February 19, 2019
4 min read

USPSTF updates recommendation on screening, counseling, testing for BRCA-related cancer

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Carol M. Mangione, MD, MSPH
Carol M. Mangione

Women who have a family history of certain types of cancer should be screened to determine if they have an increased risk for BRCA1 or BRCA2 mutations, according to a draft recommendation from the U.S. Preventive Services Task Force.

Women with an ethnicity or ancestry linked to these genetic mutations also should be screened.

Those who screen positive should undergo genetic counseling and may receive BRCA testing, according to the task force’s B recommendation, which is consistent with guidelines finalized in 2013.

The task force also released a draft D recommendation for women without a family history, ethnicity or ancestry associated with a higher risk for a BRCA1 or BRCA2 mutation, indicating they should not be screened, counseled or tested.

The task force based the recommendations — consistent with previous guidelines — on a review of dozens of studies found on the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Medline, PsycInfo and Embase.

The studies included 14 that evaluated the accuracy of seven familial risk models used by nonspecialists in issuing referrals for genetic counseling, 28 that evaluated the pros and cons of genetic counseling, and nine that evaluated the efficacy and harms of medications to reduce primary breast cancer in women with increased risks.

“The big change is that we now have another class of medications that can be considered to be used for prevention,” Carol M. Mangione, MD, MSPH, chief of the division of general internal medicine and health services research at David Geffen School of Medicine at University of California, Los Angeles, and member of the task force, told HemOnc Today. “The 2013 recommendation only spoke about tamoxifen and raloxifene, but there have been new studies in the intervening time that made it appropriate to add aromatase inhibitors to that list. Adding medications is always helpful because every medicine has a different profile with benefits and harms. It gives patients and their physicians more choices about what to use, and the treatment can be tailored to that specific patient.”

Determining, reducing risk

Breast cancer is the most common form of cancer among women in the United States and is the second leading cause of cancer-related death, according to the draft recommendation. About 266,120 women in the U.S. received a breast cancer diagnosis last year and 40,920 died of it.

Ovarian cancer, meanwhile, is the fifth-leading cause of cancer death among women in the U.S. About 22,240 American women developed the disease last year and 14,070 died of it.


BRCA mutations occur in one in 300 (0.2%) to one in 500 (0.3%) women in the general population but account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases.

About 6% of women who develop cancer before age 40 years have BRCA mutations, and 2.1% of Ashkenazi Jewish women have the mutations.

In a meta-analysis of studies for which recruitment was based on family history of breast or ovarian cancer, 13.6% of women had a BRCA1 mutation and 7.9% had a BRCA2 mutation. The incidence of either mutation was 19.8%.

“Our body has a natural way of suppressing cancer cells. [The body of] someone who has the BRCA1 or BRCA2 mutation ... naturally isn’t as effective at suppressing cancer cells, so their risk [for] breast, ovarian, fallopian or pararenal cancer is higher,” Mangione said. “The important thing about this recommendation is that the women who are found to be high risk on the screening tool need to be referred to a genetic counselor. After a more rigorous detailed risk assessment, they need to make a decision on whether they want to be tested for the BRCA1 or BRCA2 mutation. If they are positive [for the mutation], then it’s very important they consider all treatments that may help reduce their risk.”

Results of studies

The 14 studies that looked at seven familial risk models for nonspecialists found moderate to high discriminatory accuracy with BRCA1 and BRCA2 mutations or clinical risk standards as reference points. The seven risk models analyzed included the Ontario Family History Assessment Tool, Manchester Scoring System, Referral Screening Tool, Pedigree Assessment Tool, the seven-question Family History Screening, brief versions of BRCAPRO, and the International Breast Cancer Intervention Study instrument.

None of the studies evaluated optimal ages, frequencies or harms of risk assessment.

The 28 studies that evaluated the pros and cons of genetic counseling found that women who had counseling appeared less worried, anxious or depressed about breast cancer. The women also demonstrated an increased understanding of their risk for breast cancer and less inclination to undergo inappropriate mutation testing.

One randomized controlled trial found that population-based testing among Ashkenazi Jewish individuals detected more BRCA1 and BRCA2 mutations than testing based on family history.

The nine randomized controlled trials that evaluated the efficacy and harms of medications to reduce primary breast cancer in women with increased risks found lower incidence of invasive breast cancer with tamoxifen (RR = 0.69; 95% CI, 0.59-0.84; four trials), raloxifene (RR = 0.44; 95% CI, 0.24-0.8; two trials), and aromatase inhibitors anastrozole and exemestane (RR = 0.45; 95% CI, 0.26-0.7; two trials) after 3 to 5 years of use compared with placebo.


Tamoxifen had a greater effect than raloxifene in one study comparing the two drugs (RR = 1.24; 95% CI, 1.05-1.47).

There were no randomized controlled trials that evaluated the efficacy of intensive screening for breast or ovarian cancer in women with BRCA1 or BRCA2 mutations. However, observational studies found that false-positive rates, unnecessary imaging and unneeded surgeries were higher for women who underwent intensive screening.

Most women in the studies had no anxiety after screening with MRI, mammography or clinical breast exams.

“Breast cancer is the second-leading cause of death in women behind lung cancer, so this is a highly prevalent condition,” Mangione said. “We know from studies that most primary care doctors are not routinely having this conversation with women or assessing risks or offering medication to the high-risk women. One of our hopes with this recommendation is that we heighten the awareness that it’s a good idea to make an assessment to determine if someone is high risk.”– by John DeRosier

For more information:

Carol Mangione, MD, PhD, can be reached at University California, Los Angeles, Suite 420, 200 UCLA Medical Plaza, Los Angeles, CA 90095.

Disclosures: Mangione reports no relevant financial disclosures.