Breast and ovarian cancer penetrance of BRCA1/2 mutations among Hong Kong women

Abstract

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are associated with increased risk of breast and ovarian cancer. The penetrance of breast and ovarian cancer in BRCA1/2 mutation carriers has been well characterized in Caucasian but not in Asian. Two studies have investigated the breast cancer risk in Asian women with BRCA1/2 mutations, and no published estimates are available for ovarian cancer. Therefore, we estimated the age-specific cumulative risk of BRCA1/2-associated breast and ovarian cancer in Chinese women. From Jan 2007 to Nov 2015, the Hong Kong Hereditary Breast Cancer Family Registry identified 1635 families with hereditary breast-ovarian cancer. Among probands in these families, 66 had BRCA1 mutations, 84 had BRCA2 mutations, and 1,485 tested negative for BRCA1/2 mutations. Using the female first-degree relatives of these probands, we estimated the risk of breast and ovarian cancer using a modified marginal likelihood approach. Estimates of breast cancer penetrance by age 70 were 53.7% (95% CI 34.5-71.6%) for BRCA1 mutation carriers and 48.3% (95% CI 31.8-68.5%) for BRCA2. The estimated risk of ovarian cancer by age 70 was 21.5% and 7.3% for Chinese women carrying BRCA1 or BRCA2 mutation respectively. A meta-analysis of available studies in Asian women revealed pooled estimates of breast cancer risk by age 70 of 44.8% (95% CI 33-57.2%) and 40.7% (95% CI 31.3-50.9%) for BRCA1 and BRCA2 mutation carriers respectively. These data suggest that BRCA1/2-associated breast cancer risk for Chinese women is similar to that for Caucasian women, although BRCA1/2-associated ovarian cancer risks are lower for Chinese women.

Impact of BRCA Mutation on the Survival and Risk of Contralateral Breast Cancer in Asian Breast Cancer Patients

“…Women with germline BRCA mutations have extremely high lifetime risks of developing breast and ovarian cancers [4][5][6][7]. Previous studies have shown that the cumulative incidence of breast cancer for BRCA1 and BRCA2-mutation carriers by 80 years old was about 72% [con dence interval (CI) 65% -79%] and 69% (61% -77%), respectively [7]. More speci cally, reports from Asian BRCA studies revealed that BRCA1 and BRCA2 mutation carriers have a 49-54% and 35-48% chance of developing breast cancer, respectively [6,7].…”

“…Previous studies have shown that the cumulative incidence of breast cancer for BRCA1 and BRCA2-mutation carriers by 80 years old was about 72% [con dence interval (CI) 65% -79%] and 69% (61% -77%), respectively [7]. More speci cally, reports from Asian BRCA studies revealed that BRCA1 and BRCA2 mutation carriers have a 49-54% and 35-48% chance of developing breast cancer, respectively [6,7]. The risk of recurrent or contralateral breast cancer (CBC) also signi cantly increases in BRCA mutation carriers compared to non-BRCA carrier patients [4,[8][9][10].…”

α-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells

“…With some congruence, breast and gynecological cancers, especially ovarian cancer, have been reported to be related to each other owing to their similar genetic basis (27), while a patient with breast cancer was later found to have primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus (28). Indeed, an increased risk of breast and ovarian cancers has been reported to be associated with germline mutations in BRCA1 and BRCA2 (29). This led us to investigate the role of α-mangostin in SKOV-3 ovarian cancer cells.…”

Cáncer de ovario

“…En las familias con un historial de cáncer de ovario o de mama, las mutaciones BRCA son responsables de aproximadamente el 90% de los casos de cáncer de ovario. El riesgo estimado de cáncer de ovario es del 39% en los portadores de mutaciones BRCA1 y del 17% en los portadores de mutaciones BRCA2 (8).…”

“…Las pacientes deben someterse a un examen físico completo, incluido un examen recto vaginal con la vejiga vacía para evaluar las masas pélvicas y abdominales. En el examen recto vaginal, se debe evaluar los signos de disfunción endocrina, síndromes para neoplásicos y enfermedad metastática, incluyendo linfadenopatía inguinal (7,8).…”