She said that “375 BRCA variants whose significance was uncertain a year ago have now been classified for cancer risk (as either benign/likely benign or pathogenic/likely pathogenic) as a result of this novel data share initiative. An individual who may have received a test report indicating 1 of these variants a year ago may not have been able to make the most well-informed decisions. We at Quest Diagnostics believe this heightened clarity is a significant step forward for BRCA patient testing.”

Dr Beroud pointed out that “if a variant’s classification changes due to advances in knowledge, laboratory members of BRCA Share will be notified and may use the new data to inform decisions about prior patient test results.”

Although breast and ovarian cancers are associated primarily with BRCA1 and BRCA2 mutations, highly penetrant genes also associated with hereditary breast cancer include PALB2, TP53, PTEN, STK11, and CDH1 and, with ovarian cancer, BARD1, BRIP1, CHEK2, MRE11A, NBN, PALB2, RAD50, RAD51C, RAD51D and TP53. Mutations in the mismatch repair genes that lead to Lynch syndrome—MLH1, MSH2, MSH6, PMS2, and EPCAM—can increase lifetime ovarian cancer risk by 10% to 12%.

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Since the disease and treatment implications of many of these genes are not entirely understood, the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend that multi-gene testing be offered only in the context of professional genetic expertise, which includes counseling before and after the test.2,3

One of the most important aspects of such counseling is to create an individualized cancer risk management plan for each patient. This plan should include only “identified gene mutations that are clinically actionable,” according to the NCCN guidelines. This is especially critical if recommended risk reduction might include bilateral mastectomy or salpingo-oophorectomy.

Before securing informed consent to genetic testing, however, “it is necessary to have some basic understanding of heredity, types of test results, pros/cons, insurance implications, and potential health implications,” Dr Pal said. When individuals are tested for multiple genes simultaneously, “we explain that there are 3 types of test results: positive, negative, and VUS,” and “that VUS test results are more common with more genes tested.”

We need “more awareness about options for testing in minority populations that should be addressed at the patient, provider, and system level.” While most referred patients do undergo testing, “the issue is that the topic is not brought up to many to begin with.

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“Among minority populations, it is not just about getting them tested, but rather ensuring they get the correct information in an understandable way so they can pursue the cancer risk management that is best for them. It is not testing itself that leads to patient benefit, but rather acting on the test results, which may enable individuals to be proactive about their health, such that cancers may be prevented or detected early,” she said.

“It has become critical to develop evidence-based guidelines, based on the best evidence we have,” Dr Pal concluded.


1. Beroud C. The BRCA Share™ Consortium. A novel public/private partnership to promote BRCA data sharing. Presentation at: 6th Biennial Meeting of The Human Variome Project; Paris, France; June 1, 2016.
2. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33:3600-3667.
3. National Comprehensive Cancer Network Guidelines. Genetic/Familial High-Risk Assessment: Breast and Ovarian. March 15, 2016. Accessed June 8, 2016.