Abstract 3330: Genomic profiling of breast cancers in women with protracted exposure to low doses of radiation from the 1986 Chernobyl nuclear accident
Authors: Guenthoer Jamie , Onstad Lynn , Chai Xiaoyu , Rivkind Nikolai B. , Kurnasova Irina V. , Troshin Vladislav P. , Makarova Margarita , Korchagina Elena A. , Stepanenko Valeriy F. , Beluhka Irina , Kulikov Sergei M. , Shklovsky-Kordi Nikita E. , Hsu Li , Voillequé Paul , Kopecky Kenneth J. , Davis Scott , Porter Peggy L. 
Published: August 2015

Abstract
Exposure to ionizing radiation is one of the only known environmental causes of breast cancer, but most evidence for this relationship is derived from studies of high-dose exposures delivered at high-dose rates. Radiation exposure at low doses protracted over time is a more common pattern, yet the association of such exposure with breast cancer risk is understudied. In a population-based case-control study of women living in Bryansk Oblast, Russia, exposed to relatively low-doses of radiation from the 1986 Chernobyl nuclear accident over about 20 - 30 years, we characterized 468 breast cancer patients (25 - 55 years old, mean = 46.7 years). Preliminary estimates of individual radiation doses to the breast from internal and external exposure to Chernobyl fallout ranged from 0.1 mGy to 279 mGy (mean = 6.8 mGy, median = 1.1 mGy). The majority of the breast cancer patients in this cohort had node-positive disease (60%), were ER/PR positive (77% and 67% respectively) and HER2 negative (74%). We performed global profiling of gene expression using the Illumina WG-DASL assay on 442 tumors and defined their intrinsic subtypes (Hu Z, et al., 2003). Among those tumors, 22% were Basal-like, 11% Her2-enriched, 30% Luminal A, 20% Luminal B, and 17% Normal-breast-like. We compared gene expression between the quartile of patients with the highest individual doses (N = 109, mean = 23.7 mGy, median = 16.5 mGy) and the lowest (N = 109, mean and median = 0.5 mGy) and identified genes differentially expressed between the groups. Although there is evidence in the literature from studies of women exposed to high doses of radiation at high-dose rates that suggests a positive association between basal-like cancer and radiation exposure, our preliminary analyses found a higher rate of basal-like cancers in the low exposure group (26.9%) compared with the high exposure group (19.2%). Triple negative cancers identified by IHC were also more common in the low than in the high exposure group (17.0% vs. 6.7%), though neither of these trends was significant. EGFR expression, a marker of basal-like cancers, was seen in 17.7% of tumors in patients with low exposure compared with 7.4% in the high exposure group (p = 0.07). Further, studies suggest radiation exposure prior to puberty is associated with specific tumor marker expression. In our study, 14.4% of the patients were prepubescent at the time of the Chernobyl accident (ATA). We observed a statistically significant association between Her2 and pubescence: patients who were prepubescent ATA were more likely to have Her2-positive tumors than those who were not prepubescent (40% vs 24%, p = 0.007). This unique study of a large cohort of women with protracted exposure to low doses of radiation provides one of the first opportunities to assess the effect of such exposure on the molecular characteristics of breast tumors.
Citation Format: Jamie Guenthoer, Lynn Onstad, Xiaoyu Chai, Nikolai B. Rivkind, Irina V. Kurnasova, Vladislav P. Troshin, Margarita Makarova, Elena A. Korchagina, Valeriy F. Stepanenko, Irina Beluhka, Sergei M. Kulikov, Nikita E. Shklovsky-Kordi, Li Hsu, Paul Voillequé, Kenneth J. Kopecky, Scott Davis, Peggy L. Porter. Genomic profiling of breast cancers in women with protracted exposure to low doses of radiation from the 1986 Chernobyl nuclear accident. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3330. doi:10.1158/1538-7445.AM2015-3330