Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis

Abstract

Background: To prospectively assess the efficacy of bilateral risk-reducing mastectomy (BRRM) when compared with surveillance on breast cancer (BC) risk and mortality in healthy BRCA1 and BRCA2 mutation carriers.Patients and methods: Five hundred and seventy healthy female mutation carriers (405 BRCA1, 165 BRCA2) were selected from the institutional Family Cancer Clinic database. Eventually, 156 BRCA1 and 56 BRCA2 mutation carriers underwent BRRM. The effect of BRRM versus surveillance was estimated using Cox models.Results: During 2037 person-years of observation (PYO), 57 BC cases occurred in the surveillance group versus zero cases during 1379 PYO in the BRRM group (incidence rates, 28 and 0 per 1000 PYO, respectively). In the surveillance group, four women died of BC, while one woman in the BRRM group presented with metastatic BC 3.5 years after BRRM (no primary BC), and died afterward, yielding a HR of 0.29 (95% CI 0.02-2.61) for BC-specific mortality. Conclusions:In healthy BRCA1/2 mutation carriers, BRRM when compared with surveillance reduces BC risk substantially, while longer follow-up is warranted to confirm survival benefits.

Intensified Surveillance for Early Detection of Breast Cancer in High-Risk Patients

“…Based on model calculations, it is estimated that without intervention, 47% of BRCA1 mutation carriers und 29% of BRCA2 mutation carriers will die before reaching age 70, compared to 16% in the general US population [71]. In this situation, offering early detection measures for secondary prevention to high-risk women means taking on a large responsibility, especially as effective surgical prevention measures such as bilateral risk-reducing mastectomy and/or salpingo-oophorectomy are available [72,73]. Unfortunately, very few reliable data are available regarding the effectiveness of intensified surveillance in high-risk women in regards to reducing breast cancer mortality [6,22,74].…”

“…However, intensified surveillance appears to be somewhat less effective in BRCA1 mutation carriers [6], in whom more advanced stage cancers, symptomatic interval cancers as well as breast cancer deaths have been observed despite regular screening with MRI in several of the high-risk surveillance observational studies [61,66,73,78,79]. In the analysis of Heijnsdijk et al [61], which combined data from the Dutch, Canadian and UK high-risk screening trials, the share of T1c and T2+ tumors was 29% and 22%, respectively, for BRCA1 mutation carriers, compared to 16% and 4% for BRCA2 mutation carriers.…”

Media Exposure and Genetic Literacy Skills to Evaluate Angelina Jolie's Decision for Prophylactic Mastectomy

“…Several studies have shown both mastectomies and oophorectomies to be effective in cancer risk reduction, though the relative benefit of mastectomy compared to less invasive methods (i.e. intensive screening, chemoprevention) remains uncertain and long-term survival benefits need confirmation [11,12,13]. As these elective surgeries come with significant risk, financial cost, and personal sacrifice, they are not universally recommended by the United States Preventive Services Task Force (USPSTF) or the National Comprehensive Cancer Network.…”

Análise de custo-efetividade de programa para diagnóstico de mutação germinativa em genes BRCA1/2 e de estratégias preventivas para pacientes com câncer de ovário e seus familiares de primeiro grau

“…Estudos prospectivos que apresentam risco relativo para neoplasias malignas de mama e ovário após a realização de salpingo-ooforectomia redutora de risco (45,(127)(128)(129)(130) . .. Estudos prospectivos que apresentam risco relativo para câncer de mama após a realização de mastectomia bilateral profilática (45,(131)(132)(133) . (31,32,(136)(137)(138) .…”

“…Estudos prospectivos que apresentam risco relativo para câncer de mama após a realização de mastectomia bilateral profilática (45,(131)(132)(133) . (17,43,44,131,(134)(135)(136) .…”