Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations

Purpose: Recent laboratory data suggest a role for BRCA 1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA 1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA 1/2 mutations treated with breast-conserving therapy (BCT) using RT with Kites observed in sporadic disease. Patients and Methods: Seventy-one women with a BRCA 1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used ta compare matched cohorts for rates of complications and recurrence. Results: Tumors from women in the genetic cohort were associated with high histologic (P =.0004) and nuclear (P =.009) grade and negative estrogen (P =.0001) and progesterone (9 =.002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scaring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). Conclusion: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA 1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA 1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA 1/2 mutation. J Clin Oncol 18:3360-3369. (C) 2000 by American Society of Clinical Oncology.