Ionizing radiation exposure
A well-established relationship exists between exposure to ionizing radiation and the risk of developing breast cancer. Excess breast cancer risk is consistently observed in association with a variety of exposures such as fluoroscopy for tuberculosis and radiation treatments for acne, tinea, thymic enlargement, postpartum mastitis, or Hodgkin lymphoma. Although risk is inversely associated with age at radiation exposure, the manifestation of breast cancer risk occurs according to the usual age-related pattern. An estimate of the risk of breast cancer associated with medical radiology puts the figure at less than 1% of the total. However, it has been theorized that certain populations, such as AT heterozygotes, are at an increased risk of breast cancer from radiation exposure. A large cohort study of women who carry mutations of BRCA1 or BRCA2 concluded that chest x-rays increase the risk of breast cancer still further (RR = 1.54; 95% CI, 1.1–2.1), especially for women who were x-rayed before age 20 years.
Women treated for Hodgkin lymphoma by age 16 years may have a subsequent risk, which is as high as 35%, of developing breast cancer by age 40 years.[57,58] One study suggests that higher doses of radiation (median dose, 40 Gy in breast cancer cases) and treatment received between the ages of 10 and 16 years corresponds with higher risk. Unlike the risk for secondary leukemia, the risk of treatment-related breast cancer did not abate with duration of follow-up; that is, increased risk persisted more than 25 years after treatment.[57,59,60] In these studies, most patients (85%–100%) who developed breast cancer did so either within the field of radiation or at the margin.[57,58,59] A Dutch study examined 48 women who developed breast cancer at least 5 years after treatment for Hodgkin disease and compared them with 175 matched female Hodgkin disease patients who did not develop breast cancer. Patients treated with chemotherapy and mantle radiation were less likely to develop breast cancer than those treated with mantle radiation alone, possibly because of chemotherapy-induced ovarian suppression (RR = 0.06; 95% CI, 0.01–0.45). Another study of 105 radiation-associated breast cancer patients and 266 age-matched and radiation-matched controls showed a similar protective effect for ovarian radiation. These studies suggest that ovarian hormones promote the proliferation of breast tissue with radiation-induced mutations.
The question arises whether breast cancer patients treated with lumpectomy and radiation therapy (L-RT) are at increased risk for second breast malignancies or other malignancies compared with those treated by mastectomy. Outcomes of 1,029 L-RT patients were compared with 1,387 patients who underwent mastectomies. After a median follow-up of 15 years, there was no difference in the risk of second malignancies. Further evidence from three RCTs is also reassuring. One report of 1,851 women randomly assigned to undergo total mastectomy, lumpectomy alone, or L-RT showed rates of contralateral breast cancer to be 8.5%, 8.8%, and 9.4%, respectively. Another study of 701 women randomly assigned to undergo radical mastectomy or breast-conserving surgery followed by radiation therapy demonstrated the rate of contralateral breast carcinomas per 100 woman-years to be 10.2 versus 8.7, respectively. The third study compared 25-year outcomes of 1,665 women randomly assigned to undergo radical mastectomy, total mastectomy, or total mastectomy with radiation. There was no significant difference in the rate of contralateral breast cancer according to the treatment group, and the overall rate was 6%.