Breast Cancer Radiotherapy: Safe for All?

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.23.4000 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11099332 Breast Cancer Radiotherapy: Safe for All? Jaya UnnithianxJaya UnnithianSearch for articles by this author , Roger MacklisxRoger MacklisSearch for articles by this author Bruce G. HafftyxBruce G. HafftySearch for articles by this author Show More The Cleveland Clinic Foundation Cleveland, OHYale University School of Medicine New Haven, CT https://doi.org/10.1200/JCO.2000.18.23.4000 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01122000In Reply:Drs Unnithian and Macklis bring out some important cautionary notes in the interpretation of our recent study comparing breast cancer patients with second malignancies undergoing lumpectomy and radiation with a similar cohort undergoing surgical therapy alone.1 Caveats in the interpretation of our data include, at the least, the heterogeneity of the population, the lack of a randomized control population and its inherent selection biases, and the limited number of patients at risk for more than 10 to 15 years, when radiation-induced malignancies are likely to occur.Clearly, our study would not have the power, nor adequate information, to detect excess radiation-induced malignancies among subsets of patients with germline mutations in BRCA1/BRCA2, A-T, P53, or other genes associated with radiation repair or radiation response. However, I would emphasize the need to differentiate those patients with a family history of breast cancer from patients with a documented deleterious mutation in BRCA1/BRCA2, P53, or A-T, with respect to the possibility of an increased risk of radiation-induced malignancies.I concur with Unnithian and Macklis that patients with a genetic predisposition to breast cancer represent a separate risk group with respect to contralateral disease. Breast cancer patients with deleterious mutations in BRCA1 or BRCA2 have an estimated risk of subsequently developing contralateral breast cancer ranging from 40% to 70%.2 Whether the scattered dose from breast or chest wall irradiation or even low doses from routine mammography potentiate this risk is a currently unanswered question worthy of further investigation.Fortunately, patients with inherited deleterious mutations in BRCA1/BRCA2, P53, A-T, or other genes associated with radiation repair or radiation response represent a minority (5% to 10%) of patients with breast cancer. Further studies are clearly warranted, and substantial limitations in our own study and the currently available literature must be acknowledged. However, the comparable second malignancy rate in irradiated and nonirradiated breast cancer patients provides additional information to clinicians and patients regarding the potential risks and benefits of breast-conserving therapy for the vast majority of patients with early-stage breast cancer.1. Obedian E, Fisher DB, Haffty BG: Second malignancies after treatment of early-stage breast cancer: Lumpectomy and radiation therapy versus mastectomy. J Clin Oncol 18:: 2406,2000-2412, Link, Google Scholar2. Ford D, Easton DF, Bishop DT, et al: Risks of cancer in BRCA1-mutation carriers: Breast Cancer Linkage Consortium. Lancet 343:: 692,1994-695, Crossref, Medline, Google Scholar