Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations

• DOI: 10.1200/jco.2000.18.19.3360
• Publication Date: 2017-02-24T09:24:33Z
• Authors: Lori J. Pierce; Myla Strawderman; Steven A. Narod; Ivo Oliviotto; Andrea Eisen; Laura Dawson; David Gaffney; Lawrence J. Solin; Asa Nixon; Judy Garber; Christine Berg; Claudine Isaacs; Ruth Heimann; Olufunmilayo I. O...; Bruce Haffty; Barbara L. Weber
• Keywords: Adult; BRCA2 Protein; Ovarian Neoplasms; Radiotherapy; Genes, BRCA1; Breast Neoplasms; Neoplasms, Second Primary; Middle Aged; Survival Analysis; Neoplasm Proteins; 3. Good health; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Humans; Female; Neoplasm Recurrence, Local; Radiation Injuries; Germ-Line Mutation; Aged; DNA Damage; Retrospective Studies; Transcription Factors

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 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 BRCA1/2 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 BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 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 to 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 (P = .002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, 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 BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 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 BRCA1/2 mutation.