Prophylactic Mastectomy State of the Art
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1 Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY th Brazilian Breast Cancer Conference Sao Paulo, Brazil 9 March 2012 Prophylactic Mastectomy State of the Art Monica Morrow MD Chief, Breast Surgery Service Anne Burnett Windfohr Chair of Clinical Oncology Memorial Sloan-Kettering Cancer Center
2 Prophylactic Mastectomy: Who and How Bilateral PM Selection Efficacy CPM Selection Surgical Technique SN biopsy
3 When Should PM Be Considered? Magnitude of Known Risk Factors Relative Risk < > 4 Early menarche Family hx 1 o BRCA mutation relative Late menopause > 35 first birth Radiation exposure Nulliparity Dense breasts LCIS Obesity Atypical hyperplasia Alcohol HRT
4 BRCA Mutations:. Risk of Breast/Ovarian Cancer by Age Percent In ncrease J Natl Cancer Inst 2010;102:755
5 Risk of Breast Cancer After RT for Hodgkin s Lymphoma Age at Diagnosis Age at Diagnosis Relative Risk No increase
6 Absolute Risk of Cancer After LCIS Diagnosis Study F/u Ipsilateral CA Contralateral CA 7 studies (74-93) n = 610 Fisher 2004 n = yrs (5-24) 12% (74/602) 12 yrs 9% 16/180 9% 37/610 8% 14/180 Fisher ER, Cancer 2004;100:238-44
7 How Effective Is PM? Moderate Risk High Risk O E % Reduction O E % Reduction Incidence Death Hartmann LC, N Engl J Med 1999;340:77-84
8 How Effective Is PM in BRCA Mutation Carriers? Study PROSE Meijers-Heijboer Follow-up 6.4 yrs 3.0 yrs PM 1.9% (2/105) 0 (76) No PM 48.7% (184/378) 12.7% (8/63) HR 0.05; 95% CI, p = Rebbeck T, J Clin Oncol 2004;22:1055 Meijers-Heijboer H, NEJM 2001;345:159
9 Metaanalysis of Risk-Reducing Estimates Associated with RRSO Ovarian ca Breast ca Breast ca BRCA 1 Breast ca BRCA 2 Rebbeck T, JNCI 2009;101:80
10 Acceptability of Prophylactic Surgery % Accepting Author Group PM PO Wagner Austrian BRCA 1/2 carriers Lehrman Unaffected U.S. carries Meijers-Heijboer Unaffected Dutch carriers Eisinger French women attending cancer genetics clinics 4 16
11 BRCA1 Management by Specialty Dhar SO, Br Ca Res Treat 2011;129:221
12 Contralateral Prophylactic Mastectomy Rates Among All Patients Undergoing Mastectomy Invasive Cancer Tuttle TM, JCO 2007;25:5203
13 Contralateral Prophylactic Mastectomy Rates Among All Patients Undergoing Mastectomy DCIS Tuttle TM. JCO ;9:1365
14 Who Gets CPM? Patient Younger White Insured Family Hx BRCA testing (regardless of result) Tumor Lobular cancer DCIS Treatment Reconstruction MRI Yi M, Cancer Prev Res 2010;3:1026 Stucky CC, Ann Surg Oncol 2010;17(Suppl 3):330 Yao K, Ann Surg Oncol 2010;17:2554 King TA, JCO 2011;29(16):2158
15 Why Is CPM Performed? High Risk of Contralateral Cancer Improve Survival Optimize Cosmetic Outcome of Reconstruction
16 Risk of Contralateral Cancer in BRCA Mutation Carriers Proportion Rela apse Free (%) Contralateral Breast Log-rank p = Years Since Diagnosis Haffty, et al. Lancet, 2002
17 Effect of Age on Contralateral Cancer in BRCA 1 Carriers Verhoog LC, Br J Cancer 2000;83:384
18 Impact of Tamoxifen or Oophorectomy. on CBC Risk in BRCA Carriers Either (n = 159) Neither (n = 151) Metcalfe K, JCO 2004;22:2328
19 Contralateral Cancer After RT for Hodgkins Lymphoma Sporadic BC n = 741 HL Survivors n = 253 Elkin E, JCO 2011;29(18):2466
20 What Is the Risk of Contralateral Cancer? SEER ,501 unilateral DCIS, Stage I+II cancer 4.2% incidence contralateral ca 10-year actuarial risk: 6.1% 20-year actuarial risk: 12.0% Gao X, IJROBP 2003;56:1038
21 What Is the Risk of Contralateral Cancer? Time (years) p-value Histology DCIS Ductal Lobular Medullary
22 How Does Treatment Modify Risk? 50% - 60% by endocrine rx 20% by chemotherapy By trastuzumab Older studies prior to widespread use of adjuvant therapy overestimate risk
23 Incidence of Contralateral Cancer Nichols H, JCO 2011;29(12):1564
24 Annual Incidence of Contralateral Breast Cancer Per 100/yr Age First Diagnosis ER Positive ER Negative Nichols H, JCO 2011;29(12):1564
25 Do Increasing Rates of CPM Reflect Greater Awareness of Breast Cancer Risk? MSKCC Experience n = 2965 Unilateral breast cancer Stage 0-III Jan 1997 Dec 2005 CPM 12 months of dx King TA, JCO 2011;29(16):2158
26 Results CPM Rate by Year of Surgery 7% n = % CPM Ra ate Year of Treatment King TA, JCO 2011;29(16):2158
27 Contralateral Prophylactic Mastectomy High Risk Population (n = 407) BRCA mutation carriers = 37 Prior mantle radiation = (13%) patients having CPM King TA, JCO 2011;29(16):2158
28 Contralateral Prophylactic Mastectomy Patient Characteristics No-CPM (n=2558) CPM (n=407) p-value Age at surgery Mean 54.7 yrs 45.6 yrs <.0001 Race NonWhite 628 (25%) 29(7%) <.0001 White 1912(75%) 378(93%) Family History No 1525(60%) 127(32%) <.0001 Yes 1010(40%) 276(68%) King T, JCO ;29:
29 Contralateral Prophylactic Mastectomy Familial Risk Factors No-CPM (n=2558) CPM (n=407) p-value Number of FDR w/ BC 0 558(55%) 118(43%) (39%) 135(49%) 2 or more 59(6%) 23(8%) Genetic testing Yes 243(10%) 118(29%) <.0001 Mutation Carrier Yes 30(12%) 37(31%) <.0001 King T, JCO ;29:
30 Contralateral Prophylactic Mastectomy Clinical Management Factors No-CPM (n=2558) CPM (n=407) p-value MRI at cancer diagnosis Yes 413(16%) 174(43%) <.0001 Additional biopsy due to MRI Yes 252(61%) 108(62%) NS Ipsilateral 235(57%) 58(33%) Contralateral/Bilateral 17(4%) 50(29%) <.0001 King T, JCO ;29:
31 Contralateral Prophylactic Mastectomy Clinical Management Factors No-CPM (n=2558) CPM (n=407) p-value Attempted BCS Yes 421(16%) 112(28%) <.0001 Breast Reconstruction Yes 1306(51%) 354(87%) <.0001 King T, JCO ;29:
32 Predictors of CPM Multivariate Random-Effects Logistic Regression OR p-value Age 50 vs age < <.0001 Race (Other vs White) <.0001 Family hx of Breast Cancer <.0001 DCIS only vs IFDC IFLC vs IFDC MRI at DX <.0001 BCT Attempted Adjusted for surgeon King T, JCO ;29:
33 Does CPM Improve Survival? Cochrane Review yr Overall Survival Disease-Specific Survival 4 studies, 246 patients 6 studies CPM No CPM Heterogenous results Lack of adjustment for n = 64 n = 182 differences in prognostic 64% 48% factors P =.26 Conclusions: Methodologic limitations. Little good data to indicate CPM will improve survival Lostumbo L. Cochrane Collaboration 2010
34 Is CPM Likely to Increase Survival? SEER ,106 unilateral ductal cancers CPM in 8.3% n = 8902 Bedrosian I, JNCI 2010;102:401
35 Rates of CBC Age < 50, Stage I, II ER+ ER- p-value No CPM 0.46% 0.90% <.001 CPM 0.13% 0.16%.90 p Median follow-up 47 months Bedrosian I, JNCI 2010;102:401
36 CPM and Survival ER+ ER- Adjusted surviv val function (%) Adjusted surviv val function (%) CPM No CPM CPM No CPM Years after diagnosis Years after diagnosis * Adjusted analysis Bedrosian I, JNCI 2010;102:401
37 CPM and Survival No benefit in ER+ patients No benefit in ER- 60 years Survival difference in ER- < 50 much greater than expected for < 1% difference in incidence. Bedrosian I, JNCI 2010;102:401
38 Patient Satisfaction Unilateral vs Bilateral Mastectomy Single institution survey of all reconstruction patients Jan 1999-Dec 2006 Response rate 75% Minimum 13 months follow-up, mean 49 months Craft RO, PRS 2011
39 Outcome Unilateral vs Bilateral Mastectomy + Recon Unilateral Bilateral P-value # Patients General satisfaction 66.8% 66.9% 0.99 Aesthetic satisfaction 64.8% 62.6% 0.65 Mean # addl. surgeries Total complications 34.6% 34.1% 0.93 Craft RO, PRS 2011
40 Technique of PM Same anatomic limits, flap thickness as therapeutic mastectomy Skin sparing routine
41
42 Sentinel Node Bx in PM Metaanalysis: 6 studies, 1343 PM Invasive ca: 1.7% 95% CI Positive SN: 1.9% 95% CI MSKCC Experience: 625 CPM Invasive ca: 5 (0.8%) Positive SN: 1 (0.2%) Zhou WB, Can J Surg 2011;54:300 King TA, Ann Surg 2011; 254:2-7
43 Sentinel Node Bx in PM Not routine incidence of side effects exceeds benefit. Older studies overestimate incidence of nodal metastases due to inclusion of isolated tumor cells, micrometastases. Reserve for patients with unsampled imaging abnormalities or core bx of atypia where risk of cancer is increased.
44 When Is CPM Indicated? Unilateral cancer and BRCA 1/2 mutation carrier Hx mantle irradiation Hodgkins lymphoma Physician-initiated discussion
45 When Is CPM Indicated? Unlikely to benefit Poor prognosis from current cancer Node positive, large primary, triple negative Effective risk-reducing therapy for current cancer ER, PR positive, will get endocrine rx? HER2 positive, will get trastuzumab
46 When Is CPM Indicated? MD-initiated discussion rarely appropriate outside setting of known/suspected mutation carrier. May be appropriate if patient-initiated AND: Young age DCIS/favorable prognosis invasive ca Significant family Hx Breasts difficult to monitor: dense, multiple bx
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