SPECIAL DEPARTMENTS
Authors: Silvia C. Formenti, Susan Preston-Martin, Bruce G. Haffty
Journal: Journal of Clinical Oncology (2000)

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.2000.18.5.1159 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10694571 Silvia C. FormentixSilvia C. FormentiSearch for articles by this author , Susan Preston-MartinxSusan Preston-MartinSearch for articles by this author Bruce G. HafftyxBruce G. HafftySearch for articles by this author Show More Kenneth Norris Jr Comprehensive Cancer Center University of Southern California Keck School of Medicine Los AngelesCAYale University School of Medicine New HavenCT https://doi.org/10.1200/JCO.2000.18.5.1159 Full Text PDF Figures and Tables "." Journal of Clinical Oncology, 18(5), p. 1159© 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01032000In Reply:The letter from Drs Formenti and Preston-Martin pose some interesting questions regarding radiosensitivity/radioresistance in patients with BRCA1/2 germline mutations. I would interpret our preliminary studies recently published in the Journal of Clinical Oncology as suggesting that patients with germline BRCA1/2 mutations who undergo breast-conserving therapy may, due to their underlying predisposition to develop breast cancer, have an elevated risk of developing second primary tumors in the residual breast tissue.1 As pointed out in our detailed analysis of each of the BRCA1/2 patients with a local relapse, the timing, as well as the comparisons in location and histology, strongly suggests that these events do not represent “radioresistant” relapses but are more likely to be “de nouveau” second primary events. It seems that the risk of developing early “true recurrences” in this population is low and that breast cancers in BRCA1/2 carriers are at least as radiosensitive or, perhaps as some laboratory data suggest, more radiosensitive than sporadic breast cancers.Our previously published data cannot directly address the issue of radiation-induced malignancies raised in the letter by Formenti and Preston-Martin. Currently, we are collecting data on a larger cohort of conservatively treated patients with early-onset breast cancer who have a median follow-up of nearly 15 years. All of these patients are being tested for the BRCA1/2 mutation to assess the 10- to 15-year actuarial risk of ipsilateral and contralateral breast cancer events as a function of BRCA1/2 status. Although this study is not yet complete, my preliminary analysis seems to demonstrate that in BRCA1/2 carriers who underwent lumpectomy and radiation, the risk of ipsilateral and contralateral events runs a similar course, at least through 10 to 15 years. Furthermore, the long-term risk of contralateral events in these patients does not seem to differ substantially from the reported long-term risks of contralateral events in BRCA1/2 carriers who had undergone unilateral mastectomy (presumably without irradiation). Acknowledging the obvious caveats in interpreting the relatively limited available literature, these data suggest that therapeutic doses of irradiation have neither an adverse nor protective effect on the risk of second breast cancer events in patients with BRCA1/2 mutations, and there is no compelling evidence that indicates BRCA1/2 carriers differ from sporadic patients with respect to second malignancies “induced” by radiation. I agree with Formenti and Preston-Martin that this is an area worthy of investigation, but given the available literature, I see no immediate cause for concern regarding the appropriate clinical use of diagnostic and/or therapeutic doses of radiation in BRCA1/2 carriers. Currently, I approach the management of a patient with a germline BRCA1/2 mutation similar to that of a patient with sporadic breast cancer, but counsel these patients regarding the long-term risks of developing second breast malignancies. It remains to be determined whether hormonal manipulation with tamoxifen, oophorectomy, or other estrogen receptor modulators can modify these risks. It is hoped that future clinical and laboratory studies will help to better define the impact of BRCA1/2 status on the appropriate screening and local and systemic management of breast cancer.REFERENCE2. Turner BC, Harrold E, Matloff E, et al: germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: Implications for breast-conserving management in patients with mutations. J Clin Oncol 17::3017,1999-3024, BRCA1/BRCA2 BRCA1/BRCA2 Link, Google Scholar