Radiation Therapy and Risk for Contralateral Breast Cancer

For many years, women with BRCA1/2 pathogenic germline mutations and breast cancer identified in one breast have made shared decisions with their surgeons to undergo bilateral mastectomy. More recently, some women elect to conserve the contralateral breast by undergoing radiation therapy (RT) to the affected breast and no intervention to the unaffected breast. This approach is supported by database and meta-analytic studies showing that breast-conserving therapy compared with mastectomy is associated with no differences in disease-free survival, local recurrence rate, breast cancer–specific survival, or overall survival. Still, a greater risk for contralateral breast cancer (CBC) has been reported in BRCA1/2 carriers with breast cancer diagnoses (BRCA1, 40% and BRCA2, 26%; JAMA 2017; 317:2402). Several factors can increase this risk, including younger age at first diagnosis and number of first-degree relatives under age 50 with breast cancer. To address whether RT also contributes to CBC risk, researchers analyzed data from the International BRCA1/2 Carrier Cohort Study.

The current analysis involved 3602 patients with primary breast cancer and deleterious BRCA1/2 mutations; 2297 patients (64%) received RT. During a median follow-up of 9.6 years, CBC occurred at least 3 months after breast cancer diagnosis in 252 patients who had received RT, of whom 180 had invasive cancers, and in 98 patients who had no RT, with 70 invasive cancers. CBC risk was significantly associated with RT in women with a BRCA2 mutation (hazard ratio, 1.44); a nonsignificant trend was seen in women with BRCA1 mutations. The peak risk for a second event was 5 to 6 years after the index cancer.