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, exam ining the effect of radiotherapy (RT), which causes double-strand breaks, o n breast tissue from BRCA 1/2 mutation carriers. Thus the goals of this stu dy were to compare rates of radiation-associated complications, in-breast t umor recurrence, and distant relapse in women with BRCA 1/2 mutations treat ed with breast-conserving therapy (BCT) using RT with Kites observed in spo radic 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 t a 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 Organizati on for Research and Treatment of Cancer toxicity scaring, there were no sig nificant differences in acute or chronic morbidity in skin, subcutaneous ti ssue, lung, or bone. The 5-year actuarial overall survival, relapse-free su rvival, and rates of tumor control in the treated breast for the patients i n 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 seq uelae in breast tissue heterozygous for a BRCA 1/2 germline mutation compar ed with controls, and rates of tumor control in the breast and survival wer e comparable between BRCA 1/2 carriers and controls at 5 years. Although ad ditional follow-up is needed, these data may help in discussing treatment o ptions in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers o f a germline BRCA 1/2 mutation. J Clin Oncol 18:3360-3369. (C) 2000 by Amer ican Society of Clinical Oncology.