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Dana-Farber Cancer Institute Metastatic Breast Cancer Forum 2016

An overview of what was discussed at the 2016 Metastatic Breast Cancer Forum, held by Dana-Farber Cancer Institute.

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Dana-Farber Cancer Institute Metastatic Breast Cancer Forum 2016

  1. 1. Dana-Farber Cancer Institute Metastatic Breast Cancer Forum 2016 Research update for HER2-positive breast cancer Shom Goel MD PhD Instructor in Medicine, Harvard Medical School September 24, 2016
  2. 2. What is HER2-positive breast cancer? • 15-20 percent of breast cancer is “HER2-positive” Abundance of HER2 protein on cancer cells “Amplification” of the HER2 gene in tumor cells
  3. 3. HER2-positive metastatic breast cancer Relapse after treatment for early stage breast cancer “De novo” metastatic breast cancer
  4. 4. How is HER2-positive MBC treated? • The primary treatment of HER2-positive MBC is with systemic medical therapy – i.e. drugs • Surgery and radiotherapy may play a role in specific situations
  5. 5. FDA-approved drugs for HER2-positive MBC Herceptin (Trastuzumab, 1998) Perjeta (Pertuzumab, 2012) Lapatinib (Tykerb, 2005)
  6. 6. FDA-approved drugs for HER2-positive MBC Kadcyla (T-DM1, 2013) Perjeta (Pertuzumab, 2012) Lapatinib (Tykerb, 2005)
  7. 7. FDA-approved drugs for HER2-positive MBC Perjeta (Pertuzumab, 2012) Lapatinib (Tykerb, 2005)
  8. 8. FDA-approved drugs for HER2-positive MBC Perjeta (Pertuzumab, 2012) Lapatinib (Tykerb, 2005)
  9. 9. The main issue we face today is drug resistance • In many (not all) situations, HER2-positive MBC will respond well to existing therapies • However, over time cancer cells develop resistance to existing therapies • If we could completely overcome drug resistance, the disease would become chronic and/or curable
  10. 10. What causes treatment resistance? Growing in certain locationsTumor heterogeneity Turning off the immune systemChanges in “cell signaling”
  11. 11. How can we study treatment resistance? In cells In mice In our patients • Information from clinical trials • Biopsies of drug resistant tumors
  12. 12. Two examples from our laboratory (1) Resistant tumor cells respond to the CDK4/6 inhibitor abemaciclib Cyclin D1 A new transgenic mouse model of HER2-positive breast cancer Goel et al Cancer Cell 2016
  13. 13. Combination of Herceptin and abemaciclib overcomes drug resistance Patient-derived xenograft Days *** ** * 0 5 10 15 Foldchangein tumorvolume 0 2 4 Control Trastuzumab Abemaciclib Trast/Abema Goel et al Cancer Cell 2016
  14. 14. Two examples from our laboratory (2) Patient-derived models of HER2-positive brain metastasis Ni, Ramkissoon, Xie et al Nature Medicine 2016
  15. 15. Updates from our laboratory • Both of these findings are being translated into clinical trials for patients
  16. 16. New agents on the horizon • PI3-kinase inhibitors • CDK4/6 inhibitors • Immune therapies • New HER2 inhibitors • mTOR inhibitors • Antibody-drug conjugates Progress is real and continuing We have every reason to be optimistic
  17. 17. Thanks for your attention

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