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CSC-RB 1.15.2013
 

CSC-RB 1.15.2013

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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.

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.

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  • Nature of The AbstractFindingsSignificance

CSC-RB 1.15.2013 CSC-RB 1.15.2013 Presentation Transcript

  • San Antonio Breast Cancer Symposium: updateCANCER SUPPORT COMMUNITY JANUARY 15, 2013 PRESENTED BY : JAMES R WAISMAN, MD BREASTLINK MEDICAL GROUP
  • 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
  •  Nature of The Abstract Findings Significance
  • 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
  • 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!
  • 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
  • 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
  • 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 yearsResults: 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
  • 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?
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • S1-11: Meta Analysis Results from the Collaborative Trials in Neoadjuvant Breast CancerResults: 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
  • S1-11: Meta Analysis Results from the Collaborative Trials in Neoadjuvant Breast CancerParadigm 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
  • S4-1 The UK Start (Standardization of Breast Radiotherapy) Trials: 10 year follow up resultsMethod: 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)
  • S4-1 The UK Start (Standardization of Breast Radiotherapy) Trials: 10 year follow up resultsResults: 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
  • S4-1 The UK Start (Standardization of Breast Radiotherapy) Trials: 10 year follow up resultsParadigm 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.
  • S4-2 Targeted intraoperative radiotherapy for early breast cancer: TARGIT -A trial- updated analysis of local recurrence and first analysis of survivalMethod:  Phase III trial comparing standard dose xrt over 3 weeks vs IORT  3,451 women
  • S4-2 Targeted intraoperative radiotherapy for early breast cancer:TARGIT -A trial- updated analysis of local recurrence and first analysis of survivalResults: 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
  • S4-2 Targeted intraoperative radiotherapy for early breast cancer:TARGIT -A trial- updated analysis of local recurrence and first analysis of survivalParadigm 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.
  • 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
  • S4-3: The EndoPredict Score identifies late distant metastasis in ER +/Her2 – breast cancer patientsParadigm 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
  • 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
  • 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 upParadigm 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)
  • 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
  • S6-3: Neuro Cognitive impact in adjuvant chemotherapy for breast cancer linked to fatigue: A prospective functional MRI studyMethod: Women treated with adjuvant chemotherapy vs age matched controls Patients performed a verbal working memory task during functional MRI scanning
  • 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)
  • S6-4: Vitamin D, but not done turnover markers, predict relapse in women with early breast cancer: an AZURE Translational StudyMethod: 872 AZURE patients on Zoledronic Acid Measure Vitamin D and bone-turnover markers
  • S6-4: Vitamin D, but not done turnover markers, predict relapse in women with early breast cancer: an AZURE Translational StudyResults: 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