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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New Breast Cancer Research & Clinical Trials for ER+ & TNBC
1. Whatâs New in Metastatic
Research and Clinical Trials:
ER Positive and Triple-Negative
Breast Cancer
Nancy Lin, MD
Susan F. Smith Center for Womenâs Cancers
Dana-Farber Cancer Institute
October 5, 2013
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*
â˘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
â˘Metastatic breast cancer
â˘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
âtailorâ treatments?
2. Which molecular features are important and
which are just âalong 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 subtypesâŚ
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
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
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
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
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
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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
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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
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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
Hinweis der Redaktion
Top panel: ductal cancer, lower panel, lobular cancer
Mention ericaâs 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)Â
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