Outcome of risk-reducing salpingo-oophorectomy in BRCA carriers and women of unknown mutation status

Abstract

Objective To compare surgical outcomes and occult cancer rates at risk-reducing salpingo-oophorectomy in BRCA carriers and high-risk women who had not undergone genetic testing.Design Prospective cohort study.Setting Tertiary high-risk familial gynaecological cancer clinic.Population Women undergoing risk-reducing salpingooophorectomy between January 2005 and November 2009.Methods Women at high-risk of ovarian/tubal cancer were identified on the basis of the inclusion criteria for the UK Familial Ovarian Cancer Screening Study. Risk management options discussed with 1456 high-risk women included risk-reducing salpingo-oophorectomy. A strict histopathological protocol with serial slicing was used to assess tubes and ovaries.Results In total, 308 high-risk women (191 with unknown mutation status; 117 known BRCA1/BRCA2 carriers) chose risk-reducing surgery; 94.5% of procedures were performed laparoscopically. The surgical complication rate was 3.9% (95% CI 2.0-6.7). Four ovarian and ten tubal occult invasive/in situ cancers were found. The overall occult invasive cancer rate was 5.1% (95% CI 1.9-10.83) in BRCA1/BRCA2 carriers and 1.05% (95% CI 0.13-3.73) in untested women. When tubal in situ cancers were included, the overall rate was 4.55% (95% CI 2.5-7.5). Two untested women with tubal carcinoma in situ were subsequently found to be BRCA carriers. The median ages of BRCA carriers (58 years; IQR 13.4 years) and untested women (49.5 years; IQR 20.6 years) with occult invasive/in situ cancer were not significantly different (P = 0.454).Conclusions Both high-risk women of unknown mutation status and BRCA carriers have a significant (although higher in the latter group) rate of occult invasive/in situ tubal/ovarian cancer, with a similar age distribution at detection. The data has important implications for counselling high-risk women on the likelihood of occult malignancy and perioperative complications at riskreducing salpingo-oophorectomy. Women with occult disease should be offered genetic testing.

A novel outlook on preventive tubectomy

“…Согласно этой точке зрения, как высокодифференциро-ванные, так и низкодифференцированные серозные кар-циномы имеют в итоге происхождение из маточной тру-бы. Следует отметить, что даже микроскопические по-вреждения могут распространять злокачественные клетки по брюшной полости, что было подтверждено смывами из брюшной полости в группе пациенток с наличием карци-номы только маточных труб [26]. Таким образом, тради-ционное представление, что поражения серозной карци-номой брюшины, сальника и других внутрибрюшных ор-ганов первоначально исходят из яичника, подвергается сомнению.…”

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

“…A recomendação atual para o manejo de risco em mulheres portadoras de mutação nos genes BRCA1 e BRCA2 consiste em salpingo-ooforectomia bilateral entre os 35 e 40 anos de idade, após a constituição da prole (10,16) . A cirurgia é recomendada por reduzir o risco de câncer de ovário em 80 a 95% e o de mama na pré-menopausa em 50%.…”

“…A cirurgia é recomendada por reduzir o risco de câncer de ovário em 80 a 95% e o de mama na pré-menopausa em 50%. Após a realização do procedimento, ainda reside um risco residual de 4,3% para o desenvolvimento de câncer peritoneal primário num curso de 20 anos (10,16) .…”

“…Um estudo avaliando pacientes submetidas a ooforectomia identificou tumores ocultos em 5,1% dos casos. A maior parte destes eventos ocorreu em tubas uterinas, suportando a hipótese de que o câncer de ovário em portadores de mutação em genes BRCA1/2 pode originar-se em tubas e epitélio extrauterino mulleriano (16) .…”

“…A salpingo-ooforectomia redutora de risco é recomendada por reduzir o risco de câncer de ovário em 80 a 95% e do câncer de mama na pré-menopausa, em até 50%. (16) . A realização de mastectomia bilateral profilática está associada a uma redução da ordem de 95% no risco para o câncer de mama (17) .…”