Abstract 3056: Mitochondrial DNA copy number and risk of second primary tumors in long-term breast cancer survivors

Abstract

Abstract Background. Mitochondria is constantly exposed to reactive oxygen species (ROS), an important factor in carcinogenesis. Altered mitochondrial DNA (mtDNA) copy number in peripheral blood has been associated with increased risks of several cancers, including breast cancer. However, the association of mtDNA copy number with clinical outcomes of breast cancer has not been reported. This study aimed to assess the association of mtDNA copy number with second primary tumors (SPT) in long-term breast cancer survivors. Methods. We measured mtDNA by quantitative PCR in patients in 68 long-term breast cancer survivors with SPT, 100 long-term breast cancer survivors without SPT and 97 newly diagnosed breast cancer cases. Cases with and without SPT were matched by years since diagnosis, age at time of sample collection and race. Differences between mtDNA copy number among groups were analyzed using the Wilcoxon rank sum test. Results. MtDNA copy number was significantly higher in long-term breast cancer survivors (either with SPT or not SPT) compared with newly diagnosed breast cancer patients (Mean (SD), 1.03 ± 0.25 vs 0.95 ± 0.27; p = 0.005). We did not observe significant differences of mtDNA copy number between long-term survivors with SPT and without SPT. However, in stratified analyses by epidemiological and clinical variables, we observed lower mtDNA copy number in HER2-positive long-term survivors with SPT than those without SPT (0.84 ± 0.13 vs 1.27 ± 0.44; p = 0.010) and in pre-menopause long-term survivors with SPT than those without SPT (0.95 ± 0.20 vs 1.06 ± 0.22; p = 0.034). A borderline significance of mtDNA copy number between SPT and non-SPT ER-negative long-term survivors was also noted (0.90 ± 0.17 vs 1.18 ± 0.41, p = 0.056). Conclusion. Higher mtDNA copy number was found in long-term breast cancer survivors compared to newly diagnosed cases. There were significant associations between lower mtDNA copy number and SPT in long-term breast cancer survivors who are HER2+ or are pre-menopause. These results indicate a role of mtDNA copy number in long-term breast cancer survivorship. Citation Format: Miguel Santibanez, Alma Rodriguez, Michelle A. Hildebrandt, David W. Chang, Xifeng Wu. Mitochondrial DNA copy number and risk of second primary tumors in long-term breast cancer survivors. [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 3056. doi:10.1158/1538-7445.AM2015-3056