A retrospective review of 29 Ashkenazi Jewish patients with primary fallopian tube tumors identified germline BRCA mutations in 17%. Another study of 108 women with fallopian tube cancer identified mutations in 55.6% of the Jewish women and 26.4% of non-Jewish women (30.6% overall).
Clinical Criteria and Models for Prediction of the Likelihood of a BRCA1 or BRCA2 Mutation
Several studies have assessed the frequency of BRCA1 or BRCA2 mutations in women with breast or ovarian cancer.[49,50,63,65,66,67,68,69,70,71,72,73] Personal characteristics associated with an increased likelihood of a BRCA1 and/or BRCA2 mutation include the following:
- Breast cancer diagnosed at an early age. (Some studies use age 40 years, while others use age 50 years as a cutoff.)
- Ovarian cancer.
- Bilateral breast cancer.
- A history of both breast and ovarian cancer.
- Breast cancer diagnosed in a male at any age.[65,66,67,68,71]
- Triple-negative breast cancer diagnosed in women younger than 50 years.[74,75,76]
- Ashkenazi Jewish background.[65,66,68]
Family history characteristics associated with an increased likelihood of carrying a BRCA1 and/or BRCA2 mutation include the following:
- Multiple cases of breast cancer.
- Both breast and ovarian cancer.
- One or more breast cancers in male family members.
- Ashkenazi Jewish background.[65,66,67,68]
Clinical criteria for identifying individuals who may have a BRCA1 or BRCA2 mutation
Several professional organizations, including the American Society of Clinical Oncology, the National Comprehensive Cancer Network, the American Society of Human Genetics, the American College of Medical Genetics, and the Society of Gynecologic Oncologists, have developed clinical criteria that can be helpful to health care providers in identifying individuals who may have a BRCA1 or BRCA2 mutation.
Models for prediction of the likelihood of a BRCA1 or BRCA2 mutation
Many models have been developed to predict the probability of identifying germline BRCA1/BRCA2 mutations in individuals or families. These models include those using logistic regression,[28,65,66,68,71,81,82] genetic models using Bayesian analysis (BRCAPRO and BOADICEA),[71,83] and empiric observations,[46,49,52,84,85,86] including the Myriad prevalence tables. Two of the earliest models predicted only for BRCA1 mutations and are not clinically useful at this time.[65,66] More recently, using complex segregation analysis, a polygenetic model (BOADICEA) examining both breast cancer risk and the probability of having a BRCA1 or BRCA2 mutation has been published. Even among experienced providers, the use of prediction models has been shown to increase the power to discriminate which patients are most likely to be identified as BRCA1/BRCA2 mutation carriers.[87,88] The power of several of the models has been compared in different studies, and currently there is no one model that is consistently superior to others.[89,90,91,92] Most models do not include other cancers seen in the BRCA1 and BRCA2 spectrum such as pancreatic cancer and prostate cancer. Interventions that decrease the likelihood that an individual will develop cancer (such as oophorectomy and mastectomy) may influence the ability to predict BRCA1 and BRCA2 mutation status. One study has shown that the risk models are sensitive to the amount of family history data available and do not perform as well with limited family information.