Abstract P3-08-01: Gamma-ray induced mutagen sensitivity and overall survival in young women with breast cancer

Background: Hypersensitivity to radiation has been shown to be a risk factor for the development of breast cancer. We aim to determine whether the same hypersensitivity predicts for adverse clinical outcomes in patients diagnosed with carcinoma of the breast. Methods: 465 young, female, non-Hispanic white patients diagnosed with carcinoma of the breast at our institution from 1/1997 to 12/2005 were included in this study. All cases were histologically confirmed and all blood was drawn prior to any systemic or local therapy. Patient age, body mass index (BMI), menopause status, tumor laterality, AJCC stage, ER status, nuclear grade, and receipt of chemotherapy and radiation were extracted from patient medical records. A gamma-ray-induced mutagen sensitivity assay was performed using standard published methods to evaluate individual responses to radiation. The number of simple chromatid breaks per sample was counted from 50 well-spread metaphases. Each simple chromatid break was counted as a single break and each isochromatid break, exchange figure, or interstitial deletion as two breaks. The mean value of chromatid breaks per cell (b/c) was then calculated and recorded. Cox multivariable proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between b/c and overall survival. Results: A total of 402 patients had a b/c value recorded and were included in the final analysis. The patient median age was 46 years (range 22-55). 341 patients (84.8%) had invasive cancer and 253 patients (69.9%) had ER+ disease. AJCC stage distribution was stage 0 (15.2%), stage 1 (41.5%), stage 2 (33.5%), stage 3 (9.5%) and stage 4 (0.3%). The median follow-up for all patients was 97.2 months (interquartile range, IQR 83.3-119.6 months). The median b/c was 0.5 (IQR 0.38-0.62). The 5 and 10-year survival for all patients was 92.6% and 87.5%. A statistically significant decrease in 5 and 10-year overall survival was seen in patients with b/c greater than the median value of 0.5 (96.2% vs. 89.2%, p=.007 and 90.8% vs. 84.5%, p=.046, respectively). On multivariable analysis (MVA), age at diagnosis (HR 0.95, CI 0.91-0.99, p=.017), BMI (HR 1.07, CI 1.03-1.12, p=.003), ER status (HR= 0.31, CI 0.16-0.61, p=.01), AJCC stage (HR 1.91, CI 1.2-3.0, p=.006), and b/c level (HR 5.67, CI 1.5-18.2, p=.01) all predicted for overall survival. Excluding the 61 patients with in situ disease, there remains a significant difference in survival at both 5 and 7 years (95.5% vs. 88.5%, p=.017 and 93.5% vs. 86%, p=.021). A trend for decrease survival was seen at 10 years (p=0.09). On MVA for patients with invasive disease, age at diagnosis (HR=0.95, 95% CI 0.91-0.99, p=.026), BMI (HR=1.06, 95% CI 1.01-1.11, p=.023), AJCC stage (HR=2.41, CI 1.51-3.91, p=.0003), and ER status (HR=0.25, CI 0.12-0.49, p Conclusions: In this cohort of young, female, non-Hispanic white breast cancer patients, a greater b/c level predicted for decreased overall survival. The use of a gamma-ray-induced mutagen sensitivity assay may be prognostic and help select for those at increased risk of death. Citation Format: Michael C Stauder, Simona F Shaitelman, Pamela K Allen, Abenaa M Brewster, Banu K Arun, Wendy A Woodward, Thomas A Buchholz, Li-E Wang. Gamma-ray induced mutagen sensitivity and overall survival in young women with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-08-01.