BackgroundApproximately 8–15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer.MethodsIn a cross sectional study performed in one reference centre for cancer treatment in São Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA).ResultsNineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1–2 deleted and exon 5–7 deleted) were identified. Three mutations were detected more than once (c.3331_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961_962delTG) and one in BRCA2 (c.1963_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c.5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A).ConclusionsAmong epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost ¾ of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2966-x) contains supplementary material, which is available to authorized users.

The age at diagnosis of breast cancer in non-carriers in BRCA mutation families is younger than expected, yielding an increased risk in the fifth decade. This effect is most evident in BRCA1 families. If our results are confirmed by others, this could affect the advice given on breast cancer screening to proven non-carriers between the age of 40 and 50 in such families.

Background Oophorectomy is recommended for women at increased risk for ovarian cancer. When performed at premenopausal age oophorectomy induces acute surgical menopause, with unwanted consequences. Objective To investigate bone mineral density (BMD) and fracture prevalence after surgical menopause. Search strategy A literature search of PubMed, EMBASE and Cochrane library was performed with no date restriction. Date of last search was March 1st, 2016. Selection criteria Primary studies reporting on BMD, T‐scores or fracture prevalence in women with surgical menopause and age‐matched control groups. Data collection and analysis Data were extracted on BMD (g/cm2), T‐scores and fracture prevalence in women with surgical menopause and control groups. Quality was assessed by an adaptation of the Downs and Black checklist. Random effects models were used to meta‐analyse results of studies reporting on BMD or fracture rates. Main results Seventeen studies were included, comprising 43 386 women with surgical menopause. Ten studies provided sufficient data for meta‐analysis. BMD after surgical menopause was significantly lower than in premenopausal age‐matched women [mean difference lumbar spine, −0.15 g/cm2 (95% CI, −0.19 to −0.11 g/cm2); femoral neck, −0.17 g/cm2 (95% CI, −0.23 to −0.11 g/cm2)] but not lower than in women with natural menopause [lumbar spine, −0.02 g/cm2 (95% CI, −0.04 to 0.00 g/cm2); femoral neck, 0.04 g/cm2 (95% CI, −0.09 to 0.16 g/cm2)]. Hip fracture rate was not higher after surgical menopause compared with natural menopause [hazard ratio: 0.85 (95% CI, 0.70 to 1.04)]. Author's conclusions No evident effect of surgical menopause was observed on BMD and fracture prevalence compared with natural menopause. However, available studies are prone to bias and need to be interpreted with caution. Tweetable abstract Bone health after menopause: no evidence for additional effect of surgical menopause on BMD and fractures.