Clinical Management of BRCA Mutation Carriers
Digital mammography refers to the use of a digital detector to find and record x-ray images. This technology improves contrast resolution, and has been proposed as a potential strategy for improving the sensitivity of mammography. A screening study comparing digital with routine mammography in 6,736 examinations of women aged 40 years and older found no difference in cancer detection rates; however, digital mammography resulted in fewer recalls. In another study (ACRIN-6652) comparing digital mammography to plain-film mammography in 42,760 women, the overall diagnostic accuracy of the two techniques was similar. When receiver operating characteristic (ROC) curves were compared, digital mammography was more accurate in women younger than 50 years, in women with radiographically dense breasts, and in premenopausal or perimenopausal women.
In a prospective study of 251 individuals with BRCA mutations who received uniform recommendations regarding screening and risk-reducing, or prophylactic, surgery, annual mammography detected breast cancer in six women at a mean of 20.2 months after receipt of BRCA results. The Cancer Genetics Studies Consortium task force has recommended for female carriers of a BRCA1 or BRCA2 high-risk mutation, "annual mammography, beginning at age 25 to 35 years. Mammograms should be done at a consistent location when possible, with prior films available for comparison." Data from prospective studies on the relative benefits and risks of screening with an ionizing radiation tool versus CBE or other nonionizing radiation tools would be useful.[21,22,23]
Certain observations have led to the concern that BRCA mutation carriers may be more prone to radiation-induced breast cancer than women without mutations. The BRCA1 and BRCA2 proteins are known to be important in cellular mechanisms of DNA damage repair, including those involved in repairing radiation-induced damage. Some studies have suggested intermediate radiation sensitivity in cells that are heterozygous for a BRCA mutation, but this is not consistent and varies by experimental system and endpoint. A large international case-control study of 1,601 mutation carriers described an increased risk of breast cancer (hazard ratio (HR) = 1.54) among women who were ever exposed to chest x-rays, with risk being highest in women age 40 years and younger, born after 1949, and those exposed to x-rays only before age 20 years. In contrast, two studies of the effect of mammogram exposure on carriers (n = 1,600, n = 162) did not support an association between such exposure and subsequent breast cancer risk.[25,26] In a small study, there was a modest association between lifetime mammogram exposure and risk in BRCA1 mutation carriers (HR = 1.08, P = .03). No significant effect was seen after exclusion of postdiagnosis mammograms. With the routine use of magnetic resonance imaging (MRI) in BRCA1/BRCA2 mutation carriers, any potential benefit of mammographic screening must be carefully weighed against potential risks, particularly in young women. However, at this time there is insufficient evidence to suggest that mutation carriers should avoid mammography, particularly since some breast cancers are identified by mammography and not MRI.