With the courageous public revelation of her decision for prophylactic bilateral mastectomy due to her BRCA deleterious mutation status, actress Angelina Jolie has brought into the public eye testing to determine genetic risk for developing breast cancer.

About two percent of women in the general population have a family history suggesting they might carry the BRCA1 or BRCA2 deleterious gene mutation.¹

Those carrying a clinically important BRCA mutation have an estimated probability of developing breast or ovarian cancer by age 70 of 35 to 84% for breast cancer and 10 to 50% for ovarian cancer.¹

Among women with BRCA1 or BRCA2 mutations, prophylactic mastectomy or oophorectomy decreases the incidence of breast and ovarian cancer. There is inadequate evidence for mortality benefits. Chemoprevention with selective estrogen receptor modulators may decrease the incidence of estrogen receptor-positive breast cancer. However, it is also associated with adverse effects such as pulmonary embolism, deep venous thrombosis, and endometrial cancer. Most breast cancer associated with BRCA1 mutations is estrogen receptor-negative and thus not prevented by tamoxifen. Intensive screening with mammography has poor sensitivity and there is no evidence of benefit of intensive screening for women with BRCA1 or BRCA2 gene mutations. Magnetic resonance imaging (MRI) may detect more cases of cancer, but the effect on mortality is not clear.¹

HCPCS code S3820 covers complete BRCA1 and BRCA2 gene sequence analysis as a once-in-a-lifetime benefit for PHC members. This test requires a Treatment Authorization Request (TAR) that meets one of the following requirements:

1. For women without a diagnosis of breast or ovarian cancer:

• Two first-degree relatives with breast cancer, one of whom was diagnosed at 50 years of age or younger, or
• A combination of three or more first- or second-degree relatives with breast cancer regardless of age at diagnosis; or
• A combination of both breast and ovarian cancer among first- and second-degree relatives; or
• A first-degree relative with bilateral breast cancer; or
• A combination of two more first- or second-degree relatives with ovarian cancer, regardless of age at diagnosis; or
• A first- or second-degree relative with both breast and ovarian cancer at any age; or
• A history of breast cancer in a male relative; or
• For women of Ashkenazi Jewish descent, any first-degree relative (or two second-degree relatives on the same side of the family) with breast or ovarian cancer

2. A family history of breast or ovarian cancer that includes a relative with a known deleterious BRCA mutation.

3. Personal history of breast cancer plus one of the following:

• Diagnosed at 45 years of age or younger; or
• Diagnosed at 50 years of age or younger with more than one close blood relative with breast cancer diagnosed at 50 years of age or younger and/or close blood relative with epithelial ovarian/fallopian tube/primary peritoneal cancer; or
• Two breast primaries when first breast cancer diagnosis occurred prior to 50 years of age; or
• Diagnosed at any age, with more than two close blood relatives with breast and/or epithelial ovarian/fallopian tube/primary peritoneal cancer at any age; or
• Close male blood relative with breast cancer; or
• Personal history of epithelial ovarian cancer/fallopian tube /primary peritoneal cancer; or
• For an individual of ethnicity associated with higher mutation frequency (for example, founder populations of Ashkenazi Jewish, Icelandic, Swedish, Hungarian, or other), no additional family history may be required.

4. Personal history of epithelial ovarian cancer/fallopian tube/primary peritoneal cancer.

5. Personal history of male breast cancer.

Genetic counseling should be strongly considered in those found to be carrying a BRCA deleterious mutation. Physicians approved by Medi-Cal through the genetic provider credentialing process may be reimbursed for genetic counseling services using HCPCS S0265.

Marshall Kubota, MD

1. Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility, U.S. Preventive Services Task Force, Annals of Internal Medicine, September 6, 2005.