The information in this slide show is the intellectual property of James Waisman, M.D. Written permission is required to use content found in this document.

1. San Antonio Breast Cancer
Symposium: update
CANCER SUPPORT COMMUNITY
JANUARY 15, 2013
PRESENTED BY : JAMES R WAISMAN, MD
BREASTLINK MEDICAL GROUP

2. My Goal
This is a patient perspective not a scientific presentation
asking you to look at data, however to understand the
difference between;
 Anecdote: Soy made me feel better
 Observation: Soy made a group of women feel better
 Data: There is evidence based on scientific analysis of data
that soy decreased menopause symptoms. The evidence is
validated, confirmed and statistically significant

3.  Nature of The Abstract
 Findings
 Significance

4. Introduction
 Why / What about San Antonio?
Most significant Breast Cancer Conference for
updates in research from a clinical & basic science
perspective
 Paradigm Shifts
Major Breakthroughs that impact clinical care
usually are first presented/discussed at San Antonio

5. My Goal
 Get a sense about the overall direction of
science
 What is the clinical relevance to you!
 What is the hope for the future
 How to empower you with knowledge to help
in your own advocacy!

6. S1-1: Relative effectiveness of letrozole compared with tamoxifen for
patients with lobular carcinoma in the BIG 1-trial
 Methods: Randomized Phase III Trial comparing 5 years
of Tamoxifen to 5 years of Letrozole
 Conclusion:
Letrozole is superior to tamoxifen
Letrozole significantly superior to tamoxifen for infiltrating
lobular cancer
Letrozole is significatnly superior to tamoxifen for Luminal B
Letrozole is equal to tamoxifen for Luminal A

7. S1-1: Relative effectiveness of letrozole compared with tamoxifen for
patients with lobular carcinoma in the BIG 1-trial
 Paradigm Shift: Manage different Based on subgroup

8. S1-2-ATLAS- 10 vs 5 years of adjuvant tamoxifen in ER+ disease :
Effects on outcome in the first and in the second decade
1996-2005 6,846 women randomized to 5 vs 10 years
Results:
 80 % compliance
 Average follow up – 7.1 years
 10 years of tamoxifen is superior to 5 in all subgroups
 No increase of non-breast cancer mortality
 Continue reduction in recurrence in both 1st and 2nd decade
 With 80% compliance 10 years of tamoxifen will reduce breast cancer
mortality by 1/3

9. S1-2-ATLAS- 10 vs 5 years of adjuvant tamoxifen in ER+ disease :
Effects on outcome in the first and in the second decade
 Paradigm Shift:
10 years of tamoxifen is the new standard
Options:
• 10 years of tamoxifen
• 5 years of tamoxifen followed by an AI
(letrozole, exemestane)
• 2-3 years of tamoxifen followed by an AI
• 5 years of an AI followed by prolonged AI-post menopausal
women
• Manage by subtype?

10. S1-6: Results of a randomized phase 2 study of PD 0332991 a cyclin dependant kinase (CDK) 4/6
inhibitor, on combination with letrozole vs letrozole alone for First-line treatment of ER + /HER2-
advanced breast cancer
 Method: Blocks cell-cycle progression
 Results: Letrozole Letrozole + PD 033291
RR 26% 39%
CB 44% 70%
PRS 7.5 months 26.1 months
 Side effects: mild neutropenia, anemia , fatigue

11. S1-6: Results of a randomized phase 2 study of PD 0332991 a cyclin dependant kinase (CDK) 4/6
inhibitor, on combination with letrozole vs letrozole alone for First-line treatment of ER + /HER2-
advanced breast cancer
 Paradigm Shift:
A new way to exploit ways to overcome hormones
resistance
A robust clinical benefit
Minimal interference with QOL

12. S 1-7: Phase III trial evaluating the addition of bevacizumab to endocrine therapy as First-
line treatment for advanced breast cancer-First efficacy results from the LEA study
 Background: Preclinical data shows the high VEGF levels
are associated with a decreased response to
endocrine therapy
 Methods: Phase 3 using Bev every 3 weeks and letrozole
or fulvestrant as First line for metastatic breast cancer
ER + /Her2, 380 patients were randomized

13. S 1-7: Phase III trial evaluating the addition of bevacizumab to endocrine therapy as First-
line treatment for advanced breast cancer-First efficacy results from the LEA study
 Results: no clinical benefit to the addition of BEV
 Paradigm Shift:
Adds to other major negative trial (BEATRICE) for
addition of BEV
Supports FDAs position to “disapprove” BEV for
metastatic Breast cancer
Research needs to report negative trials

14. S1-9: Comparative Performance of Breast Cancer Index (BCI) vs Oncotype DX and IHC4 in the prediction
of late recurrence in hormone receptor + lymph node – breast cancer patients: a Trans ATAC study
 Background: Patients with ER + Breast cancer have late
recurrences extending to 15 years and beyond. More that
½ of recurrences happen after 5 years.
 Oncotype DX and IHC4 good at predicting early
recurrences but not clear about late recurrences
 Method: Compare BCI, Oncotype Dx and IHC4 for
predicting early and late recurrences

15. S1-9: Comparative Performance of Breast Cancer Index (BCI) vs Oncotype DX and IHC4 in the prediction
of late recurrence in hormone receptor + lymph node – breast cancer patients: a Trans ATAC study
 Results: All indices good for predicting recurrences
early, 0-5 years; only BCI was good at predicting late
recurrences 5-10 years.
 Paradigm Shift:
Need tools that help us with late recurrences so we can
indentify patients needing longer endocrine therapy
HOX B13 and IL 17-BR-Ret (gene signatures in BCI) may
be used in the future to predict late recurrences
Another step in the era of “personalized” therapy

16. S1-10: Association between the 21 gene recurrence score (Oncotype DX) and benefit from adjuvant
paclitaxel in node-positive, ER positive breast cancer patients:
Results from NSABP B-28
 Method: Compare AC (adriamycin/cytoxan) vs ACT
(AC + paclitaxel {taxol})
 Results:
RS predicts for lack of any chemo benefit in the low RS
group
RS does not discriminate pac/taxol benefit in any
group (intermediate Or high)

17. S1-10: Association between the 21 gene recurrence score (Oncotype DX) and benefit from adjuvant
paclitaxel in node-positive, ER positive breast cancer patients:
Results from NSABP B-28
 Paradigm Shift:
Another study confirming lack of chemo benefit in
N + in addition To N-group
Molecular sub types is the new “trump” card for chemo
vs hormone benefit in adjuvant, neoadjuvant,
metastatic patients

18. S1-11: Meta Analysis Results from the Collaborative Trials in Neoadjuvant
Breast Cancer
 Background:
Looking for surrogate end points of survival
Is pCR (complete pathologic response the possible
endpoint)?
 Method: Look at 12 trials and 13, 125 patients

19. S1-11: Meta Analysis Results from the Collaborative Trials in Neoadjuvant
Breast Cancer
Results:
 Elimination of tumor from both breast and lymph node better than
elimination from breast alone in terms of survival
 Presence of DCIS didn’t influence outcome
 pCR uncommon in low grade tumors – 7%
 pCR more common in 3X negative (34%) and HER 2 +/ER+ 30%,
High grade ER+(16%), ER-/HER2 + (50%)
 Too heterogeneous to know the optimal regimen

20. S1-11: Meta Analysis Results from the Collaborative Trials in Neoadjuvant
Breast Cancer
Paradigm Shift:
 Neoadjuvant therapy is the future clinical approach to optimize best
therapy and needs to be selected based on subtype
 Need more research-based clinical trials to define optimal therapy
 Need a multidisciplinary team to see and decide as to optimal therapy
 There is no survival “disadvantage” to treat with chemo or hormones
first and there may be a survival advantage in doing chemo/hormones
first

21. S4-1 The UK Start (Standardization of Breast Radiotherapy) Trials:
10 year follow up results
Method:
 Standard dose is 50 Gy in 25 doses
 Randomized to 50Gy in 25 dose over 5 weeks, vs 41.6 or
39Gy in 13 for over 5 weeks (START A) or 40Gy in 15 for
over 3 weeks (START B)

22. S4-1 The UK Start (Standardization of Breast Radiotherapy) Trials:
10 year follow up results
Results:
 Outcome is local recurrence rate and tissue results
 Follow up is 9.3 years
 Outcomes for all groups were similar
 40 Gy over 15 fractions is standard of care in UK

23. S4-1 The UK Start (Standardization of Breast Radiotherapy) Trials:
10 year follow up results
Paradigm Shift:
Multiple options:
 50 Gy over 5 weeks with boost
 50 Gy over 5 weeks with no boost
 40 Gy over 3 weeks with or without boost
 Balloon catheter radiation (Mammosite, Savvy) 2x/day over 5 days
 IORT (on protocol-XOFT, off protocol Zeiss/Mobitron)
 Radiation therapists should be part of the
interdisciplinary treatment –seeing patients BEFORE
final treatment decision.

24. S4-2 Targeted intraoperative radiotherapy for early breast cancer:
TARGIT -A trial- updated analysis of local recurrence and first analysis of survival
Method:
 Phase III trial comparing standard dose xrt over 3 weeks
vs IORT
 3,451 women

25. S4-2 Targeted intraoperative radiotherapy for early breast cancer:
TARGIT -A trial- updated analysis of local recurrence and first analysis of survival
Results:
 1,721 had TARGIT
 1,010 – 4 year follow up
 611 – 5 year follow up
 Slight higher local recurrence at 5 years for TARGIT – 2%
difference
 Non-significant trend for increase in survival from TARGIT
due to fewer non-cancer deaths, cardiac 10 vs 1 and deaths
from other cancer 7 vs 16
 IORT done pre-pathology did slightly better than when
IORT was done post-pathology

26. S4-2 Targeted intraoperative radiotherapy for early breast cancer:
TARGIT -A trial- updated analysis of local recurrence and first analysis of survival
Paradigm Shift:
 IORT is appropriate for patients meeting the eligibility
criteria
 May be mechanistic reasons such as intraoperative
radiation killing growth factors release in fluid at the time
of surgery that also contributes to survival benefit, needs
more study.

27. S4-3: The EndoPredict Score identifies late distant metastasis in
ER +/Her2 – breast cancer patients
 Method:
The EP Score incorporates expression levels of
proliferative and ESR-1 genes evaluated in the
ABCSG6 and 8 Phase 3 Trials
 Results:
EP Score is an independent predictor of late recurrence
along with Size and Node status
There are 8 genes in this test

28. S4-3: The EndoPredict Score identifies late distant metastasis in
ER +/Her2 – breast cancer patients
Paradigm Shift:
 Another tool to help identify patients for late recurrence
needing longer therapy
 Another place of “personalized therapy” as described in
S1-9, S1-1

29. S5-2: HERA Trial: 2 years vs 1 year of trastuzumab after adjuvant chemotherapy
in women with HER 2 + early breast cancer at 8 year follow up
 Method:
Phase III trial
5,102 women randomized after surgery, chemo,
radiation to 2 vs 1 year of Trastuzumab
 Results:
1 year equal to 2 years

30. S5-2: HERA Trial: 2 years vs 1 year of trastuzumab after adjuvant chemotherapy in women
with HER 2 + early breast cancer at 8 year follow up
Paradigm Shift:
 1 year of Trastuzumab (Herceptin) is the accepted standard
of care
 1 year is equal to 2 years and superior to 6 months
(see PHARE Trial)

31. S5-3 : PHARE Trial results of subset analysis comparing 6 to 12 months of
trastuzumab in adjuvant early breast cancer
 Method: 3,382 women randomized after primary therapy
to 6 vs 12 months of Trastuzumab
 Results: 12 months was superior to 6 months
 Paradigm Shift: Along with HERA data the PHARE study
support 12 months as the appropriate length of
Trastuzumab therapy

32. S6-3: Neuro Cognitive impact in adjuvant chemotherapy for breast cancer linked
to fatigue: A prospective functional MRI study
Method:
 Women treated with adjuvant chemotherapy vs age
matched controls
 Patients performed a verbal working memory task during
functional MRI scanning

33. S6-3: Neuro Cognitive impact in adjuvant chemotherapy for breast cancer linked
to fatigue: A prospective functional MRI study
 Results:
Chemotherapy group reported greater severity of fatigue
Greater fatigue with poorer performance on post
treatment memory
Lower pre treatmnent motivation correlated best with
post treatment results
 Paradigm Shift: The pre treatment state is best predictor
of post treatment performance (fatigue & memory)

34. S6-4: Vitamin D, but not done turnover markers, predict relapse in women with
early breast cancer: an AZURE Translational Study
Method:
 872 AZURE patients on Zoledronic Acid
 Measure Vitamin D and bone-turnover markers

35. S6-4: Vitamin D, but not done turnover markers, predict relapse in women with
early breast cancer: an AZURE Translational Study
Results:
 High pre-treatment levels of 25- Hydroxy vitamin D are
associated with lower risk of recurrence
 High vitamin D predicts benefits to Zoledronic Acid
Bone-turnover marker are not predictive