Expert Explains USPSTF Update of BRCA Screening Guidelines

Carol Mangione, MD, MSPH

Women with ancestry associated BRCA mutations as well as those with a personal or family history of specific malignancies should undergo a BRCA risk assessment, according to a recently released recommendation statement issued by the United States Preventive Services Task Force (USPSTF).¹

Additionally, for women who have high-risk assessments, the USPSTF recommends genetic counseling and potential genetic testing for BRCA.

The USPSTF's recommendation statement, which are additions to their 2013 statement, is related to risk assessment, genetic counseling, and genetic testing to improve outcomes for patients with BRCA1/2-positive breast cancer. The updated recommendations provide further information about properly screening patients based on the ancestral or personal and family history.

According to Susan Domchek, MD, executive director of the Basser Center for BRCA at the Abramson Cancer Center at the University of Pennsylvania, healthcare providers must stay on top of the progressive area of genetic testing. "The medical community needs to consider what genetic health data is truly helpful to a patient, strive to test those who may be genetically predisposed to an increased risk of cancer, and work to educate patients and providers on how to correctly and effectively use their test results to make better healthcare decisions," said Domchek in a statement.²

Even with these well-researched recommendations, USPSTF members still see more work to be done, which will come from a better understanding of BRCA mutations and how they may differ across different ethnic groups.

In an interview with OncLive, Carol Mangione, MD, MSPH, division chief of general internal medicine and health services research and professor of medicine, University of Californa, Los Angeles Health, and a co-author on the USPSTF recommendation statement, gave insight into the specifics of the recommendations and how the USPSTF hopes these suggestions will impact patient outcomes.

OncLive: Can you explain the rationale behind releasing this recommendation statement?

Mangione: Every year, too many American women are faced with the challenge of dealing with a cancer diagnosis related to potentially harmful mutations of the BRCA1 and BRCA2 genes. However, the Task Force found that there are several steps women can take to determine if they're potentially at increased risk for BRCA gene mutations, and if genetic counseling and BRCA testing are needed.

The Task Force recommends that women who have a personal or family history of certain types of cancer—or who have ancestry associated with BRCA mutations—should have their risk assessed for BRCA mutations. If this assessment suggests that a woman is at increased risk, she should receive genetic counseling and, if indicated after counseling, BRCA genetic testing. It is important to remember that while some women can benefit from risk assessment, counseling, and testing, these services are not for everyone. If a woman does not have a personal or family history or ancestry associated with BRCA mutations, she [does not need to] undergo risk assessment, genetic counseling, or genetic testing for BRCA-related mutations.

Can you discuss the review of studies on the effectiveness of genetic counseling, genetic testing, and interventions?

The Task Force reviewed evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with a BRCA-related cancer, as well as women with a previous breast, ovarian, tubal, or peritoneal cancer diagnosis who have completed treatment and are considered cancer-free. The Task Force also reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmful BRCA1/2 mutations, including intensive cancer screening, medications, and risk-reducing surgery.

What are some of the benefits to genetic screening before, during and after treatment?

First of all, when we compare these recommendations to the 2013 USPSTF recommendation, there are 2 new groups that are specifically identified for screening. One group are women who have ancestry that's associated with a higher chance of having BRCA1/2 mutation. The good news is that in the overall population, we know that the proportion of women who have these mutations is well under 1%. It's about 0.2% to 0.3%. But we know there are certain groups of women, particularly those who have Ashkenazi Jewish heritage, where the likelihood of the mutation is closer to 2% to 3%. So, having studies of adequate quality that show the increased prevalence in this group allows us to add ancestry as a risk factor and encourage those women to be screened in primary care and to consider seeing a genetic counselor and getting BRCA testing.

The other group that the 2019 recommendation identifies at increased risk are women who have a history of having had breast cancer, ovarian cancer, tubal, or peritoneal cancer and are now considered cancer-free.

The Task Force focuses on recommendations that can be implemented in primary care. In primary care settings, many doctors have women who might have had breast cancer in their early 40s who were successfully treated and now they are in their 50s and no longer seeing an oncologist but are cared for in primary care. If these women never got screened for BRCA1 or BRCA2 when they had their cancer diagnosis, our new recommendation is that they consider screening at this point in time.

What subgroups of patients stand to have the most benefit if physicians follow these recommendations?

I would say the groups that would have the greatest benefit are the women who have ancestry or a personal or family history of having had breast cancer, ovarian cancer, tubal or peritoneal cancers in the past. Those are the women who have the greatest likelihood of screening positive on the brief primary care questionnaire and of getting referred to a genetics counselor so that they can make an informed decision about whether they want to have BRCA tested or not, given their personal circumstance.

What challenges exist with genetic counseling and testing for BRCA1/2?

The biggest challenge is that in many parts of the country, and for women with different types of insurance, they may have trouble accessing genetic counselors. There aren't a lot of genetic counselors that practice in rural parts of the country and certainly for women who might be cared for in the safety net, it's very possible that there aren't enough genetic counselors to do all of this work. The good news is that we found studies to suggest that telephonic counseling is also very effective for implementing this plan. But, I think, one of the challenges would be access to genetic counselors.

[Another important barrier is that primary care physicians don't always remember to ask about these kind of cancers in the patient's family when they take the patient's medical history.]

There is also a barrier in terms of public and primary care doctor knowledge about who they need to be considering for assessment with a short, validated questionnaire. In primary care, we have a lot of competing demands on our time. So, even though these are short screeners and they've been shown to work well, many primary care doctors are trying to get a lot accomplished in that 15-minute visit and screening for who should be tested for BRCA is happening in the context of many other needed services.

Can you discuss the revisions to the statement and how these revisions came about?

Every one of the USPSTF recommendations always gets published first in draft form and there's a 4-week window when anyone in the public can comment on the recommendations and raise issues potentially about other research or wording. The Task Force reviews and takes all of those comments very seriously.

In this case, the final recommendation is very similar to the draft recommendation. I think that our main changes were implemented to improve the clarity of the recommendation rather than changing the main content of the recommendation.

[For example], we were asked for more information on the brief risk assessment tools. If you look at the publication in JAMA, you'll see that there's a series of tables that show the actual tools. That was one thing that the public asked for. We were also asked to be clear about what population was specifically covered under the B recommendation. So, we tried to make that language clear.

In the future, are there any plans to incorporate the recommendations of some of the leading oncology organizations who see room for improvement?

Of course. The main thing is that the Task Force has a very standardized and unbiased way of looking at research in the medical literature whenever we're updating or developing new recommendations and we certainly saw some important gaps in the scientific literature when we were updating this recommendation.

For example, we know that African American women get breast cancer twice as often as [Caucasian] women in this country. We also know that African American women are more likely to get a more serious form of breast cancer and some African American women are BRCA-positive. We know this from studies of women who have breast cancer but what we don't know is the background population prevalence of BRCA mutations in African American women or Latinas. [We also] don't know which BRCA mutations confer increased risk for women from different ancestries.

We need more data on the population prevalence of BRCA mutations in groups of women who disproportionately are getting breast cancer at higher rates than the population average, and in the case of African American women, are more likely to get a serious form of breast cancer. That is a big knowledge gap and the Task Force is hopeful that future research will close this gap so that future evidence-based recommendations [can] decrease the risk of these cancers among all women who are at increased risk because of genetic mutations.

There's some studies showing that BRCA is also associated with some forms of prostate cancer. Our recommendation is focused on women because that's where the strongest and best studies were, but we need to learn more about the risks of male offspring in families where there are known BRCA mutations. ln the recommendation, we also describe some other examples of research gaps that we would like to see filled.

How do you want community oncologists to follow through on your recommendation statement?

The USPSTF mandate is to make recommendations for primary care providers to improve the health of people in the nation. But, for recommendations such as BRCA risk assessment, access to genetic counselors and then consideration of the treatments to reduce risk among women who are BRCA-positive is where community oncologists play critical roles in guiding women through their options and treatment decisions.

Once a woman is identified as BRCA-positive, there are many treatment decisions they will want to consider. Some women will elect to have a mammography once a year and an MRI at the 6-month mark. These conversations about whether to be screened more often, or to consider having a surgery to prevent cancer, or to consider taking a medication to reduce the risk for cancer are complex and require meeting with specialists. Community oncologists and their specialty organizations have a huge role to play in terms of the actual treatment and the choice of those treatments that women might want to consider reducing their risk of getting one of these cancers.

What changes do you anticipate in this space as a result of this Recommendation Statement?

One in 8 women in the United States will get breast cancer and it's the second leading cause of cancer in women. I hope that with time we have more markers or different markers that help us know which women are at the greatest risk and should consider treatments to reduce their risk.

References

1. Owens DK, Davidson KW, Krist AH, et al. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer. JAMA. 2019;322(7):652-665. doi: 10.1001/jama.2019.10987.
2. BRCA1/2 Genetic Testing Recommendations Still Leave Issues Unresolved [press release]. Philadelphia, PA: Penn Medicine; August 20, 2019. https://bit.ly/2HmnewR. Accessed August 26, 2019