chemotherapy Biological therapy Options Endocrine therapy Chemotherapy Biological therapy

4 Systemic Management of Breast Cancer Metastatic Disease Adjuvant Therapy For whom Symptomatic Fit enough Want therapy For whom Dependant on baseline risk Patient wishes

5 Metastatic Breast Cancer Options But which. Endocrine therapy ER/PR positive Chemotherapy Biological therapy HER2 positive Hormones Chemo Chemo Hormones Both together Chemo + Biological (if HER2 +)

6

7 Metastatic Breast Cancer General Principles Hormone therapy Chemotherapy * Symptom Control (with Herceptin if HER2+) * Some prefer chemotherapy first for life threatening disease

8 Metastatic Breast Cancer Endocrine Therapy (ER and/or PR positive) Tamoxifen Ovarian Ablation (premenopausal) Aromatase inhibitors (postmenopausal) Progestogens Faslodex Chemotherapy Anthracyclines Taxanes Capecitabine Vinorelbine Biological Therapy (HER2 positive) Trastuzumab (Herceptin) Lapatinib

9 Metastatic Breast Cancer Endocrine Therapy (ER and/or PR + only) Single drug Sequential therapy Continue to progression Chemotherapy (ER/PR- or failed hormones) Single or combination Sequential therapy Duration limited by toxicity Achievements Control in 30-60% Control in 30-60% Average duration 9-12 mths Average duration 9-12 mths Wide variation Wide variation

10 Adjuvant Therapy of Breast Cancer Rationale Disease that appears localised may have spread beyond the breast. Therapy that is only palliative in MBC may eliminate microscopic disease

11 Adjuvant Therapy of Breast Cancer Options Endocrine therapy ER/PR positive Chemotherapy Biological therapy HER2 positive But which. Hormones (for most ER+) Chemotherapy (depends on risk) Biological (with Chemo) (if HER2 +) BUT to whom..

12 Adjuvant Therapy of Breast Cancer The Concept of Risk

13 Adjuvant Therapy of Breast Cancer Assessing the Risk

14 Adjuvant Therapy of Breast Cancer Assessing the Risk

15 Adjuvant Therapy of Breast Cancer Assessing the Risk

16 Adjuvant Therapy of Breast Cancer Assessing the Risk

17 Adjuvant Therapy of Breast Cancer Assessing the Risk Oncotype DX

18 Adjuvant Therapy of Breast Cancer Effective Therapy - Proportional to Risk

19 Adjuvant Therapy of Breast Cancer Endocrine Therapy ER and/or PR + Most patients (except very low risk) Options Tamoxifen Ovarian Suppression Premenopausal only Aromatase Inhibitors postmenopausal only preferable for N+ disease Duration Tamoxifen 5-10 years AI 5 years

20 ATAC Trial tamoxifen vs 10 years

21 Adjuvant Therapy of Breast Cancer Endocrine Side-effects Tamoxifen Emotional change Thrombo-embolism (DVT) Endometrial Cancer Ovarian Suppression Menopausal symptoms Aromatase Inhibitors Arthralgia Increased bone loss

22 ATLAS Trial 5 vs 10 years of tamoxifen

23 Adjuvant Therapy of Breast Cancer Chemotherapy For those at higher risk (? Benefit > 5%) Duration 4 8 cycles Side-Effects Neutropenic fever Nausea Hair Loss Infertility / Menopausal symptoms Chemo brain

24 Adjuvant Therapy of Breast Cancer Trastuzumab (Herceptin) HER2 positive only (15% of breast cancer) With chemotherapy Duration 12 months (optimal unknown) Side-effects Myocardial dysfunction Probably temporary Long term consequences unknown

25 Adjuvant Therapy of Breast Cancer HERA Trial DFS over time Median follow-up (% follow-up time after selective crossover) 2005 (0%) 1 yr MFU 0.54 DFS benefit No. of DFS events 1 year trastuzumab vs observation 127 vs 220 P< (4.3%) 2 yrs MFU vs 321 P< (33.8%) 4 yrs MFU vs 458 P< (48.5%) 8 yrs MFU vs 570 P< Favours 1 year trastuzumab Favours observation HR (95% CI) Extended from Gianni et al. Lancet Oncol

26 Adjuvant Therapy of Breast Cancer Trastuzumab (Herceptin) HERA 4 years D DFS

27 Adjuvant Therapy of Breast Cancer The Future Better predictors of risk mtor inhibitors to reverse endocrine resistance Chemotherapy at about maximum Newer anti-her2 medications New genetic targets identified

28 Adjuvant Therapy of Breast Cancer The Future

29 We are moving forward but never as quickly as we want or patients need Thank you

30 Back-up slides

31 Adjuvant Therapy of Breast Cancer Assessing the Risk

32

33 MBC Response to Endocrine therapy Before After 3 months

34 Adjuvant Therapy of Breast Cancer The Effectiveness of Therapy

35 HRG (NRG1) Adjuvant Therapy of Breast Cancer HER2 Family of Genes Ligand binding domain Transmembrane Tyrosine kinase domain neu Erb-b2 HER2 Erb-b3 HER3 Erb-b4 HER4

36 Systemic Management of Breast Cancer Metastatic Disease Adjuvant Therapy When When symptoms require Patient need When 2-6 weeks post surgery Before surgery for some large tumours

37

38 Adjuvant Therapy of Breast Cancer Assessing the Risk

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