BRCA Mutation Testing Increasing in Younger Women

Fran Lowry

February 17, 2016

The proportion of women diagnosed with breast cancer at 40 years of age or younger who undergo BRCA1 and BRCA2 mutation testing is increasing, according to a new study.

In fact, the proportion went from 77% in 2006 to 95% in 2013, Shoshana M. Rosenberg, ScD, MPH, from the Dana-Farber Cancer Institute in Boston, and colleagues report in their study, which was published online February 11 in JAMA Oncology.

The team looked at trends and the frequency of BRCA1 and BRCA2 genetic testing in 897 participants in the ongoing prospective cohort study known as Helping Ourselves, Helping Others: Young Women's Breast Cancer Study.

Overall, 780 (87%) of the women underwent testing for BRCA1 and/or a BRCA2 mutations in the year after their diagnosis.

A Striking Finding

Eighty-seven percent is a substantial proportion. "That was one of the most striking findings from our research," senior author Ann H. Partridge, MD, MPH, from the Dana-Farber Cancer Institute, said in an author interview posted on the JAMA Oncology website.

Treatment decisions were influenced by genetic status, and 86% of mutation carriers opted to undergo bilateral mastectomy.

However, 50% of women without a BRCA1 or BRCA2 mutation also opted for bilateral mastectomy. This is "a surprising result," Dr Partridge said.

Dr Ann Partridge

Only 117 women (13.0%) reported not undergoing testing for BRCA mutations. Of these, 28 (24.0%) said they did not think they were at risk for a mutation, and a similar proportion said they were not tested because their physician thought it was unlikely they had a mutation. In addition, 15 women (12.8%) cited concerns about potential insurance or work issues as a result of a positive test, 13 (11.1%) cited the inability to pay for testing, and 21 (17.9%) said they did not consider testing to be a priority. However, 43 (36.8%) of the untested women said they were thinking about getting tested in the future.

"We need to develop supports and education to help women digest this information and to make sure they are making the best values-based decisions, and not making decisions based on sometimes unclear understandings of what the genetic findings mean," Dr Partridge explained.

Encouraging Results

Dr Jeffrey Weitzel

"It is encouraging to see the integration of [genetic cancer risk assessment] into standard-of-care clinical treatment of breast cancer over the past 2 decades," Jeffrey N. Weitzel, MD, from the division of clinical cancer genetics at City of Hope in Duarte, California, and coauthors write in an accompanying editorial.

"We are very happy about the reach of this study," Dr Weitzel told Medscape Medical News.

"The sampling is very broad, going from 2006 to 2014, and the uptake of genetic testing was 87%, which is reasonable, given there are expected to be certain individuals who may not participate out of their own personal beliefs, which we need to respect," he said.

The high rate of testing in this cohort of women probably reflects the fact that they are from a more advantaged demographic, Dr Weitzel pointed out.

This is a "better-educated group of women who are more able to get this kind of care," he explained. "We already know that individuals in lower socioeconomic strata and other culturally disadvantaged populations do not have that kind of access."

Dr Weitzel and his colleagues have set up a clinic at Olive View, a nearby community hospital in the San Fernando Valley that treats many disadvantaged Latina women.

Their experience has taught them that offering BRCA testing is feasible and acceptable in this ethnic population.

"We started our clinic about 12 years ago, after noticing young Latinas, 32-year-olds, coming in with very large tumors who might very well have had a family history of breast cancer but who did not have any access to cancer risk counseling or testing," he said.

The clinic has been a success.

"There's no doubt in my mind that ethnic populations are receptive to genetic testing and counseling if it's provided in a culturally sensitive manner that is adapted and coherent with their belief systems. They will be participants, but it takes effort," Dr Weitzel said.

He noted that the fact that some of the women did not undergo genetic testing because their doctors did not believe they needed it is rather alarming.

"The National Comprehensive Cancer Network [NCCN] guideline has recommended BRCA1 and BRCA2 testing for all women below the age of 40. It is disconcerting to me that any of the physicians would say they didn't think it was necessary for a woman who met this single criterion, which could not be more clear, to undergo such testing. This shows that we still have some training to do in terms of professional education for clinicians," Dr Weitzel said.

Patients are guided by their physicians; they are among the biggest influencers of a patient's decisions to participate in genetic testing, he added. "If the physician is not going to participate in genetic testing, the patient is not going to participate. We've been training community-based physicians at City of Hope, with some NCCN support, so we are building an infrastructure, but clearly, we need to do more."

Another alarming finding from the study is the high rate of double mastectomy among women who had no BRCA genetic mutations.

"Half of the women who were BRCA-negative still chose a bilateral mastectomy, which reflects a bigger trend across the United States of the increasing uptake of bilateral mastectomy among younger women. We have a concern about this, as do the authors," Dr Weitzel said.

This trend for bilateral mastectomies has been previously reported by Medscape Medical News.

There has always been a misconception among some women with breast cancer that, somehow, doing more surgery would help them be free of disease or be cured of the disease, Dr Weitzel pointed out.

"It turns out that removing the other breast does not change their mortality. It may prevent new cancers in the other breast, but they don't understand that; they don't realize that breast cancer doesn't cross the midline," he explained. "But suddenly being diagnosed with a life-threatening disease when you are young is a terrible shock. What could be more frightening? What kind of decision are these young women going to make in such a setting?"

"Many times, the decision will not be rationally based, but fear-driven. We need to understand how we can better support these women from a psychological perspective," he said.

Providing the appropriate emotional and decision-making support could help reduce the inappropriate use of double mastectomy, Dr Weitzel noted.

There might be a small subset of women who chose bilateral mastectomy, despite being BRCA-negative, who have other genetic indicators of risk, he said.

These include women who have undergone multigene panel testing that has shown that they have other gene mutations, such as a PALP2 or TP53, which is indicative of an increased risk for breast cancer.

"There are other genetic etiologies of breast cancer beyond BRCA, so perhaps all of those double mastectomies were not unjustified. Also, for some women, there may be a pragmatic reason for getting a bilateral mastectomy. For example, their reconstructive doctor might have advised the procedure, saying they were better off starting from scratch, rather than having to try to build and sculpt, which is not based on future risk but a practical reason," he said.

"I thought this paper was simple to start with, but it does bring up many topics that are worth discussing," Dr Weitzel said.

"We need to extend the reach of testing so that everyone can benefit, including those who are underserved. We need to try to understand the factors that are driving the bilateral mastectomy problem and also how we can help women make risk appropriate decisions. All these are valid concerns, but the bottom line is that we are very happy to see that we are finally getting to the point where we are reaching most newly diagnosed patients who are candidates for testing," he said.

This study was funded by the Susan G. Komen for the Cure, the National Institutes of Health, and The Pink Agenda. Dr Rosenberg, Dr Partridge, and Dr Weitzel have disclosed no relevant financial relationships.

JAMA Oncol. Published online February 11, 2016. Abstract, Editorial


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