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

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. 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. HER2-positive metastatic breast cancer
Relapse after treatment for early stage breast cancer
“De novo”
metastatic breast cancer

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. FDA-approved drugs for HER2-positive MBC
Herceptin
(Trastuzumab, 1998) Perjeta
(Pertuzumab, 2012)
Lapatinib
(Tykerb, 2005)

6. FDA-approved drugs for HER2-positive MBC
Kadcyla
(T-DM1, 2013) Perjeta
(Pertuzumab, 2012)
Lapatinib
(Tykerb, 2005)

7. FDA-approved drugs for HER2-positive MBC
Perjeta
(Pertuzumab, 2012)
Lapatinib
(Tykerb, 2005)

8. FDA-approved drugs for HER2-positive MBC
Perjeta
(Pertuzumab, 2012)
Lapatinib
(Tykerb, 2005)

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. What causes treatment resistance?
Growing in certain locationsTumor heterogeneity
Turning off the immune systemChanges in “cell signaling”

11. How can we study treatment resistance?
In cells In mice
In our patients
• Information from clinical trials
• Biopsies of drug resistant tumors

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. 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. Two examples from our laboratory (2)
Patient-derived models of HER2-positive brain metastasis
Ni, Ramkissoon, Xie et al Nature Medicine 2016

15. Updates from our laboratory
• Both of these findings are being translated into
clinical trials for patients

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. Thanks for your attention