Is Mammography Indicated for Women With Defective BRCA Genes? Implications of Recent Scientific Advances for the Diagnosis, Treatment, and Prevention of Hereditary Breast Cancer

Bernard Friedenson, PhD Department of Biochemistry and Molecular BiologyUniversity of Illinois ChicagoChicago, Illinois

In This Article

Implications for Diagnosis

There is a clear link between radiation exposure and breast cancer in normal women,[6,7] and the premise that mammography might be dangerous was rampant many years ago. A recent estimate of the risk for the normal population is based on annual mammograms at an accredited facility.[8] The data shown in the Table begin at age 30 and assume a mean glandular dose of 0.1 rad per view for 2 views per breast.[6,7,8] Dosages 3 times higher are permitted, and this would raise the risk 3-fold.[7,8]

Table. Estimated Risk of Mammogram-Induced Cancer

Age at Annual Exam (yrs) Risk of Mammogram-Induced Cancer [for normal women]
30-34 1 in 220
35-49 1 in 190
50-64 1 in 133

This estimate makes the assumption that risk accumulates. Therefore, the risk from multiple mammograms is the sum of the risk from each individual exam, which amounts to a total increase in risk at age 64 of <1% (see Table). Many experts agree that the benefits of increased detection would outweigh this increase in risk. Although these data are obtained only from a normal population, current policies for management and screening of BRCA-1/2 mutation carriers also require annual or semiannual mammography beginning by age 25[9] or 10 years sooner than the first diagnosed case in the family.[3]

Relatively low doses of x-rays cause single- and double-strand breaks in DNA. Ionizing radiation also damages DNA bases and results in the loss of bases. The damage is dose dependent and probably extrapolates down to dosages similar to those in mammography.[10] Normal women (ie, women with normal BRCA genes) do not get very many radiation-induced cancers from mammograms, because normal women have DNA repair systems that adequately reverse the DNA damage that occurs. When DNA lesions are inadequately or incorrectly repaired, the lethal and mutagenic effects of ionizing radiation show up.[10] Damaged DNA repair is already strongly implicated in causing hereditary colon cancer[11] and other types of tumors.

A large and growing body of evidence shows that BRCA-1 and BRCA-2 gene products are both involved in repairing damaged DNA.[4,5] This is the basis for the prediction here that women with BRCA1/2 gene defects will be less able to repair radiation damage to their DNA than women without such defects. The finding that a lack of functional BRCA-1 and BRCA-2 led to defective repair of DNA double-strand breaks in irradiated cells supports this prediction.[12]

Moreover, defects in BRCA-1/2 would allow DNA mutations to accumulate more rapidly than normal. Because some sets of these DNA mutations cause breast cancer, one would predict that women with defective BRCA-1/2 will get breast cancer at a younger age. Although there is currently no epidemiologic evidence that ties the age of onset of tumors related to abnormal BRCA-1/2 directly to defective DNA repair or to radiation exposure, Wagner and associates[13] found that 39.5 years was the median age for discovery of these tumors. By contrast, 80% of sporadic breast cancers occur in women over age 50. The incidence of sporadic breast cancer increases with age, up to a maximum incidence at age 75-79 (0.5%); this still does not approach the incidence in young women with mutated BRCA-1/2 genes (50%-87%)[14]

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