San Antonio Breast Cancer Symposium Highlights A Surgeon s Perspective
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1 San Antonio Breast Cancer Symposium Highlights 2016 A Surgeon s Perspective Candice Sauder M.D., M.Ed. Department of Surgery Division of Surgical Oncology UC Davis Overview Genetic Risk and Guidelines S2-01 ASBS Consensus Guideline on Hereditary Genetic Testing Genetic Risk and Breast Cancer Outcomes S2-03 Ductal Carcinoma In Situ SSS-ASTRO-ASCO DCIS Margin Guidelines S5-01 P S2-07 P OT Alliance
2 Genetic Risk and Guidelines Last 4 years drastic changes in the field of cancer genetics Particularly this field now contains genetic panels that can have up to 50 genes What genes were included? Known to drive breast cancer risk vs. minimal information but a possibility of involvement How do we handle giving a clinical risk estimate with the wide conference intervals seen on many of these genes? What does a VUS mean for our patients? Genetic Risk and Guidelines Fergus Crouch in S2-01 summarizing Doug Eastman et al. NEJM
3 Genetic Risk and Guidelines Breast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 60,000 breast cancer patients Couch FJ, Hu C, Lilyquist J, Shimelis H, Akinhanmi M, Na J, Polley EC, Hart SN, McFarland R, LaDuca H, Huether R, Goldgar DE, Dolinsky JS (S2-01) 121,197 patients examined from the Ambry Genetics database from March 2012-June % female 65% Caucasian Mutations were detected in 9% of patients 12 genes showed a significant association with breast cancer Genetic Risk and Guidelines High Risk Moderate Risk Low Risk BRCA1 BRCA2 TP53 PTEN CDH1 PALB2 ATM CHEK2 RAD51D NF1 BARD1 MSH6 BRIP1 RAD50 RAD51c MRE11A NBN 3
4 Genetic Risk and Guidelines ASBS Consensus Guidelines on Hereditary Genetic Testing BRCA1 Breast cancer (up to 67%) Contralateral br cancer (up to 30%) Ovarian cancer (up to 45%) Annual breast MRI (start age 25) Annual mammogram (start age 30) Risk-reducing bilateral mastectomy BRCA2 Breast cancer (up to 66%) Contralateral br cancer (up to 30%) Ovarian cancer (up to 12%) Male breast cancer Prostate cancer TP53 Breast cancer Soft tissue sarcomas Osteosarcomas Brain tumors Adrenocortical carcinoma Multiple primary tumors Annual breast MRI (start age 25) Annual mammogram (start age 30) Chemoprevention Risk-reducing bilateral mastectomy Annual breast MRI (start age 20) Annual mammogram (start age 30) Risk-reducing bilateral mastectomy Genetic Risk and Guidelines ASBS Consensus Guidelines on Hereditary Genetic Testing PALB2 Breast cancer (33%, but 58% with 2 first-degree relatives) Pancreatic cancer Male breast CDH1 PTEN ATM Breast cancer (39% of lobular carcinoma) Gastric cancer Colorectal cancer Breast cancer Thyroid cancer Endometrial cancer Colorectal cancer Kidney cancer Breast cancer (rare mutations with a 40-60%) Annual breast MRI (start age 25) Annual mammogram (start age 30) Risk-reducing bilateral mastectomy Annual breast MRI (start age 30) Annual mammogram (start age 30) Risk-reducing bilateral mastectomy Gastric screening Annual breast MRI (start age 30) Annual mammogram (start age 30) Risk-reducing bilateral mastectomy Management recommendations have not been established 4
5 Genetic Risk and Guidelines CHEK2 STK-11 BRIP 1 ASBS Consensus Guidelines on Hereditary Genetic Testing Breast cancer (20% but increases with 44% with 1st- & 2nd-degree relatives) 30% risk of contralateral breast cancer Male breast cancer Colon cancer Prostate cancer Thyroid cancer Kidney cancer Breast cancer Ovarian cancer Colorectal cancer Duodenal cancer Pancreatic cancer Breast cancer (2- to 3.5-fold) Ovarian cancer (8-fold) MRI Chemoprevention Risk-reducing bilateral mastectomy Annual breast MRI (start age 30) Annual mammogram (start age 30) MRI Chemoprevention Consider BSO Genetic Risk & Breast Cancer Outcomes Does BRCA status affect outcome in young breast cancer patients? Results from the prospective study of outcomes in sporadic and hereditary breast cancer (POSH) Eccles DM, Copson ER, Maishman T, Tapper W, Cutress R, Gerty S, Stanton L, Altman DG, Durcan L, Simmonds P, Decker B, Allen J, Luccarini C, Easton D, Dunning A (S2-03) 3053 patients examined from the UK All had Invasive Breast Cancer 40 years old Blood samples were tested for BRCA1 & 2 in 2016 Mutations were found in 379/2759 (~14%) 5
6 Genetic Risk & Breast Cancer Outcomes Looked at the molecular subgroups TNBC survival favored BRCA gene carriers (~11% at 10 years) Ductal Carcinoma In Situ Society of Surgical Oncology American Society for Radiation Oncology American Society of Clinical Oncology Consensus Guideline on Margins for Breast- Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ Monica Morrow, Kimberly J. Van Zee, Lawrence J. Solin, Nehmat Houssami, Mariana Chavez-MacGregor, Jay R. Harris, Janet Horton, Shelley Hwang, Peggy L. Johnson, M. Luke Marinovich, Stuart J. Schnitt, Irene Wapnir, and Meena S. Moran Literature review which included 20 studies of 7883 women 2mm margins were adequate Larger margins did not decrease the RR Positive margins have a much higher RR 6
7 Ductal Carcinoma In Situ Treatment with surgery alone is linked to a higher RR compared to treatment with surgery and WBRT. Treatment with HT can reduce the RR, but no data has shown a link between HT and the width of clean margins. The width of the clean margins shouldn t affect the type of WBRT a woman receives. DCIS with microinvasion should be considered DCIS when deciding on optimal margin width. Ductal Carcinoma In Situ DCIS biological risk profile predicts risk of recurrence after breast conserving surgery in a Kaiser Permanente NW population Bremer T, Whitworth P, Leo M, Barry T, Goldstein N, Ganders C, Francisco M, Leesman G, Linke S, Patel R, Pellicane J, Weinmann S. (S5-01) Validation study of a new prognostic indicator 0-10 (Low 3, High >3) Goal to identify the 72% that are not helped by RT Correa et al. Natl Cancer Inst Monographs
8 Ductal Carcinoma In Situ DCIS BCS ( ) N=608 Prospective Biological Risk Signature Testing N=455 RT N=377 No RT N=78 10 year IBE Risk Ductal Carcinoma In Situ 8
9 Ductal Carcinoma In Situ Rates of ipsilateral breast tumor recurrence (IBTR) following breast concerving surgery (BCS) and hypofractionated radiotherapy for ductal carcinoma in situ (DCIS) Dumitru D, Benson J, Wishart G, Provenzano E. (P ) 15 fractions for 40Gy Ductal Carcinoma In Situ 8.3% developed recurrence (n=9 with RT and n=5 no RT, p=0.534) at 10.5 years Similar IBTR rates seen in with Traditional WBRT (approx. 1% per year) 9
10 Degree of pathologic response after NCT correlates with both DFS and OS in both the breast and axilla Likelihood of pcr is predicted by molecular subtype Total ~40% ER/PR % Her % Triple Negative 49.4% Boughey JC et al. Ann Surg Dominici et al. Cancer Bear et al. JCO Overall pcr is a prognostic factor, which differs slightly by molecular subtype Predictors of locoregional recurrence after neoadjuvant chemotherapy and surgery for node positive breast cancer: Results from ACOSOG Z1071 (Alliance) Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Hunt KK (P ) 5 year LRR 10
11 Clinically Negative Axilla NCT SLNB Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort Classe J-M, Loaec C, Alran S, Paillocher N, Tunon-Lara C, Gimbergues P, Faure-Virelizier C, Chauvet M-P, Lasry S, Dupre P-F, Verhaeghe J-L, De Blaye P, Gutowski M, Barranger E, Lecuru F, Lefevre Lacoeuille C, Loussert L, Lambaudie E, Ferron G (S2-07) Useful, feasible, safe 92.4% female 65% Caucasian Cohort of 15 Institutions 11
12 T1-4 Br Ca Ax Ultrasound N=608 +LN SLNB + ALND n= % identified FNR ~20% - LN SLNB ± ALND n=509 97% identified + SLN 24% N=139 - SLN 75% ALND N=14 ALND pn-= 73% (n=88) pn+= 24% (Mi=12Macro= 15) SLNB alone N=418 3 year survival N=418 Overall Survival 97.8% Disease Free Survival 94.8% Recurrence N=10 Metastasis 3 Ipsilateral Breast 3 Contralateral Breast 3 Lymph Node 1 12
13 Clinically Negative Axilla NCT SLNB Clinically Positive Axilla NCT Complete Response? No Complete Response ALND Predictor of LRR after NCT in NSABP B-18 & B-27 cn+/ypn+ cn-/ypn+ cn+/ypn- cn-/ypn- E. Mamounas. JCO
14 ACOSOG (Alliance) z1071 Trial T1-4, N1-2, M0 With Bx proven LN disease N=663 NCT SLN IDed ( 2), then followed with ALND N=525 (79%) FNR 12.6% Goal 10% J. Boughey et al. JAMA ACOSOG (Alliance) z1071 Trial Number of SLN Removed False Negative Rate 32% 21.1% 9.1% Total 12.6% J. Boughey et al. JAMA
15 Targeted Axillary Lymph Node Dissection (TAD) Node +LN Total LN FNR Clipped % SLNB % SLNB + Clipped % A Caudle et al. JCO Normal Exam after chemotherapy axillary imaging Remove 3LNs Dual Mapping Remove Targeted/Clipped Node Count all remaining disease as a positive node Even IHC detected (FNR 8.4%) 15
16 NSABP B-51/RTOG 1304 (NRG 9353) Poster OT Alliance for Clinical Trials in Oncology A11202 King, T. A. & Morrow, M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat. Rev. Clin. Oncol
17 Thank You. 17
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