Testing for genetic mutations strongly associated with an increased breast cancer risk has risen dramatically among women younger than age 40 who are diagnosed with the disease, according to a new study.

Overall, within a year of their diagnosis, 87 percent of the women in the Young Women’s Breast Cancer Study were tested for mutations in the BRCA1 and BRCA2 genes. Mutations in either of these genes increase a woman’s lifetime risk of breast cancer, her risk of developing breast cancer at a younger age, and her lifetime risk of ovarian cancer.

The percentage of women who underwent testing gradually increased over the 7-year study period, from approximately 77 percent of those diagnosed in 2006 to nearly all women in 2013.

Shoshana Rosenberg, Sc.D., of the Dana-Farber Cancer Institute, and her colleagues reported the findings February 11 in JAMA Oncology.

Current Trends in BRCA Testing

The presence of a harmful BRCA gene mutation can not only influence a patient’s treatment decisions but also have implications for a patient’s family members. So clinicians often encourage young women diagnosed with breast cancer to be tested for BRCA mutations.

Several older studies found that rates of BRCA mutation testing were low in younger women diagnosed with breast cancer, approximately 20 to 25 percent, Dr. Rosenberg and her colleagues noted. However, the visibility of BRCA testing has gained attention in recent years, due in part to legal battles related to patents on BRCA genetic tests themselves and also to actress Angelina Jolie’s revelation in May 2013, that she had a preventive double mastectomy after learning she had a harmful BRCA1 mutation. (Jolie had the testing done because of her strong family history of breast cancer.)

The current study included nearly 900 women diagnosed with breast cancer at age 40 or younger between August 2006 and December 2013 who were treated at 11 academic or community medical centers.

In the study’s first 2 years, between 70 and 80 percent of participants were tested within a year of their diagnosis. That percentage jumped substantially in the ensuing years, with all but a handful of women diagnosed in 2012 and 2013 undergoing testing (96.6 percent and 95.3 percent, respectively). Approximately 80 percent said they received their test results within 3 months of their diagnosis.

"Greater public awareness may have made women more likely to bring up the issue of genetic risk with their physicians, possibly resulting in more testing," Dr. Rosenberg said in a news release.

Approximately 30 percent of women who were tested and had a positive or negative result (some women had an indeterminate finding) reported that it influenced their cancer treatment. In this group, 86 percent of those who had a BRCA mutation had both the affected breast and the healthy breast surgically removed (bilateral mastectomy), as opposed to only having the affected breast removed; 53 percent also had their ovaries and fallopian tubes removed (salpingo-oophorectomy).

Slightly more than half of the women in this group who did not have a mutation also had a bilateral mastectomy, although only a few had a salpingo-oophorectomy.

Of the women who did not undergo BRCA mutation testing, nearly half said it was because they did not think they were likely to have a mutation or that their physician felt that they were unlikely to have a mutation.

The findings, the authors noted, likely don’t reflect the rate of BRCA testing among younger women treated in the community setting. For example, nearly all of the study participants had health insurance and all were "treated at cancer centers where comprehensive genetic counseling and testing services are widely available," they wrote.

"In the community setting, patients are more likely to have concerns about health insurance and cost of testing. The rate of BRCA testing would likely be lower, in that case." said Lyndsay Harris, M.D., of NCI’s Division of Cancer Treatment and Diagnosis. There may also be less awareness about recommendations for BRCA testing in the community setting, Dr. Harris continued.

Multigene Testing and Treatment Choices

In an accompanying editorial in JAMA Oncology, Jeffrey Weitzel, M.D., of the City of Hope Cancer Center in Duarte, California, and his colleagues noted that they were "heartened" to see that more young women diagnosed with breast cancer were undergoing recommended genetic cancer risk assessment. But the findings weren’t all positive, they continued.

"It is disconcerting that 48 percent of those who did not get testing indicated that they and/or their physician did not think a BRCA mutation was likely," they wrote.

Dr. Harris also noted the high rate of bilateral mastectomy, particularly in women without a BRCA mutation.

"Surveillance and preventive agents are still very acceptable, even in BRCA mutation carriers," she said. "So it raises the question of whether there is bias in the way the women are being informed about their options."

The authors agreed that the relatively high number of women in the study without BRCA mutations who underwent bilateral mastectomy "might also suggest a need for better communication of the relatively low risk of contralateral breast cancer among women who are noncarriers … and that bilateral mastectomy is not associated with improved survival."

Women diagnosed with breast cancer are also expanding their use of other genetic tests, Dr. Weitzel and his colleagues wrote. Next-generation sequencing "has ushered in a new era" of testing for genetic alterations aside from BRCA mutations that studies have linked to increased breast cancer risk, they noted.

Some of the women in this study may have had a genetic alteration identified by one of these multigene tests, such as a mutation in the p53 tumor suppressor gene, that increases their risk enough "to justify consideration" of a bilateral mastectomy, they wrote.

But "many of the moderate- and low-penetrance genes currently included on multigene panels do not reach a level of risk to justify" the procedure, they cautioned.

Posted by the National Cancer Institute
January 1, 2016