(Neo-) adjuvant endocrine therapy

Size: px
Start display at page:

Download "(Neo-) adjuvant endocrine therapy"

Transcription

1

2 (Neo-) adjuvant endocrine therapy F. Cardoso, MD Director, Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal ESO Breast Cancer Program Coordinator ESMO Board of Directors & NR Committee Chair EORTC Breast Group Past-Chair

3 DISCLOSURES Consultant/Ad Board: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Seattle Genetics, Teva

4 ESMO Early Breast Cancer Guidelines 2015 (new version to be published in 2018!) St. Gallen 2017 Escalating and de-escalating treatment in Early Breast Cancer across subtypes and treatment modalities Early Breast Cancer Trialists Collaborative Group (EBCTCG) ( Oxford Overview )

5 EARLY BREAST CANCER: WHO NEEDS ADJUVANT ET? (almost) All ER+ EARLY BREAST CANCER patients! Until the early 90 s: decision was based on menopausal status: All post-menopausal: Yes All pre-menopausal: No

6 HR the only predictive factors Levels of positivity also important EBCTCG, The Lancet 2011

7 PREDICTIVE MARKERS FOR ENDOCRINE THERAPY ER (Tam and AIs) PgR (Tam and AIs) HER-2 PROLIFERATION (Ki67) Bcl-2 (Tam) AIB-1 (Tam) ER-beta (Tam) MTA1s (Tam) Cyclin E (Tam) HR are the only predictive factors with Level 1 evidence for ET NO BIOMARKER CAN HELP DECIDE BETWEEN TAM & AI Intratumoral Aromatase (AIs) Genomic signatures ESR1 mutations

8 WHICH TYPE OF ENDOCRINE THERAPY? Messages from the EBCTCG overview & individual trials Efficacy of 5 years Tam 9% ABSOLUTE BENEFIT Study Treatment arms/ Population (n) Tamoxifen 5 years Overview TAM 5 y vs no TAM 2011[76] ER+ Median FU Recurrence 15 y RR 0.53 [SE 0.03] years 0 4 RR 0.68 [SE 0 06] years 5 9 2p< RR 0.97 [SE 0.10] years Mortality RR 0.71 [SE 0.05] years 0 4, RR 0.66 [SE 0.05] years 5 9 RR 0.68 [SE 0.08] years p< CARRY-OVER EFFECT MCBS: A Ribeiro, Sousa and Cardoso, ECCO-ESMO 2013 Educational Book

9 Annual hazard rates (%) Time to recurrence: smoothed hazard estimates HR+ patients Tamoxifen (T) Anastrozole (A) Follow-up time (years) In the HR+ subgroup, the absolute difference in recurrence increased from 2.8% after 5 years to 4.8% after 9 years 0.0 There is a statistically significant larger carryover effect for anastrozole (HR=0.75, 95% CI , p=0.01)

10 WHICH TYPE OF ENDOCRINE THERAPY? Messages from the EBCTCG overview & individual trials Efficacy of Aromatase Inhibitors: Upfront Study AIs 5 years ATAC Treatment arms/ Population (n) TAM 5y vs ANA 5y 3116/ 3125 BIG 1.98 TAM 5y vs LET 5y 2459/ 2463 TEAM EXE 5y vs TAM 2-3y followed EXE 2-3y 4868/4898 Metaanalysis Cohort 1 AIs initial monotherapy vs TAM MA.27 9,856 EXE 5y vs ANA 5y 7,576 Median FU 120 months Recurrence HR= 0 91 (95% CI ) p = HR=0 88 (95% CI ) months p = y HR=0 97 ( ) p= y 9.6% AI v 12.6% TAM 2.9% absolute decrease (SE 0.7%) 2P < y HR=1.02 ( 95% CI, 0.87 to 1.18) P =0.85 Mortality 0.97 (95% CI ) p = 0 6 HR 0.87 (95% CI ) p = 0.08 HR=1.00 ( ) p> % AI v 5.9% TAM 1.1% (SE =0.5%) absolute decrease 2P =0.1 HR=0.93 ( 95% CI, ) P= 0.46 Ribeiro, Sousa and Cardoso, ECCO-ESMO 2013 Educational Book

11 Efficacy of Tam & Aromatase Inhibitors in Sequence Study Treatment arms/ Population (n) Median FU AIs and Tamoxifen in switching strategies BIG 1.98 LET 5 y 71 months TAM 2 y followed by LET 3 y ABCSG- 8/ARNO 95 LET 2 y followed by TAM 3 y 1546/ 1548/ 1540 TAM 5y vs Tam f 2y followed by ANA for 3 years ITA TAM 5y vs Tam f 2y followed by ANA IES TAM 5y vs Tam f 2-3y followed by EXE 2-3y Metaanalysis Cohort 2 AIs T after 2-3 y of TAM vs TAM 9, months 128 months 55 7 months Recurrence HR=1 05 (95% CI ) HR=0 96 (95% CI ) HR=0 60 ( ) p= HR=0 64 ( ) p = HR=0 76 (95% CI ) p= y 5.0% AI v 8.1% TAM 3.1% absolute decrease (SE 0.6%) 2P < Mortality HR=1.13 (95% CI ) HR=0.90 (95% CI ) p=0 16 HR=0.72 ( ) p = 0.3 HR (95% CI ) p= % AI v 2.4% TAM 0.7% (SE =0.3%) absolute decrease 2P =0.2 Ribeiro, Sousa and Cardoso, ECCO-ESMO 2013 Educational Book

12 GEICAM TRIAL HR+/HER2- postmenopausal patients with early breast cancer that have undergone surgery with or without neo/adjuvant chemotherapy R 872 pts 1:1 Anastrozole PO 1 mg daily for 5 years Stratification factors: No. of lymph nodes (0 vs. 1-3 vs. >4) (Neo)Adjuvant chemotherapy (yes vs. no) HR status (both positive vs. only one positive) Site Fulvestrant IM 500mg on day 0, 250mg day 14 and 28 and 250mg every 28 days thereafter for the first 3 years + Anastrozole PO 1mg/day for 5 years Courtesy of M. Ruiz-Borrego et al Primary endpoint: DFS Secondary endpoints: BCSS, OS, Safety, Time to recurrence

13 Disease Free Survival GEICAM TRIAL HR: ( ) Arm Event Total Anastrozole Anastrozole + Fulvestrant BC Specific Survival Anastrozole n = 437 Anastrozole + Fulvestrant n = 433 Total n = 870 Total number at risk Events Censored n (%) 372 (85.7) 368 (88.2) 740 (87.0) HR: ( ) Courtesy of M. Ruiz-Borrego et al Overall Survival Arm Event Total Anastrozole Anastrozole + Fulvestrant Anastrozole n = 437 Anastrozole + Fulvestrant n = 433 Total n = 870 Total number at risk Events Censored n (%) 387 (89.2) 378 (90.6) 765 (89.9) HR: ( ) Courtesy of M. Ruiz-Borrego et al Arm Event Total Anastrozole Anastrozole + Fulvestrant Anastrozole n = 437 Anastrozole + Fulvestrant n = 433 Total n = 870 Total number at risk Events Censored n (%) 400 (92.2) 389 (93.3) 789 (92.7) Courtesy of M. Ruiz-Borrego et al

14 WHICH DURATION OF ENDOCRINE THERAPY?

15 More than Half of all Breast Cancer Recurrences and Deaths Occur Post- 5y Tamoxifen Recurrences Breast cancer deaths 15% 17% 9% 18% % of patients Tamoxifen Control 54.9 % of patients Tamoxifen Control Years Years EBCTCG, Lancet. 2005

16 Annual Risk of Recurrence by ER Status 0.3 Recurrence hazard rate ER+ (n = 2257) ER (n = 1305) Over half of breast cancer recurrences occur >5 years post-surgery! The annual risk of late recurrence is particularly high in ER+ tumors (5.2% between years 5 and 8, 4.6% between years 8 and 12). Saphner T et al., J Clin Oncol Years Hormone receptor positivity is a strong predictor for late recurrence!

17 N Engl J Med 2017;377: Data from about 70,000 women with ER+ T1/T2, with 5 years of adjuvant ET

18 N Engl J Med 2017;377:

19 Meta-analysis on Five or More Years of Adjuvant Tamoxifen: Safety Profile Extended adjuvant Tamoxifen: Higher incidence of hot flushes, vaginal discharge and fluid retention. Higher incidence of thromboembolic events. Significant increase in endometrial carcinoma (OR 2.06, p< 0.001), absolute EBCTCG risk increase summary from 1.1 to 2.2%; 10 years without Tam significant vs 5 years influence on death from endometrial cancer. (at the current FU): Relative benefit: 15% Non- significant reduction in death from cardiovascular diseases (OR 0.89, p=0.25), absolute Absolute reduction from benefit: 3.2 to 2.8%; 3% No association between Increase extended in mortality: Tamoxifen and 0.4% other (nonendometrial) second cancers. Al-Mubarak M et al.,plos One 2014

20 MA.17: DFS by Menopausal Status Premenopausal (n=889) < 50 years of age with menses, but underwent subsequent bilateral oophorectomy or became amenorrhoic during adjuvant Cht or Tam. Postmenopausal (n=4,277) All patients HR= 0.57; p Premenopausal (n=889) Absolute benefit 10.1% HR = 0.25 p< Postmenopausal (n=4,277) Absolute benefit 3.3% HR = 0.69 p = Women who had been premenopausal at diagnosis experienced significantly greater benefit of extended letrozole in terms of DFS; significant interaction between treatment and menopausal status (p = 0.03). Goss PE et al. SABCS 2009; Goss PE et al., Ann Oncol 2013

21 San Antonio Breast Cancer Symposium - December 6-10, 2016 NSABP B-42: Schema Postmenopausal Pts with ER+ or PR+ Breast Cancer Stage I, II, or IIIa invasive BC at diagnosis Disease-free After 5 Years of Endocrine Therapy AI X 5 yrs or TAM X < 3 yrs AI to Complete 5 yrs Stratification: Pathological nodal status (Negative, Positive) Prior adjuvant TAM (Yes, No) Lowest BMD T score: spine, hip, femur (>-2.0, -2.0 SD) Letrozole X 5 yrs R Placebo X 5 yrs This presentation is the intellectual property of the author/presenter. Contact them at terry.mamounas@orlandohealth.com for permission to reprint and/or distribute.

22 Disease-Free Overall Survival Survival San Antonio Breast Cancer Symposium - December 6-10, 2016 NSABP B-42: Overall Survival Letrozole Placebo HR=1.15 ( ) # Deaths P= % 91.8% Years After Randomization After Randomization Letrozole Placebo This presentation is the intellectual property of the author/presenter. Contact them at terry.mamounas@orlandohealth.com for permission to reprint and/or distribute San Antonio Breast Cancer Symposium, December 6-10, 2016

23 Cum. Inc. of Arterial Thrombotic Events San Antonio Breast Cancer Symposium - December 6-10, 2016 NSABP B-42: Cum. Inc. of Arterial Thrombotic Events Cumulative Incidence of Osteoporotic Fx Letrozole Placebo Non-proportionality of Hazards for AT: p=0.007 HR=1.21 ( ) HR=0.55 p=0.054 # Events P=0.29 HR=1.85 P= % 3.4 % Years After Randomization This presentation is the intellectual property of the author/presenter. Contact them at terry.mamounas@orlandohealth.com for permission to reprint and/or distribute San Antonio Breast Cancer Symposium - December 6-10, 2016 NSABP B-42: Cumulative Incidence of Osteoporotic Fx Letrozole Placebo # Events HR=1.19 ( ) P= % % San Antonio Breast Cancer Symposium, December 6-10, Years After Randomization This presentation is the intellectual property of the author/presenter. Contact them at terry.mamounas@orlandohealth.com for permission to reprint and/or distribute

24 MA.17R Trial Schema and Design <br />AI x 5 yrs - Following Prior 5 years of AI - preceded or not by Tamoxifen Presented By Paul Goss at 2016 ASCO Annual Meeting

25 Slide 11 Presented By Paul Goss at 2016 ASCO Annual Meeting

26 Courtesy M. Gnant, SABCS 2016

27 EARLY BREAST CANCER: WHO NEEDS EXTENDED ADJUVANT ET? All ER+ EARLY BREAST CANCER patients with sufficient high risk??! No proven biomarker Role of some genomic signatures for determination of late relapses risk?! PAM 50 (Prosigna Breast Cancer Assay) Endopredict /Endopredict Clin Breast Cancer Index (BCI)

28 Estimated bone loss with AI s Comparing different strategies

29 Co-Morbidity & Side effects Arthralgia Endometrial polyp MBC UZ Leuven Abstr. 4056, Neuven et al

30 Surprisingly: Tam was worse than AI Also seen in the TEAM study

31 ADJUVANT ENDOCRINE THERAPY WITH AN A.I. : COMPLIANCE AND COST ISSUES Treatment with an AI will often necessitate: Earlier initiation of lipid-lowering drugs, antihypertensives and aspirin to reduce cardiac and cerebrovascular events Earlier initiation of medication for osteopenia/osteoporosis The use of pain medication, such as anti-inflammatory for myalgia / arthralgia Routine follow-up of lipids Monitoring of blood pressure Routine assessment of bone mineral density & frequently preventive therapy Courtesy of M. Trudeau

32 SOLE TRIAL: Study of letrozole extension after 4 to 6 years of prior adjuvant endocrine therapy postmenopausal, HR+, N+ Stratify Institution Prior ET: SERM AI Both R A N D O M I Z E Continuous letrozole x 5 yrs Intermittent letrozole over 5 yrs De-escalating 9 mos. 9 mos. 9 mos. 9 mos. 12 mos Patients Randomized in ITT, Nov July 2012 Presented ASCO, 2017 Courtesy M. Colleoni

33 SOLE PRIMARY ENDPOINT: DFS 60 mos. median follow-up Presented ASCO, 2017 Courtesy M. Colleoni

34 SOLE QUALITY OF LIFE: CHANGE FROM BASELINE TO 12 AND 24 MONTHS Presented ASCO, 2017 Courtesy M. Colleoni

35 ROLE OF OFS & AI IN PREMENOPAUSAL WOMEN TEXT & SOFT Trials TEXT and SOFT Trials: Comparison of Tamoxifen or Exemestane With OFS TEXT Premenopausal Patients with HR+ BC 12 wks after surgery (N = 2672) SOFT Stratified by trial, use of chemotherapy, nodal status Premenopausal patients with HR+ BC 12 wks after surgery (if no chemo) or 8 mos after chemo (N = 3066) Pagani O, et al. ASCO Abstract LBA1. Tamoxifen 20 mg/day + OFS* (n = 1328) Exemestane 25 mg/day + OFS* (n = 1332) Tamoxifen 20 mg/day + OFS* (n = 1016) Exemestane 25 mg/day + OFS* (n = 1014) Tamoxifen 20 mg/day 5 yrs Joint Analysis Tamoxifen + OFS* (n = 2344) Exemestane + OFS* (n = 2346) *OFS TEXT: triptorelin 3.75 mg IM every 28 days for 6 mos, then optional bilateral oophorectomy or irradiation SOFT: choice of method Pagani et al, N Engl J Med, 2014 Francis et al, N Engl J Med, 2015

36 San Antonio Breast Cancer Symposium, December 9-13, 2014 Outcomes from Premenopausal Adjuvant Chemotherapy Trials with no Hormonal Rx Goldhirsch A et al. JNCI Monogr 2001;30:44-51 ER-, <35 ER+, <35 ER-, 35+ ER+, Hazard Ratio of Relapse This presentation is the intellectual property of the presenter. Contact prue.francis@petermac.org for permission to reprint and/or distribute.

37 EBCTCG Ovarian Suppression/Ablation OFS/OFA Meta-analysis EBCTCG 2006 About 12% LESS RECURRENCES in PTS NOT TREATED WITH CT Not selected for ER!

38 CT DECISION WITH PHYSICIAN Francis et al, N Engl J Med, 2015

39 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 SOFT DFS 8 years median follow-up T+OFS significantly improves DFS vs T-alone in the overall population Francis et al, N Engl J Med, 2015 Updated at SABCS Fleming et al INTERNATIONAL BREAST CANCER STUDY GROUP This presentation is the intellectual property of IBCSG. Contact ibcsgcc@ibcsg.org for permission to reprint and/or distribute.

40 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 SOFT Secondary Endpoints Distant Recurrence-Free Interval Overall Survival A small overall survival benefit is seen with T+OFS vs T, at 8 yrs median follow-up Francis et al, N Engl J Med, 2015 Updated at SABCS Fleming et al INTERNATIONAL BREAST CANCER STUDY GROUP This presentation is the intellectual property of IBCSG. Contact ibcsgcc@ibcsg.org for permission to reprint and/or distribute.

41 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 SOFT Secondary Endpoints: No Chemo Distant Recurrence-Free Interval Overall Survival No Chemo cohort remains at low risk of distant recurrence with T alone; 12 of 24 deaths were in setting of no distant recurrence Francis et al, N Engl J Med, 2015 Updated at SABCS Fleming et al INTERNATIONAL BREAST CANCER STUDY GROUP This presentation is the intellectual property of IBCSG. Contact ibcsgcc@ibcsg.org for permission to reprint and/or distribute.

42 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 SOFT Secondary Endpoints: Prior Chemo Distant Recurrence-Free Interval Overall Survival Prior Chemo cohort has small absolute OS improvements in OFS arms at 8 yrs Francis et al, N Engl J Med, 2015 Updated at SABCS Fleming et al INTERNATIONAL BREAST CANCER STUDY GROUP This presentation is the intellectual property of IBCSG. Contact ibcsgcc@ibcsg.org for permission to reprint and/or distribute.

43 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 Protocol and Non-protocol Therapy T T + OFS E + OFS Stopped assigned oral endocrine therapy early 22.5% 18.5% 27.8% Stopped triptorelin early* 21.4% 19.6% Received OFS (in first 5 yrs) 15.5% Used oral endocrine therapy at 6 yr** 24.7% 24.3% 12.6% *and did not undergo oophorectomy or ovarian irradiation **as adjuvant therapy; denominator is patients alive and in follow-up at 6 yrs Francis et al, N Engl J Med, 2015 Updated at SABCS Fleming et al INTERNATIONAL BREAST CANCER STUDY GROUP This presentation is the intellectual property of IBCSG. Contact ibcsgcc@ibcsg.org for permission to reprint and/or distribute.

44 N=350 94% received CT Absolute improvement at 5 years HR (95% CI) T+OFS vs T E + OFS vs T BCFI 11,2% 15,7% Francis et al, N Engl J Med, 2015

45 SOFT Trial: CONCLUSIONS STRENGTHS: 1) LARGE, PROSPECTIVE, RANDOMIZED TRIAL 2) PRAGMATIC APPROACH TO USE OF CT 3) PROVIDES EVIDENCE THAT IN SOME PATIENTS WITH BETTER PROGNOSIS TAMOXIFEN ALONE IS A VERY GOOD TREATMENT 4) GIVES SUPPORT TO USE OF OFS IF NO AMENORRHEA IS OBTAINED WITH CT 5) HELPS DEFINING THE ROLE OF AIs IN PREMENOPAUSAL PATIENS, TOGETHER WITH THE TEXT TRIAL OPEN QUESTIONS: 1) PATIENTS RECEIVING CT (higher risk) WITH AMENORRHEA 2) PATIENTS RECOVERING MENSES AFTER 8 MONTHS 3) <35 years AND no need for CT 4) OPTIMAL DURATION OF OFS: are 5 years really necessary?

46 Combined analysis TEXT and SOFT Trials: Comparison of Tamoxifen or Exemestane With OFS TEXT Stratified by trial, use of chemotherapy, nodal status Premenopausal Patients with HR+ BC 12 wks after surgery (N = 2672) Tamoxifen 20 mg/day + OFS* (n = 1328) Exemestane 25 mg/day + OFS* (n = 1332) 5 yrs Joint Analysis Tamoxifen + OFS* (n = 2344) SOFT Premenopausal patients with HR+ BC 12 wks after surgery (if no chemo) or 8 mos after chemo (N = 3066) Tamoxifen 20 mg/day + OFS* (n = 1016) Exemestane 25 mg/day + OFS* (n = 1014) Tamoxifen 20 mg/day Exemestane + OFS* (n = 2346) *OFS TEXT: triptorelin 3.75 mg IM every 28 days for 6 mos, then optional bilateral oophorectomy or irradiation SOFT: choice of method Pagani et al, N Engl J Med, 2014

47 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 Exemestane With Ovarian Function Suppression Improves DFS 4.0% absolute improvement in 8-yr DFS for E+OFS after 9 years median follow-up INTERNATIONAL BREAST CANCER STUDY GROUP Pagani et al, N Engl J Med, 2014 Updated analysis: P. Francis and O. Pagani, SABCS 2017 This presentation is the intellectual This presentation property is the of the intellectual IBCSG. property Contact of ibcsgcc@ibcsg.org IBCSG. Contact ibcsgcc@ibcsg.org for permission to for reprint permission and/or to distribute. reprint and/or distribute.

48 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 Overall Survival E+OFS did not improve Overall Survival vs T+OFS, after 9 years median follow-up INTERNATIONAL BREAST CANCER STUDY GROUP Pagani et al, N Engl J Med, 2014 Updated analysis: P. Francis and O. Pagani, SABCS 2017 This presentation is the intellectual This presentation property is the of the intellectual IBCSG. property Contact of ibcsgcc@ibcsg.org IBCSG. Contact ibcsgcc@ibcsg.org for permission to for reprint permission and/or to distribute. reprint and/or distribute.

49 2017 SAN ANTONIO BREAST CANCER SYMPOSIUM December 5-9, 2017 Adverse Events and Treatment Adherence Incidence of grade 3-4 targeted AEs was similar in the two groups (32% and 31%) Overall, 15% of patients stopped all protocol-assigned treatment early More patients on E+OFS stopped assigned oral ET early 14% vs 6% by 1 year 25% vs 19% by 4 years No difference in the rate of triptorelin cessation 18% vs 19% by 4 years INTERNATIONAL BREAST CANCER STUDY GROUP Pagani et al, N Engl J Med, 2014 Updated analysis: P. Francis and O. Pagani, SABCS 2017 This presentation is the intellectual This presentation property is the of the intellectual IBCSG. property Contact of ibcsgcc@ibcsg.org IBCSG. Contact ibcsgcc@ibcsg.org for permission to for reprint permission and/or to distribute. reprint and/or distribute.

50

51 NEOADJUVANT ENDOCRINE THERAPY

52 Endocrine Therapy Neoadjuvant Clinical Trials (AI vs. Tam) P024 1 Drug Letrozole N 154 Clinical Response 55% US Response 35% Increase BCS P = % 4 months Tamoxifen % 25% 35% IMPACT 2 3 months Anastrozole Tamoxifen % 36% 24% 20% 46% 22% P =.03 Both % 28% 26% PROACT 3 Anastrozole % 40% 38% ns 3 months Tamoxifen % 35% 30% 1. Ellis M, et al. Breast Cancer Res Treat. 2007;105(Suppl 1): Smith IE, et al. J Clin Oncol. 2005;23(22): Cataliotti L, et al. Cancer. 2006;106(10):

53 Neoadjuvant Endocrine Therapy (AI vs. AI): ACOSOG Z1031 Trial Clinical Response, % Breast Conservation, % CR CR CR PR PR ML ML ML PR MO MO MO ML, marginal for lumpectomy; MO, mastectomy only at baseline Ellis M, et al. Cancer Res. 2010;70(24 Suppl): Abstract S1-2.

54 Sorlie et al PNAS 2001 pcr% with CT depends on cellular type and on molecular type N=22 10 pcr (45%) 61 genes signature N=20 9 pcr (45%) no signature identified N=28 2 pcr Rouzier et al. Clin Cancer Res 2005

55 Duration of Neoadjuvant Endocrine Therapy ³Exemestane Response to treatment as evaluated by mammography. OR, objective response; PD, progressive disease; SD, stable disease. ²Duration letrozole % CR 3 months months months 36 Conclusion: ¹ Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration 1 1. Paepke S, et al. BMC Cancer. 2008;8: Renshaw L, et al. Breast Cancer Res Treat. 2004;88(Suppl 1): Abstract Barnadas A, et al. Br J Cancer. 2009;100(3):

56 NEO-ADJUVANT ENDOCRINE THERAPY Is neoadjuvant endocrine therapy without cytotoxics a reasonable option for postmenopausal patients with endocrine responsive disease? YES 87.9% If yes, for which duration? weeks window prior to surgery 71% months 3.6% months 42.9% 4. Until maximal response 42.9% 9. Abstain 3.6%

57 Ki67 Changes With Endocrine Neoadjuvant Can Surrogate for Results in Adjuvant? Drug Comparison Neoadjuvant Trial Ki67 Results Adjuvant Trial Efficacy Results Let vs Tam P024 (n = 185) Mean 4 mos RFS L > T BIG 1-98 (n = 8010) L > T Ana vs Tam vs Tam+Ana IMPACT (n = 259) Mean 2/12 weeks: RFS A>T or AT ATAC (n = 9366) A > T or A+T Ana vs Let vs Exe ACOSOG Z1031 (n = 266) Mean weeks. No Diff MA 27 (n = 7576) A = E POTENTIAL PREDICTIVE ROLE OF CHANGE IN Ki67 AFTER NEOADJUVANT ET

58 PREOPERATIVE ENDOCRINE PROGNOSTIC INDEX (PEPI) Model built on only 158 pts P024 study Validated in 203 pts IMPACT study SOME LUMINAL A TUMORS BECAME LUMINAL B AFTER NEOADJUVANT AI May help decision of adjuvant therapy: PEPI Group 1 (0): No adjuvant CT needed PEPI Group 3 ( 4): Adjuvant CT needed PEPI Group 2 (1-3): unknown Ellis et al, JNCI 2008

59 Eligibility Post-menopausal Clinical Stage II or III ER+ (Allred 6-8) HER2- ALTERNATE Schema (A011106) BEFORE SURGERY AFTER SURGERY R E G I S T R A T I O N B I O P S Y R A N D O M I Z E Arm I Arm II Arm III 6 cycles (each cycle is 4 weeks) 4w 12 w B I O P S Y Ki67 <10% Ki67>10% Neoadjuvant Chemotherapy Group Chemotherapy of physician choice or weekly paclitaxel x 12 Cycle 1 day 2 optional biopsy (if receiving paclitaxel) Arm I Arm II Arm III S U R G E R Y Modified PEPI 0 Chemo NOT recommended Modified PEPI > 0 Chemo recommended Arm I A x 4.5 yrs Arm II F x 1.5 yrs then A x 3 yrs Arm III (A+F) x 1.5 yrs then Ax3 yrs Endocrine therapy of Physician s Choice Arm I: Anastrozole (A) Arm II: Fulvestrant (F) Arm III: Anastrozole + Fulvestrant F O L L O W F O L L O W SURGERY Red: required tissue collection Blue: optional tissue collection AFTER SURGERY Therapy of Physician Choice Primary Endpoints: 1 st Phase: Modified PEPI 0 rate 2 nd Phase: RFS in Modified PEPI 0 FOLLOW

60 WSG-ADAPT Trial: HR+ Subprotocol chemotherapy endocrine therapy Prognosis Corebiopsy (RS, Ki-67) Endocrine therapy 3 weeks Response Surgery / Corebiopsy (RS, Ki-67) Intermediate RS risk low proliferation response (Ki67 >10%) good proliferation response (Ki67 10%) endocrine therapy Principal investigators: N. Harbeck (LKP), Munich; U. Nitz, Mönchengladbach (courtesy Nadia Harbeck) Hofmann et al, Trials 2013

61 SURGERY**** Neoadjuvant (Ph 2): Adding Everolimus to Letrozole Improved Response Rates Primary endpoint: RR at 16 weeks (palpation) 270 Postmenopausal women with ER+ early BC R A N D O M I Z E Everolimus 10 mg/day + Letrozole 2.5 mg/day Placebo + Letrozole 2.5 mg/day Surgery neomonarch: Phase II study design Abemaciclib 150 mg BID is tolerable when dosed on a continuous schedule with endocrine therapy 1 The most common adverse event has been diarrhea Typically occurred within the first 7 days of treatment Manageable with use of loperamide or dose reduction Loperamide was administered prophylactically for the first 28 days then at discretion of investigator Anastrozole 1 mg QD Post-menopausal women (N=220) HR+, HER2- breast cancer stage: I (T 1 cm), II, IIIA or IIIB suitable for neoadjuvant endocrine therapy Core biopsy at baseline Randomization Abemacicliba 150 mg Q12H + anastrozole 1 mg QD Core biopsy after 2 weeks of treatment Primary endpoint: Compare the change from baseline in Ki67 expression after 2 weeks of therapy Abemaciclib a 150 mg Q12H + anastrozole 1 mg QD Abemaciclib a 150 mg Q12H Higher RR: 68% vs 59% (P = 0.062) Greater antiproliferative response: Ki67 by 57% vs 30% (P < 0.01) Abbreviations: BC, breast cancer; ER+, estrogen receptor-positive; Ph, phase; RR, response rate; vs, versus. Baselga J, et al. J Clin Oncol. 2009;27(16): Patnaik A et al. Cancer Discovery 2016;6:740-5 Core biopsy after 14 weeks of treatment b Surgery (optional) Abbreviations: HER2 = human epidermal growth factor receptor 2; HR = hormone receptor; Q12H = every 12 hours; QD = once daily a Participants receive loperamide with each dose of abemaciclib b Participants who experience benefit following 14 weeks may remain on neoadjuvant therapy for up to 8 additional weeks LETROZOLE AND PALBOCICLIB VERSUS 3 RD GENERATION CHEMOTHERAPY AS NEOADJUVANT TREATMENT OF LUMINAL BREAST CANCER. RESULTS OF THE UNICANCER - NEOPAL STUDY LORELEI STUDY DESIGN Newly diagnosed stage II-III BC* Biopsy ER+, HER2- Nodal status available** Prosigna Exclude non luminal tumors Luminal A N+ or Luminal B *Key inclusion criteria : post menopausal women; ER Allred 4; not candidate for breast conservation **FNA or biopsy; no SLN allowed ***Stratification factors (block permutation): T2 vs T3; Luminal A vs luminal B ****Surgery was performed 24h after the last palbociclib dosing R*** 1 : 1 Letrozole 2.5 mg/day + Palbociclib 125 mg/day, 3w/4 Cottu et al, ESMO weeks 3 FEC 100 fwd by 3 Docetaxel 100 (q3w) Untreated Postmenopausal Estrogen receptor (ER)- positive/her2-negative Stage I III operable BC 2 cm tumors by MRI STRATIFICATION FACTORS: Tumor size (T1 2 vs T3) Nodal status 1:1 KEY INCLUSION CRITERIA: Multifocal disease allowed Sample for centralized PIK3CA genotyping Fasting glucose 125 mg/dl KEY EXCLUSION CRITERIA: ct4 or cn3 stage BC Bilateral invasive or multicentric BC Excisional biopsy of primary tumor and/or sentinel lymph node biopsy prior to study treatment Stage IV BC Letrozole 2.5 mg QD + taselisib 4 mg (2 x 2 mg tablets) 5 days on/2 days off Tumor tissue Letrozole 2.5 mg QD + placebo 5 days on/2 days off Pre treatment MRI * Breast U/S Mammogram 16 weeks * Week 9: only required if suspicion of progression or if unevaluable by U/S at baseline S U R G E R Y 30-day safety follow-up, then investigator s choice of: adjuvant endocrine therapy and/or chemotherapy and/or radiotherapy Week 3 Week 9 Week 16 Surgery (Week 17 18) Saura et al, ESMO 2017

62 OPEN QUESTIONS No predictive markers to discriminate between Tam & AI Optimal duration for the individual patient (> 5 years ) Best strategy for extended adjuvant (10 y Tam; 10 y AI, sequence, sandwich, ) Role of ovarian suppression/ablation for the individual patient: STILL OPEN QUESTION until OS data; Optimal duration of OFS? Resistance!

(Neo-) adjuvant endocrine therapy

(Neo-) adjuvant endocrine therapy (Neo-) adjuvant endocrine therapy F. Cardoso, MD Director, Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal ESO Breast Cancer Program Coordinator ESMO Board of Directors & Chair NR Committee

More information

ORMONOTERAPIA ADIUVANTE: QUALE LA DURATA OTTIMALE? MARIANTONIETTA COLOZZA

ORMONOTERAPIA ADIUVANTE: QUALE LA DURATA OTTIMALE? MARIANTONIETTA COLOZZA ORMONOTERAPIA ADIUVANTE: QUALE LA DURATA OTTIMALE? MARIANTONIETTA COLOZZA THE NATURAL HISTORY OF HORMONE RECEPTOR- POSITIVE BREAST CANCER IS VERY LONG Recurrence hazard rate 0.3 0.2 0.1 0 ER+ (n=2,257)

More information

Adjuvant endocrine therapy (essentials in ER positive early breast cancer)

Adjuvant endocrine therapy (essentials in ER positive early breast cancer) Adjuvant endocrine therapy (essentials in ER positive early breast cancer) Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Experimental Therapeutics Outline Picking optimal adjuvant endocrine

More information

What is new in HR+ Breast Cancer? Olivia Pagani Breast Unit and Institute of oncology of Southern Switzerland

What is new in HR+ Breast Cancer? Olivia Pagani Breast Unit and Institute of oncology of Southern Switzerland What is new in HR+ Breast Cancer? Olivia Pagani Breast Unit and Institute of oncology of Southern Switzerland Outline Early breast cancer Advanced breast cancer Open questions Outline Early breast cancer

More information

William J. Gradishar MD

William J. Gradishar MD Northwestern University Feinberg School of Medicine Adjuvant Endocrine Therapy For Postmenopausal Women SOBO 2013 William J. Gradishar MD Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley

More information

Choosing between different hormonal therapies. Rudy Van den Broecke UZ Ghent

Choosing between different hormonal therapies. Rudy Van den Broecke UZ Ghent Choosing between different hormonal therapies Rudy Van den Broecke UZ Ghent What is the golden standard in premenopausal hormonal sensitive early breast cancer? Ovarian Suppression alone 5 years Tamoxifen

More information

38 years old, premenopausal, had L+snbx. Pathology: IDC Gr.II T-1.9cm N+2/4sn ER+100%st, PR+60%st, Her2-neg, KI %

38 years old, premenopausal, had L+snbx. Pathology: IDC Gr.II T-1.9cm N+2/4sn ER+100%st, PR+60%st, Her2-neg, KI % 38 years old, premenopausal, had L+snbx Pathology: IDC Gr.II T-1.9cm N+2/4sn ER+100%st, PR+60%st, Her2-neg, KI67 5-10% Question: What will you do now? 1. Give adjuvant chemotherapy 2. Send for Oncotype

More information

Manejo do câncer de mama RH+ na adjuvância: o que há de novo?

Manejo do câncer de mama RH+ na adjuvância: o que há de novo? II Simpósio Internacional de Câncer de Mama para o Oncologista Clínico Manejo do câncer de mama RH+ na adjuvância: o que há de novo? INGRID A. MAYER, MD, MSCI Assistant Professor of Medicine Director,

More information

Emerging Approaches for (Neo)Adjuvant Therapy for ER+ Breast Cancer

Emerging Approaches for (Neo)Adjuvant Therapy for ER+ Breast Cancer Emerging Approaches for (Neo)Adjuvant Therapy for E+ Breast Cancer Cynthia X. Ma, M.D., Ph.D. Associate Professor of Medicine Washington University in St. Louis Outline Current status of adjuvant endocrine

More information

Extended Hormonal Therapy

Extended Hormonal Therapy Extended Hormonal Therapy Dr. Caroline Lohrisch, Medical Oncologist, BC Cancer Agency Vancouver Centre November 1, 2014 www.fpon.ca Optimal Endocrine Therapy for Women with Hormone Receptor Positive Early

More information

OPTIMAL ENDOCRINE THERAPY IN EARLY BREAST CANCER

OPTIMAL ENDOCRINE THERAPY IN EARLY BREAST CANCER OPTIMAL ENDOCRINE THERAPY IN EARLY BREAST CANCER STEPHEN E. JONES, M.D. US ONCOLOGY RESEARCH THE WOODLANDS, TX TOPICS PREMENOPAUSAL BREAST CANCER POSTMENOPAUSAL BREAST CANCER THE FUTURE TOPICS PREMENOPAUSAL

More information

Luminal early breast cancer: (neo-) adjuvant endocrine therapy

Luminal early breast cancer: (neo-) adjuvant endocrine therapy CAMPUS GROSSHADERN CAMPUS INNENSTADT KLINIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE DIREKTOR: PROF. DR. MED. SVEN MAHNER Luminal early breast cancer: (neo-) adjuvant endocrine therapy Nadia

More information

Seigo Nakamura,M.D.,Ph.D.

Seigo Nakamura,M.D.,Ph.D. Seigo Nakamura,M.D.,Ph.D. Professor of Surgery Director of Breast Center Showa University Hospital Chairman of the board of directors Japan Breast Cancer Society Inhibition of Estrogen-Dependent Growth

More information

Early Stage Disease. Hope S. Rugo, MD Professor of Medicine Director Breast Oncology and Clinical Trials Education UCSF Comprehensive Cancer Center

Early Stage Disease. Hope S. Rugo, MD Professor of Medicine Director Breast Oncology and Clinical Trials Education UCSF Comprehensive Cancer Center SABCS 2014: Early Stage Disease Hope S. Rugo, MD Professor of Medicine Director Breast Oncology and Clinical Trials Education UCSF Comprehensive Cancer Center Topics for Discussion Chemotherapy plus 10

More information

Lessons Learnt from Neoadjuvant Hormone Therapy. 10 Lessons Learnt from Neoadjuvant Endocrine Therapy. Lesson 1

Lessons Learnt from Neoadjuvant Hormone Therapy. 10 Lessons Learnt from Neoadjuvant Endocrine Therapy. Lesson 1 Lessons Learnt from Neoadjuvant Hormone Therapy Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh 10 Lessons Learnt from Neoadjuvant Endocrine Therapy 10 Lessons Learnt from Neoadjuvant

More information

Lessons Learnt from Neoadjuvant Hormone Therapy. Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh

Lessons Learnt from Neoadjuvant Hormone Therapy. Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh Lessons Learnt from Neoadjuvant Hormone Therapy Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh 10 Lessons Learnt from Neoadjuvant Endocrine Therapy 10 Lessons Learnt from Neoadjuvant

More information

Update on New Perspectives in Endocrine-Sensitive Breast Cancer. James R. Waisman, MD

Update on New Perspectives in Endocrine-Sensitive Breast Cancer. James R. Waisman, MD Update on New Perspectives in Endocrine-Sensitive Breast Cancer James R. Waisman, MD Nothing to disclose DISCLOSURE TAILORx Oncotype Recurrence Score TAILORx Study Design Sparano, J Clin Oncol 2008;26:721-728

More information

Adjuvant Endocrine Therapy in Pre- and Postmenopausal Patients

Adjuvant Endocrine Therapy in Pre- and Postmenopausal Patients Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Adjuvant Endocrine Therapy in Pre- and Postmenopausal Patients Adjuvant Endocrine Therapy in Pre- and Postmenopausal Patients

More information

Lecture 5. Primary systemic therapy: clinical and biological endpoints

Lecture 5. Primary systemic therapy: clinical and biological endpoints Lecture 5 Primary systemic therapy: clinical and biological endpoints Valentina Guarneri, M.D., Ph.D. Primary systemic therapy in breast cancer Firstly introduced d into clinical i l practice in 70s for

More information

Should premenopausal HR+ve breast cancer receive LHRH?

Should premenopausal HR+ve breast cancer receive LHRH? Should premenopausal HR+ve breast cancer receive LHRH? Hesham Elghazaly, MD Prof. Clinical Oncology, Ain Shams University President of the BGICS Should premenopausal HR+ve breast cancer receive LHRH? NO?

More information

William J. Gradishar MD

William J. Gradishar MD Northwestern University Feinberg School of Medicine Adjuvant Endocrine Therapy For Postmenopausal Women SOBO 2011 William J. Gradishar MD Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley

More information

SOFTly: The Long Natural History of [Trials for] [premenopausal] ER+ Breast Cancer

SOFTly: The Long Natural History of [Trials for] [premenopausal] ER+ Breast Cancer SOFTly: The Long Natural History of [Trials for] [premenopausal] ER+ Breast Cancer Charles Moertel Lecture May 12, 2017 Gini Fleming Charles Moertel Founder of NCCTG Dedication to high quality clinical

More information

Metastatic breast cancer: sequence of therapies

Metastatic breast cancer: sequence of therapies Metastatic breast cancer: sequence of therapies Clinical Case Discussion Nadia Harbeck, MD PhD Breast Center, Department of Gynecology and Obstetrics University of Munich, Ludwig-Maximilians University

More information

Updates From San Antonio Breast Cancer Symposium 2017

Updates From San Antonio Breast Cancer Symposium 2017 Updates From San Antonio Breast Cancer Symposium 2017 Rob Coleman University of Sheffield Presentation Outline New Insights into adjuvant endocrine treatment Duration of treatment Perioperative therapy

More information

Hormone therapy in Breast Cancer patients with comorbidities

Hormone therapy in Breast Cancer patients with comorbidities Hormone therapy in Breast Cancer patients with comorbidities Diana Crivellari Centro di Riferimento Oncologico Aviano- ITALY Madrid November 9th, 2007 Main issues Comorbidities in elderly women Hormonal

More information

Endocrine Therapy in Premenopausal Breast Cancer. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology, PA US Oncology

Endocrine Therapy in Premenopausal Breast Cancer. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology, PA US Oncology Endocrine Therapy in Premenopausal Breast Cancer Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology, PA US Oncology Ovarian Ablation or Suppression vs. Not in ER + or ER UK Breast Cancer

More information

Extended Adjuvant Endocrine Therapy

Extended Adjuvant Endocrine Therapy Extended Adjuvant Endocrine Therapy After all, 5 years Tamoxifen works.. For women with ER+ primary breast cancer, previous studies have shown that treatment with tamoxifen for 5 years has a carry-over

More information

Best of San Antonio 2008

Best of San Antonio 2008 Best of San Antonio 2008 Ellie Guardino, MD/PhD Assistant Professor Stanford University BIG 1 98: a randomized double blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant

More information

Adjuvant Endocrine Therapy: How Long is Long Enough?

Adjuvant Endocrine Therapy: How Long is Long Enough? Adjuvant Endocrine Therapy: How Long is Long Enough? Harold J. Burstein, MD, PhD Dana-Farber Cancer Institute Harvard Medical School Boston, Massachusetts hburstein@partners.org I have no conflicts to

More information

The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now?

The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now? 1 The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now? Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program

More information

Current Optimal Sequence and Duration of Endocrine Treatment

Current Optimal Sequence and Duration of Endocrine Treatment [Symposium 7] Present and Future of Endocrine Therapy 07 Apr, 2018@GBCC Current Optimal Sequence and Duration of Endocrine Treatment Breast Oncology Center The Cancer Institute Hospital of JFCR Shinji

More information

NSABP Pivotal Breast Cancer Clinical Trials: Historical Perspective, Recent Results and Future Directions

NSABP Pivotal Breast Cancer Clinical Trials: Historical Perspective, Recent Results and Future Directions 1 1 NSABP Pivotal Breast Cancer Clinical Trials: Historical Perspective, Recent Results and Future Directions Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health

More information

Follow-up Care of Breast Cancer Patients

Follow-up Care of Breast Cancer Patients Follow-up Care of Breast Cancer Patients Dr. Simon D. Baxter, MD, FRCPC Medical Oncologist BC Cancer Kelowna Clinical Instructor, Dept of Medicine University of British Columbia 24 November 2018 Disclosures

More information

Кой има полза от адювантна ендокринна терапия при карцином на гърда с какво и колко дълго?

Кой има полза от адювантна ендокринна терапия при карцином на гърда с какво и колко дълго? Кой има полза от адювантна ендокринна терапия при карцином на гърда с какво и колко дълго? д-р Красимир Койнов МБАЛ Сердика, София Декларация Консултации и хонорари: Roche, Boerhinger Ingelheim, Astra

More information

8/8/2011. PONDERing the Need to TAILOR Adjuvant Chemotherapy in ER+ Node Positive Breast Cancer. Overview

8/8/2011. PONDERing the Need to TAILOR Adjuvant Chemotherapy in ER+ Node Positive Breast Cancer. Overview Overview PONDERing the Need to TAILOR Adjuvant in ER+ Node Positive Breast Cancer Jennifer K. Litton, M.D. Assistant Professor The University of Texas M. D. Anderson Cancer Center Using multigene assay

More information

MEDICAL ONCOLOGY NEWS IN BREAST CANCER 2014

MEDICAL ONCOLOGY NEWS IN BREAST CANCER 2014 MEDICAL ONCOLOGY NEWS IN BREAST CANCER 2014 Dr Thomas Yau Clinical Assistant Professor MBBS(HK), MRCP (UK), FHKCP (Med Onc), FHKAM( Medicine), FRCP(London) Queen Mary Hospital The University of Hong Kong

More information

Hormone therapyduration: Can weselectthosepatientswho benefitfromtreatmentextension?

Hormone therapyduration: Can weselectthosepatientswho benefitfromtreatmentextension? Hormone therapyduration: Can weselectthosepatientswho benefitfromtreatmentextension? Ivana Sestak, PhD Centre for Cancer Prevention Wolfson Institute of Preventive Medicine Queen Mary University London

More information

Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings. Eve Rodler, MD University of California at Davis October 2016

Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings. Eve Rodler, MD University of California at Davis October 2016 Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings Eve Rodler, MD University of California at Davis October 2016 17th Annual Advances in Oncology September 30-October 1, 2016

More information

Follow-up Care of Breast Cancer Patients

Follow-up Care of Breast Cancer Patients Follow-up Care of Breast Cancer Patients Dr. Simon D. Baxter, MD, FRCPC Medical Oncologist BC Cancer Kelowna Clinical Instructor, Dept of Medicine University of British Columbia 19 April 2018 Disclosures

More information

Endocrine Therapy 2017: Is There a Better Single Agent and when Should we Use it?

Endocrine Therapy 2017: Is There a Better Single Agent and when Should we Use it? Endocrine Therapy 2017: Is There a Better Single Agent and when Should we Use it? ET1 ET2 ET3 Targeted agent 1 Targeted agent 2 Hope S. Rugo, MD Director, Breast Oncology and Clinical Trials Education

More information

Locally Advanced Breast Cancer: Systemic and Local Therapy

Locally Advanced Breast Cancer: Systemic and Local Therapy Locally Advanced Breast Cancer: Systemic and Local Therapy Joseph A. Sparano, MD Professor of Medicine & Women s Health Albert Einstein College of Medicine Associate Chairman, Department of Oncology Montefiore

More information

Oncotype DX testing in node-positive disease

Oncotype DX testing in node-positive disease Should gene array assays be routinely used in node positive disease? Yes Christy A. Russell, MD University of Southern California Oncotype DX testing in node-positive disease 1 Validity of the Oncotype

More information

Mechanisms of Resistance to. Lisa A. Carey, M.D. University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

Mechanisms of Resistance to. Lisa A. Carey, M.D. University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Mechanisms of Resistance to Hormonal Therapy Lisa A. Carey, M.D. University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Antagonizing Estrogen Dependent Growth Premenopausal

More information

ESMO Breast Cancer Preceptorship Singapore November Special Issues in Treatment of Young Women with Breast Cancer

ESMO Breast Cancer Preceptorship Singapore November Special Issues in Treatment of Young Women with Breast Cancer ESMO Breast Cancer Preceptorship Singapore November 2017 Special Issues in Treatment of Young Women with Breast Cancer Prudence Francis MD Peter MacCallum Cancer Centre Melbourne, Australia Conflict of

More information

The Neoadjuvant Model as a Translational Tool for Drug and Biomarker Development in Breast Cancer

The Neoadjuvant Model as a Translational Tool for Drug and Biomarker Development in Breast Cancer The Neoadjuvant Model as a Translational Tool for Drug and Biomarker Development in Breast Cancer Laura Spring, MD Breast Medical Oncology Massachusetts General Hospital Primary Mentor: Dr. Aditya Bardia

More information

Sesiones interhospitalarias de cáncer de mama. Revisión bibliográfica 4º trimestre 2015

Sesiones interhospitalarias de cáncer de mama. Revisión bibliográfica 4º trimestre 2015 Sesiones interhospitalarias de cáncer de mama Revisión bibliográfica 4º trimestre 2015 Selected papers Prospective Validation of a 21-Gene Expression Assay in Breast Cancer TAILORx. NEJM 2015 OS for fulvestrant

More information

When is Chemotherapy indicated in Advanced Luminal Breast Cancer?

When is Chemotherapy indicated in Advanced Luminal Breast Cancer? When is Chemotherapy indicated in Advanced Luminal Breast Cancer? Soo-Chin Lee Head & Senior Consultant Department of Haematology-Oncology Clinical Care National University Cancer Institute, Singapore

More information

Long Term Toxicity of Endocrine Therapy for premenopausal women with ER positive breast cancer

Long Term Toxicity of Endocrine Therapy for premenopausal women with ER positive breast cancer Global Breast Cancer Conference 2017 21 st Apr, 2017@Chezu Island Long Term Toxicity of Endocrine Therapy for premenopausal women with ER positive breast cancer Shinji Ohno, M.D., Ph.D., F.A.C.S. Breast

More information

Terapia adiuvante con inibitori delle Kinasi Cliclina Dipendenti 4/6: quale futuro? Filippo Montemurro

Terapia adiuvante con inibitori delle Kinasi Cliclina Dipendenti 4/6: quale futuro? Filippo Montemurro Terapia adiuvante con inibitori delle Kinasi Cliclina Dipendenti 4/6: quale futuro? Filippo Montemurro Unit of Investigative Clinical Oncology Istituto di Candiolo (IRCCS) Disclosures Speaker s Honoraria

More information

Use of Ovarian Suppression and Ablation in Breast Cancer Treatment

Use of Ovarian Suppression and Ablation in Breast Cancer Treatment Use of Ovarian Suppression and Ablation in Breast Cancer Treatment Dr Marina Parton Consultant Medical Oncologist Royal Marsden and Kingston Hospitals Overview Breast cancer phenotypes Use of ovarian manipulation

More information

Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer

Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer Kathy S. Albain, MD, FACP Professor of Medicine Dean s Scholar Loyola University Chicago Stritch School of Medicine Cardinal Bernardin

More information

Integrated care: guidance on fracture prevention in cancer-associated bone disease; treatment options

Integrated care: guidance on fracture prevention in cancer-associated bone disease; treatment options Paris, November 1st 2016 Integrated care: guidance on fracture prevention in cancer-associated bone disease; treatment options René Rizzoli MD International Osteoporosis Foundation and Division of Bone

More information

The Oncotype DX Assay in the Contemporary Management of Invasive Early-stage Breast Cancer

The Oncotype DX Assay in the Contemporary Management of Invasive Early-stage Breast Cancer The Oncotype DX Assay in the Contemporary Management of Invasive Early-stage Breast Cancer Cancer The Biology Century Understanding and treating the underlying tumor biology Cancer genetic studies demonstrate

More information

Chemo-endocrine prevention of breast cancer

Chemo-endocrine prevention of breast cancer Chemo-endocrine prevention of breast cancer Andrea DeCensi, MD Division of Medical Oncology Ospedali Galliera, Genova; Division of Cancer Prevention and Genetics, European Institute of Oncology, Milano;

More information

Terapia Hormonal da Paciente Premenopausa

Terapia Hormonal da Paciente Premenopausa I Congresso de Oncologia D Or 5 e 6 de julho de 2013 Terapia Hormonal da Paciente Premenopausa Antonio C. Wolff, MD, FACP, FASCO Professor de Oncologia Programa de Câncer de Mama Johns Hopkins University

More information

Radiotherapy Management of Breast Cancer Treated with Neoadjuvant Chemotherapy. Julia White MD Professor, Radiation Oncology

Radiotherapy Management of Breast Cancer Treated with Neoadjuvant Chemotherapy. Julia White MD Professor, Radiation Oncology Radiotherapy Management of Breast Cancer Treated with Neoadjuvant Chemotherapy Julia White MD Professor, Radiation Oncology Agenda Efficacy of radiotherapy in the management of breast cancer in the Adjuvant

More information

Invasive Breast Cancer

Invasive Breast Cancer Invasive Breast Cancer Eileen Rakovitch MD MSc FRCPC Sunnybrook Health Sciences Centre Medical Director, Louise Temerty Breast Cancer Centre LC Campbell Chair in Breast Cancer Research Associate Professor,

More information

Considerations in Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology

Considerations in Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology Considerations in Adjuvant Chemotherapy Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology 80 70 60 50 40 30 20 10 0 EBCTCG 2005/6 Overview Control Arms with No Systemic Treatment

More information

A Slow Starvation: Adjuvant Endocrine Therapy of Breast Cancer

A Slow Starvation: Adjuvant Endocrine Therapy of Breast Cancer A Slow Starvation: Adjuvant Endocrine Therapy of Breast Cancer Dr. Susan Ellard Surgical Oncology Update October 24, 2009 Disclosure slide Participant in various meetings or advisory boards sponsored by

More information

NeoadjuvantTreatment In BC When, How, Who?

NeoadjuvantTreatment In BC When, How, Who? NeoadjuvantTreatment In BC When, How, Who? Clifford Hudis, M.D. Chief, Breast Cancer Medicine Service, MSKCC Professor of Medicine, Weill Cornell Medical College President, ASCO 15 Potential Benefits Of

More information

Gene Signatures in Breast Cancer: Moving Beyond ER, PR, and HER2? Lisa A. Carey, M.D. University of North Carolina USA

Gene Signatures in Breast Cancer: Moving Beyond ER, PR, and HER2? Lisa A. Carey, M.D. University of North Carolina USA Gene Signatures in Breast Cancer: Moving Beyond ER, PR, and HER2? Lisa A. Carey, M.D. University of North Carolina USA When Are Biomarkers Ready To Use? Same Rules for Gene Expression Panels Key elements

More information

Giuseppe Viale for the BIG 1 98 Collaborative and International Breast Cancer Study Groups

Giuseppe Viale for the BIG 1 98 Collaborative and International Breast Cancer Study Groups Central Review of ER, PgR and HER2 in BIG 1 98 Evaluating Letrozole vs. Letrozole Tamoxifen vs. Tamoxifen Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women with Hormone Receptor Positive

More information

Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers

Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers 日大医誌 75 (1): 10 15 (2016) 10 Original Article Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers Naotaka Uchida 1), Yasuki Matsui 1), Takeshi Notsu 1) and Manabu

More information

UK Interdisciplinary Breast Cancer Symposium. Should lobular phenotype be considered when deciding treatment? Michael J Kerin

UK Interdisciplinary Breast Cancer Symposium. Should lobular phenotype be considered when deciding treatment? Michael J Kerin UK Interdisciplinary Breast Cancer Symposium Should lobular phenotype be considered when deciding treatment? Michael J Kerin Professor of Surgery National University of Ireland, Galway and Galway University

More information

Objectives Primary Objectives:

Objectives Primary Objectives: Z1031 A randomized phase III trial comparing 16 to 18 weeks of neoadjuvant exemestane (25mg daily), letrozole (2.5mg), or anastrozole (1mg) in postmenopausal women with clinical stage II and III estrogen

More information

Rationale For & Design of TAILORx. Joseph A. Sparano, MD Albert Einstein College of Medicine Montefiore-Einstein Cancer Center Bronx, New York

Rationale For & Design of TAILORx. Joseph A. Sparano, MD Albert Einstein College of Medicine Montefiore-Einstein Cancer Center Bronx, New York Rationale For & Design of TAILORx Joseph A. Sparano, MD Albert Einstein College of Medicine Montefiore-Einstein Cancer Center Bronx, New York Declining Breast Cancer Mortality & Event Rates in Adjuvant

More information

XII Michelangelo Foundation Seminar

XII Michelangelo Foundation Seminar XII Michelangelo Foundation Seminar The opportunity of the neoadjuvant approach L. Gianni, Milan, I XII Michelangelo Foundation Seminar Milano, October 12, 2012 The opportunity of the neoadjuvant approach

More information

HORMONAL THERAPY IN ADJUVANT CARE

HORMONAL THERAPY IN ADJUVANT CARE ADVANCES IN ENDOCRINE THERAPY FOR BREAST CANCER* Matthew J. Ellis, MD, PhD ABSTRACT Endocrine therapy is used frequently in breast cancer management, particularly in the setting of adjuvant care, but outstanding

More information

The Latest Research: Hormonal Therapies

The Latest Research: Hormonal Therapies The Latest Research: Hormonal Therapies Sameer Gupta, M.D., M.P.H 9/29/2018 Attending Physician, Hematology/Oncology Bryn Mawr Hospital Clinical Assistant Professor, Jefferson Medical College Disclosures

More information

NSABP: FB-11. Shannon Puhalla, MD

NSABP: FB-11. Shannon Puhalla, MD NSABP: FB-11 Phase II Randomized Study Evaluating the Biological and Clinical Effects of the Combination of Palbociclib with Letrozole as Neoadjuvant Therapy in Post- Menopausal Women with Estrogen Receptor

More information

Breast Cancer? Breast cancer is the most common. What s New in. Janet s Case

Breast Cancer? Breast cancer is the most common. What s New in. Janet s Case Focus on CME at The University of Calgary What s New in Breast Cancer? Theresa Trotter, MD, FRCPC Breast cancer is the most common malignancy affecting women in Canada, accounting for almost a third of

More information

Multigene Testing in NCCN Breast Cancer Treatment Guidelines, v1.2011

Multigene Testing in NCCN Breast Cancer Treatment Guidelines, v1.2011 Multigene Testing in NCCN Breast Cancer Treatment Guidelines, v1.2011 Robert W. Carlson, M.D. Professor of Medicine Stanford University Chair, NCCN Breast Cancer Treatment Guidelines Panel Selection of

More information

Study Of Letrozole Extension. Coordinating Group IBCSG IBCSG BIG 1-07

Study Of Letrozole Extension. Coordinating Group IBCSG IBCSG BIG 1-07 tudy Of Letrozole Extension Coordinating Group IBCSG IBCSG 35-07 BIG 1-07 A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant

More information

Targeting CDK 4/6. Jee Hyun Kim, M.D., Ph.D. Seoul National University College of Medicine

Targeting CDK 4/6. Jee Hyun Kim, M.D., Ph.D. Seoul National University College of Medicine 2016.04.30 GBCC Education Symposium Targeting CDK 4/6 Jee Hyun Kim, M.D., Ph.D. Seoul National University College of Medicine Contents Cyclins -CDKs in cell cycle control CDK 4/6 in breast cancer Preclinical

More information

Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer Policy Number: 2.04.36 Last Review: 1/2019 Origination: 1/2006 Next Review: 9/2019 Policy

More information

Supplementary Online Content

Supplementary Online Content Supplementary Online Content Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. Published

More information

Assessment of Risk Recurrence: Adjuvant Online, OncotypeDx & Mammaprint

Assessment of Risk Recurrence: Adjuvant Online, OncotypeDx & Mammaprint Assessment of Risk Recurrence: Adjuvant Online, OncotypeDx & Mammaprint William J. Gradishar, MD Professor of Medicine Robert H. Lurie Comprehensive Cancer Center of Northwestern University Classical

More information

ASCO and San Antonio Updates

ASCO and San Antonio Updates ASCO and San Antonio Updates 30 th Annual Miami Breast Cancer Conference March 7-10, 2013 Debu Tripathy, MD Professor of Medicine University of Southern California Norris Comprehensive Cancer Center Breakthroughs

More information

TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer

TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer Marta Bonotto Department of Oncology University Hospital of Udine TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive

More information

Predicting outcome in metastatic breast cancer

Predicting outcome in metastatic breast cancer Predicting outcome in metastatic breast cancer Aleix Prat, MD, PhD Medical Oncology Department Translational Genomics and Targeted Therapeutics in Solid Tumors Monday, 15 th January, Manchester, UK Disclosures

More information

The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2 invasive breast cancer

The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2 invasive breast cancer Review Article Page 1 of 7 The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2 invasive breast cancer Vera Jean Suman 1, Matthew J. Ellis

More information

The Oncotype DX Assay A Genomic Approach to Breast Cancer

The Oncotype DX Assay A Genomic Approach to Breast Cancer The Oncotype DX Assay A Genomic Approach to Breast Cancer Pathology: 20 th and 21 st Century Size Age Phenotype Nodal status Protein/Gene Genomic Profiling Prognostic & Predictive Markers Used in Breast

More information

Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives

Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives Ian Krop Dana-Farber Cancer Institute Harvard Medical School Inchon 2018 Adjuvant Trastuzumab Improves Outcomes in HER2+ Breast

More information

Adjuvant Endocrine Therapy for Women With Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update

Adjuvant Endocrine Therapy for Women With Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update ASCO special article abstract ASSOCIATED CONTENT Appendix Data Supplement Author affiliations and support information (if applicable) appear at the end of this article. Accepted on September 17, 2018 and

More information

Optimal Treatment of Hormone Receptor Positive Disease

Optimal Treatment of Hormone Receptor Positive Disease San Francisco, CA United States January 27, 2018 San Francisco, CA USA January 27, 2018 Optimal Treatment of Hormone Receptor Positive Disease JO CHIEN, MD Associate Professor of Medicine UCSF School of

More information

Radiation and DCIS. The 16 th Annual Conference on A Multidisciplinary Approach to Comprehensive Breast Care and Imaging

Radiation and DCIS. The 16 th Annual Conference on A Multidisciplinary Approach to Comprehensive Breast Care and Imaging Radiation and DCIS The 16 th Annual Conference on A Multidisciplinary Approach to Comprehensive Breast Care and Imaging Einsley-Marie Janowski, MD, PhD Assistant Professor Department of Radiation Oncology

More information

Evolving Insights into Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology

Evolving Insights into Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology Evolving Insights into Adjuvant Chemotherapy Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology 80 70 60 50 40 30 20 10 0 EBCTCG 2005/6 Overview Control Arms with No Systemic

More information

Genomic Profiling of Tumors and Loco-Regional Recurrence

Genomic Profiling of Tumors and Loco-Regional Recurrence 1 Genomic Profiling of Tumors and Loco-Regional Recurrence Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor of Surgery,

More information

Endocrine treatment might NOT be the preferred option in Hrpos MBC. Dr. Mircea Dediu Sanador Hospital Bucharest Summer School Bucharest 2015

Endocrine treatment might NOT be the preferred option in Hrpos MBC. Dr. Mircea Dediu Sanador Hospital Bucharest Summer School Bucharest 2015 Endocrine treatment might NOT be the preferred option in Hrpos MBC Dr. Mircea Dediu Sanador Hospital Bucharest Summer School Bucharest 2015 Overall survival not improved by the AI treatment Benefit in

More information

RIBOCICLIB EN PRIMERA LINEA DE TRATAMIENTO. Dra. Elena Aguirre H.U. Miguel Servet

RIBOCICLIB EN PRIMERA LINEA DE TRATAMIENTO. Dra. Elena Aguirre H.U. Miguel Servet RIBOCICLIB EN PRIMERA LINEA DE TRATAMIENTO Dra. Elena Aguirre H.U. Miguel Servet INTRODUCTION ADVANCED BREAST CANCER HR+/HER2- YES Consider Chemo VISCERAL CRISIS? NO Endocrine Therapy X3 Toxicity Progresive

More information

Adjuvant Systemic Therapy in Early Stage Breast Cancer

Adjuvant Systemic Therapy in Early Stage Breast Cancer Adjuvant Systemic Therapy in Early Stage Breast Cancer Julie R. Gralow, M.D. Director, Breast Medical Oncology Jill Bennett Endowed Professor of Breast Cancer Professor, Global Health University of Washington

More information

Principles of breast radiation therapy

Principles of breast radiation therapy ANZ 1601/BIG 16-02 EXPERT ESMO Preceptorship Program 2017 Principles of breast radiation therapy Boon H Chua Professor Director of Cancer and Haematology Services UNSW Sydney and Prince of Wales Hospital

More information

Medical Policy An independent licensee of the Blue Cross Blue Shield Association

Medical Policy An independent licensee of the Blue Cross Blue Shield Association Assays of Genetic Expression in Tumor Tissue as a Technique Page 1 of 67 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Assays of Genetic Expression in Tumor Tissue

More information

Endocrine therapy as adjuvant or neoadjuvant therapy for breast cancer: selecting the best agents, the timing and duration of treatment

Endocrine therapy as adjuvant or neoadjuvant therapy for breast cancer: selecting the best agents, the timing and duration of treatment Review Article Page 1 of 12 Endocrine therapy as adjuvant or neoadjuvant therapy for breast cancer: selecting the best agents, the timing and duration of treatment Jun-Jie Li, Zhi-Min Shao Department of

More information

Breast Cancer Earlier Disease. Stefan Aebi Luzerner Kantonsspital

Breast Cancer Earlier Disease. Stefan Aebi Luzerner Kantonsspital Breast Cancer Earlier Disease Stefan Aebi Luzerner Kantonsspital stefan.aebi@onkologie.ch Switzerland Breast Cancer Earlier Disease Diagnosis and Prognosis Local Therapy Surgery Radiation therapy Adjuvant

More information

Is Gene Expression Profiling the Best Method for Selecting Systemic Therapy in EBC? Norman Wolmark Miami March 8, 2013

Is Gene Expression Profiling the Best Method for Selecting Systemic Therapy in EBC? Norman Wolmark Miami March 8, 2013 Is Gene Expression Profiling the Best Method for Selecting Systemic Therapy in EBC? Norman Wolmark Miami March 8, 2013 Changing Phases claudin low Lum A Lum B Basal Her2 NIH Consensus Development Panel,

More information

Current Management of Breast Cancer

Current Management of Breast Cancer Current Management of Breast Cancer F. Cardoso, MD Director, Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal ESMO Board of Directors & NR Committee Chair ESO Breast Cancer Program Coordinator

More information

ATAC Trial. 10 year median follow-up data. Approval Code: AZT-ARIM-10005

ATAC Trial. 10 year median follow-up data. Approval Code: AZT-ARIM-10005 ATAC Trial 10 year median follow-up data Approval Code: AZT-ARIM-10005 Background FDA post-approval commitment analysis to update DFS, TTR, OS and Safety Prof. Jack Cuzick on behalf of ATAC/LATTE Trialists

More information