Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers: experience with a consecutive series of 111 patients using a standardized surgical-pathological protocol.

Background: Women carriers of BRCA mutations often have occult malignancy found at the time of risk-reducing bilateral salpingo-oophorectomy (RRSO). We report outcomes in 111 consecutive BRCA-positive women who had RRSO using a rigorous surgical-pathological protocol from 1996 to 2008.

Method: We identified risk factors associated with finding an occult malignancy at RRSO with outcomes followed for a median of 61 months.

Surveillance of survivors: follow-up after risk-reducing salpingo-oophorectomy in BRCA 1/2 mutation carriers.

Objectives: To characterize the post-operative care of BRCA1 and BRCA2 mutation carriers who undergo risk-reducing salpingo-oophorectomy (RRSO).

Methods: BRCA1 and BRCA2 mutation carriers from our Cancer Risk Program who elected RRSO were sent questionnaires regarding their post-surgical surveillance and treatment for menopause symptoms, primary peritoneal cancer and bone loss.

Results: In 51 mutation carriers who were surveyed a median of 6 years after RRSO, 24 (47%) received dual-energy X-ray absorptiometry (DXA) testing, yearly CA-125 serum testing and yearly pelvic examination.

Clinically applicable models to characterize BRCA1 and BRCA2 variants of uncertain significance.

Purpose: Twenty percent of individuals with a strong family and/or personal history of breast and ovarian cancer carry a deleterious mutation in BRCA1 or BRCA2. Identification of mutations in these genes is extremely beneficial for patients pursuing risk reduction strategies. Approximately 7% of individuals who have genetic testing of BRCA1 and BRCA2 carry a variant of uncertain significance (VUS), making clinical management less certain.

Lack of germ-line promoter methylation in BRCA1-negative families with familial breast cancer.

Hereditary breast cancer accounts for about 10% of breast cancer in the United States, but high-penetrance, germ-line mutations in BRCA1 and BRCA2 are responsible for less than half of these high-risk families. Epigenetic modification of DNA by promoter methylation can result in a potentially heritable epimutation that silences the gene. Using a highly sensitive technique, we assayed the BRCA1 gene for promoter methylation among 41 BRCA1- and BRCA2-negative women whose personal and family histories indicated a high risk of BRCA mutations (median prior likelihood = 60%) using the BRCAPro model.

Ductal carcinoma in situ in BRCA mutation carriers.

Purpose: The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative.

Methods: We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco.

Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation.

Context: Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort.

Objectives: To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2.

Breast tumor copy number aberration phenotypes and genomic instability.

Background: Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g.

Recruitment, genetic counseling, and BRCA testing for underserved women at a public hospital.

Genetic counseling and testing for heritable susceptibility to breast cancer caused by mutations in BRCA genes are largely unavailable to underserved women in the United States. Starting in 2002 the UCSF Cancer Risk Program offered this service free of charge to poor and medically indigent women at San Francisco General Hospital (SFGH). One recruitment strategy was a single-page questionnaire in four languages administered to women waiting for mammograms at SFGH.

A comparison of bilateral breast cancers in BRCA carriers.

Background: Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent independent events. However, the extent of concordance between the first and second tumors with respect to hormone receptor expression and other pathologic features is unknown.

Effect of Prior Bilateral Oophorectomy on the Presentation of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers.

Purpose: To compare the presentation of invasive breast cancer in BRCA1 and BRCA2 mutation carriers with and without prior bilateral oophorectomy.

Patients And Methods: Women with a BRCA1 or BRCA2 mutation with the diagnosis of invasive breast cancer were identified from ten cancer genetics clinics. The medical history, medical treatment records and pathology reports for the breast cancers were reviewed.

Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy.

Purpose: Women who carry deleterious mutations of BRCA1 or BRCA2 genes have up to a 54% lifetime risk of developing ovarian cancer. After childbearing, women at high risk increasingly choose bilateral risk-reducing salpingo-oophorectomy (RRSO). Two recent studies of BRCA mutation carriers reported occult malignancy in 2.

The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers.

Objective: To estimate the risk of ovarian cancer after a primary diagnosis of breast cancer among women with a BRCA1 or BRCA2 mutation and to identify host and treatment-related factors that might modify the risk.

Patients And Methods: Patients were 491 women with stage I or stage II breast cancer, diagnosed from 1975 to 2000 and for whom a BRCA1 or BRCA2 mutation had been identified. Patients were followed from the initial diagnosis of breast cancer until either ovarian cancer, prophylactic oophorectomy, death, or 2002.

Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

Purpose: To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer.

Patients And Methods: Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type.

Purpose: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied.

Experimental Design: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America.

Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1-related breast carcinoma.

Background: A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas.