Short Communication Effect of Mammography on Breast Cancer Risk in Women with Mutations in BRCA1 or BRCA2 Deborah Goldfrank, 1 Shannon Chuai, 2 Jonine L. Bernstein, 2 Teresa Ramon y Cajal, 3 Johanna B. Lee, 1 M. Carmen Alonso, 3 Orland Diez, 3 Monserrat Baiget, 3 Noah D. Kauff, 1 Kenneth Offit, 1 and Mark Robson 1 1 Clinical Genetics Service, Department of Medicine and 2 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York and 3 Hospital Sant Pau, Barcelona, Spain Abstract Women who carry mutations in either the BRCA1 or BRCA2 genes are at risk for early-onset breast cancer and are recommended to begin screening mammography at age 25 to 30 years. Results of in vitro and animal studies suggest that BRCA1/BRCA2 mutation carriers are hyper- sensitive to ionizing radiation and possibly to radiation- induced breast cancer. This study was undertaken to investigate the association of low-dose radiation exposure from mammograms with breast cancer status in BRCA mutation carriers. One hundred sixty-two female mutation carriers provided information at time of genetic testing about exposure to mammograms before enrollment. Using unconditional logistic regression, breast cancer status was not associated with number of mammograms received before diagnosis (affected women) or ascertainment [unaf- fected women; adjusted odds ratio (OR), 0.94; P = not significant]. A larger group of 213 women provided infor- mation about lifetime number of mammograms. There was no association between mammogram exposure and risk in the group as a whole (adjusted OR, 1.04; P = not significant), although there was a modest association in BRCA1 carriers (adjusted OR, 1.08; P = 0.03). These findings indicate that screening mammography is unlikely to be associated with a large increase in breast cancer risk in this population. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2311–3) Introduction Women carrying germ-line mutations in BRCA1 or BRCA2 are at risk for early-onset breast cancer (1). Such women currently receive annual mammograms beginning at age 25 to 30 years (2, 3). However, the benefits of mammography in very young women at hereditary risk are not defined and there are concerns that early mammography could increase the risk of cancer. Exposure to radiation has been shown to increase the risk of breast cancer in female atomic bomb survivors as well as in women receiving various forms of diagnostic and therapeutic X-ray exposure (4). BRCA1 and BRCA2 gene products are involved in the normal repair of DNA damage of the type caused by ionizing radiation, and BRCA -deficient cells are hypersensitive to radiation (5). Some studies have noted abnormalities in the DNA damage response in cells harboring a single mutated copy of BRCA1 or BRCA2 (1, 6-8), suggesting that radiation sensitivity may not require loss of both alleles. Other studies have not shown a phenotype associated with haploinsufficiency (9-11), and a clear connec- tion between in vitro radiosensitivity and a clinical predispo- sition to breast cancer from low-dose radiation exposure has not been established. To evaluate the possibility of such a connection, we examined the risk of breast cancer associated with mammogram exposure before genetic testing in women with deleterious BRCA mutations. Materials and Methods The subjects of this study are 213 BRCA mutation carriers identified at Memorial Sloan-Kettering Cancer Center (New York, NY) and at Hospital Sant Pau (Barcelona, Spain). All women received appropriate pretest genetic counseling and provided informed consent for testing. Before undergoing testing, women completed a baseline questionnaire, which included questions describing their participation in mammo- gramscreeningbeforeenrollment.AtMemorialSloan-Kettering Cancer Center, the questionnaire was administered as part of Institutional Review Board–approved follow-up studies of womenathereditaryriskconductedbetweenJanuary1995and December 2004. It included questions pertaining to the age at first mammogram, lifetime number of mammograms, and number of mammograms received in the preceding 12 months. Exposure before the diagnosis of breast cancer was calculatedbysubtractingthereportednumberofmammograms received in the year before enrollment from the lifetime total number of mammograms. This calculation was only done for women who completed the baseline questionnaire within 1 year of their breast cancer diagnosis. In Barcelona, the questionnaire was completed as part of the baseline clinical assessment between January 1996 and December 2004. Women directly reported the number of mammograms that they had received before diagnosis (if affected) or before enrollment (if unaffected). Postdiagnosis mammograms were not reported in Barcelona. Results The subjects of this report were all carriers of clearly deleterious mutations (121 BRCA1 and 92 BRCA2). The median age at ascertainment was 43 years (range, 25-73) 2311 Cancer Epidemiol Biomarkers Prev 2006;15(11). November 2006 Received 3/7/06; revised 7/18/06; accepted 8/21/06. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Mark Robson, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 212-434-5129; Fax: 212-434-5166. E-mail: robsonm@mskcc.org Copyright D 2006 American Association for Cancer Research. doi:10.1158/1055-9965.EPI-06-0176 Research. on October 26, 2016. © 2006 American Association for Cancer cebp.aacrjournals.org Downloaded from