What's New in Metastatic Research and Clinical Trials: ER Positive and Triple-Negative Breast Cancer
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Slides and audio for this presentation are available on YouTube: http://youtu.be/NJ0HTrH-uog Nancy Lin, MD, of the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, talks about the differences between various types of breast cancer, and the new therapies that are being developed to treat the disease. This presentation was originally given at the Metastatic Breast Cancer Forum held at Dana-Farber on Oct. 5, 2013. The program was sponsored by EMBRACE (Ending Metastatic Breast Cancer for Everyone).
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What's New in Metastatic Research and Clinical Trials: ER Positive and Triple-Negative Breast Cancer
- 1. What’s New in Metastatic Research and Clinical Trials: ER Positive and Triple-Negative Breast Cancer Nancy Lin, MD Susan F. Smith Center for Women’s Cancers Dana-Farber Cancer Institute October 5, 2013
- 2. Overview • • • • Breast cancer subtypes Recent drug approvals Exciting research directions Clinical trials
- 3. Breast Cancer Subtypes • There are three main subtypes of breast cancer • Within these, there are other ways to further sub-divide breast cancers • Oncologists use the breast cancer subtype to guide the kinds of treatments to recommend • Clinical trials often will focus on specific subtypes
- 4. Breast Cancer Subtypes Breast cancer subtype Estrogen receptor and/or HER2 Progesterone receptor ER-positive (Hormone receptor positive) + - HER2-positive + or - Triple-negative +++ - -
- 5. Breast Cancer Subtypes Breast Cancer Subtypes ER-positive HER2-positive Triple-negative TALK to your doctor if you are not sure what type of breast cancer you have
- 6. Hormone receptor positive Triple-negative HER2-Positive Herceptin + perjeta + chemotherapy Hormonal therapy Chemotherapy TDM1 Hormonal therapy Chemotherapy Chemotherapy Herceptin + chemotherapy Chemotherapy Chemotherapy Lapatinib +Herceptin Herceptin + chemotherapy *Note, these are just examples. Each patient is different and treatment is tailored accordingly.
- 7. New Drug Approvals: Afinitor • 3.2 Aromasin months* •7.8 months* Aromasin + Afinitor *Median time from study entry until worsening of cancer Approved by the FDA in 2012 for patients with metastatic, hormone-receptor positive, HER2-negative breast cancer
- 8. New Drug Approvals: Eribulin •Metastatic breast cancer •At least 2 prior chemotherapies Approved by the FDA in 2011 Halichondria okadai
- 9. Key Research Questions 1. How many subtypes of breast cancer are there, and by understanding this, can we find new targets and new treatments? Can we better “tailor” treatments? 2. Which molecular features are important and which are just “along for the ride? 3. What causes resistance to hormonal therapy? To chemotherapy? Can it be prevented or overcome?
- 10. There are more than 3 breast cancer subtypes… Curtis et al, Nature 2012
- 11. What About Looking at Specific Gene Changes? Obtain tumor biopsy material Extract DNA/RNA from tumor to profile for somatic alterations Slide courtesy of Dr. Nikhil Wagle
- 12. OncoMap Mutations 900 800 Number of Samples 700 600 500 400 300 200 100 0 GI GYN THORAX BREAST GU H/N HEME DERM SARCOMA UNKNOWN ABL1 AKT1 AKT2 APC BRAF CDKN2A CTNNB1 EGFR ERBB2 FGFR2 FGFR3 FLT3 GNA11 GNAQ GNAS HRAS IDH1 IDH2 JAK2 JAK3 KIT KRAS MAP2K1 MET MLH1 MYC NPM1 NRAS PDGFRA PIK3CA PIK3R1 PTEN RB1 RET STK11 TP53 VHL NEURO WT Slide courtesy of Dr. Nikhil Wagle As of 5/13/2013
- 13. Polyak and Filho, Cancer Cell, 2012
- 14. Which clues will turn out to lead to new treatments??…
- 15. CLINICAL TRIAL HIGHLIGHTS: ER+ or Triple-Negative breast cancer
- 16. Testing the addition of an HSP90 inhibitor to hormonal therapy
- 17. Tumor volume (mm3) Testing the addition of an HSP90 inhibitor to hormonal therapy Ganetespib induces regression in tumors progressing on fulvestrant Days of treatment Fulvestrant ER+ and HER2negative breast cancer Fulvestrant + ganetespib Fulvestrant + ganestespib
- 18. Testing the role of Herceptin in Patients with HER-2 negative breast cancer who have HER2-positive CTCs Consent Blood sample Test CTCs Consider clinical trial of herceptin plus chemotherapy
- 19. Testing the role of Neratinib in Patients with HER2-negative breast cancer with a HER2 mutation Consent Retrieve archival tumor sample Sequence for HER2 Only 1.6% of HER2-negative breast cancer ? More common in lobular cancers Consider clinical trial of neratinib
- 20. Triple-Negative Breast Cancer Is Not All the Same Disease Lehmann et al, JCI 2011
- 21. Targeting the Androgen Receptor in Triple Negative Breast Cancer T Consent T Enzalutamide Retrieve archival tumor sample AR Cell cytoplasm Enzalutamide Cell nucleus Test for AR expression Consider clinical trial of enzalutimde AR Enzalutamide
- 22. Targeting the PI3Kinase Pathway Polyak and Filho, Cancer Cell, 2012
- 23. Targeting the PI3Kinase Pathway Polyak and Filho, Cancer Cell, 2012
- 24. Targeting the PI3Kinase Pathway • BKM120 for Triple-negative breast cancer • GDC0032 + Taxane for ER+ or Triple-negative • Taxol +/- GDC0941 for ER+ breast cancer • BYL719 + endocrine therapy for ER+ breast cancer
- 25. Targeting Cell Survival Pathways Chemotherapy IAPs
- 26. Targeting Cell Survival Pathways Chemotherapy IAPs
- 27. Helping Clinicians Keep Track of the Complexity
- 29. Summary • Not all breast cancers are alike • We have many clues • But we need clinical trials and continued basic and translational research to make new breakthroughs that reach patients
- 30. Acknowledgments • • • • • • • • • • • • • • • • • Eric Winer Ian Krop Sara Tolaney Erica Mayer Rachel Freedman Beth Overmoyer Ann Partridge William Barry Rebecca Gelman Julie Najita Otto Metzger Ines Vaz-Luis Davinia Seah Nadine Tung Steve Isakoff Dejan Juric Aditya Bardia • • • • • • • • • • • • • • • • Sairah Mahmud Max Lloyd Kate Cohen Carolyn Curley Kate Zeghibe Veronica Figueroa Kristen Filauro Sarah Galler Sarah Farooq Emily Schlosnagle Chelsea Andrews Jessica Sohl Nicole Ryabin Jennifer Savoie Elizabeth Frank Fran Smith • • • • • • • • • • • • • • • • Andrea Richardson Jane Brock Nelly Polyak Luke Whitesell Jean Zhao Myles Brown Nick Wagle Neal Lindeman Barrett Rollins Phil Kantoff Levi Garraway Keith Ligon Tom Roberts Elgene Lim Shom Goel Sandro Santagata
Notes de l'éditeur
- Top panel: ductal cancer, lower panel, lobular cancer
- Mention erica’s trial
- The vision, then, is that EVERY patient will have his or her tumor biopsied (*) and profiled for relevant DNA alterations (*) to get a somatic mutation signature(*). That profile will be provided to the oncologist and matrixed together with the repertoire of therapeutic agents (*) to come up with a treatment decision (*)(*) (a decision that is informed by the biology in addition to the anatomic origin of the tumor)
- Inhibits binding of androgens to AR, inhibits nuclear translocation of AR, inhibits AR mediated DNA binding
- LCL161 + taxol for pts with taxane refractory disease
- LCL161 + taxol for pts with taxanerefractory disease