Evidence-Based Oncology

USPSTF Recommends BRCA Testing in Women Based on Familial History

Published Online: March 20, 2014
Surabhi Dangi-Garimella, PhD
In late December of 2013, the US Preventive Services Task Force (USPSTF) provided an update to its 2005 recommendations, reaffirming the genetic risk assessment and breast cancer susceptibility gene (BRCA) mutation testing in women susceptible to breast and ovarian cancers in women, the most common and ninth-most common cancers in US women, respectively.

The task force recommends that women whose family members have been diagnosed with breast, ovarian, tubal, or peritoneal cancers be screened to identify a family history that may be associated with an increased risk of potentially harmful mutations in BRCA1 or BRCA2, the well-identified breast cancer susceptibility genes. Women with positive screening results are advised to undergo genetic testing, but only following genetic counseling. Further, women who lack a family history of an increased risk for BRCA mutations are specifically advised against genetic counseling or BRCA testing (Figure).1 In an e-mail response, Virginia Moyer, MD, MPH, chair of the USPSTF, informed Evidence-Based Oncology that the Task Force is currently in the process of updating the 2009 recommendation of biennial screening mammography for women aged 50 to 74 years.

Etiology of the BRCAAssociated Disease

BRCA1 and BRCA2 are tumor-suppressor genes that were discovered in 1994 and 1995, respectively. Germline mutations in these genes predispose to ovarian and breast cancer, while somatic mutations have also been found to result in numerous cancers.2 The proteins translated from these 2 genes lack structural homology, but are actively associated with DNA repair; so functionally defective BRCA1 and BRCA2 would result in faulty DNA repair mechanisms.3

Individuals with germline mutations in BRCA1 or BRCA2 genes have been shown to have an increased susceptibility to certain cancers: 45% to 65% of females with the mutation may develop breast cancer while 11% to 39% may develop ovarian cancer.4 An increased susceptibility to pancreatic adenocarcinoma5 has also been identified in individuals carrying either of the mutations, while BRCA1 mutation carriers in the United States, Canada, or Europe, below the age of 50 years, were recently shown to carry an increased risk of early-onset colorectal cancer.6 The association between BRCA1 mutation and the risk of colorectal cancer holds significant importance in terms of the current USPSTF recommendations for the cancer. The current guidelines recommend testing beginning at age 50 years and up to age 75 years for the general population, but those with an increased risk are advised to undergo early and more frequent testing.

However, based on the results of this study, women with BRCA1 mutation should initiate screening for colorectal cancer at age 40 years.6,7

Counseling for Cancer Survivors

The current task force recommendations are aimed at women previously undiagnosed with breast or ovarian cancer, but with a familial history. Ellen Matloff, MS, director of cancer genetic counseling at Yale Cancer Center, strongly believes that “these prevention guide-lines should include patients, male and female, who are cancer survivors and would like to prevent the development of a future primary cancer.” Working in collaboration with the nonprofit organization Facing Our Risk of Cancer Empowered (FORCE), Matloff raised concerns and made suggestions to the USPSTF regarding the reach of the current guidelines.8

However, the task force responded that recommendations for cancer survivors, although important, would encompass disease management, which falls outside of the scope of their current recommendations and are aimed at preventive services in the general population with no symptoms of disease.8

BRCA Mutations in Men, and Risk of Cancer

Numerous studies have documented an increased risk of cancer among men with BRCA1/2 mutations. A study conducted among male breast cancer patients in Canada found a strong association between familial history (at least 1 first- or second-degree relative with breast cancer), BRCA2 mutation (2 of 14 patients) and a previous history of other cancers prior to the breast cancer diagnosis, 9 while another study in Ashkenazi men found an increased risk of prostate cancer in BRCA2 mutation carriers.10 A recent study recognized poor overall survival in BRCA2 mutation–carrying prostate cancer patients with multiple breast cancer relatives.11

Says Matloff, “The guidelines stress throughout that women should have genetic counseling and testing. Unfortunately, this perpetuates a pervasive and dangerous myth in the patient, lay, and medical communities that a family history of breast and ovarian cancer somehow applies only to women…Statements like this gloss over the critical fact that a male who is a BRCA carrier may have daughters, granddaughters, and other female relatives at risk who can be helped by identifying the BRCA mutation in the family. We should not discriminate against males and should offer them the genetic counseling and testing services available to women.”

However, according to Moyer, USPSTF currently has no recommendations on counseling and testing for men with BRCA mutations as there has yet to be a thorough examination of the available


Physician Awareness and Involvement

With an upsurge in the research and awareness on hereditary cancer risks (approximately 5%-10% of cancers are hereditary in nature), family physicians are paying increased attention to family history and referring high-risk patients to genetic counseling and testing. Early detection and intervention can lead to preventive measures—such as prophylactic mastectomy; awareness of this procedure increased due to the so-called  “Angelina effect”12 after actress Angelina Jolie announced last spring she had both breasts removed due to the presence of a BRCA mutation and the loss of several close relatives from breast cancer.

PDF is available on the last page.