Abstract LB-5: Ultraviolet radiation inhibits murine mammary carcinogenesis at an early stage

Abstract

Abstract Epidemiological studies of geographical variations in breast cancer mortality rates have found increased death rates at higher latitudes in USA and other countries. This breast cancer latitudinal gradient is hypothesized to be mediated by ultraviolet radiation (UVR) - produced vitamin D3. We have tested the effects of UVR in the well-described C3(1)/Tag transgenic mouse and have demonstrated that UVR started at age 6w and continued throughout the life of the mouse inhibits mammary carcinogenesis. Thus UVR prolongs palpable tumor - free survival (15±0.9 vs. 18±1.1 w; p=0.023) and delays the time of death (22±0.9 vs. 25±1.1 w; p=0.028). To differentiate between an inhibitory effect of UVR on the processes leading to initial histologic changes vs. an effect on the later stage of progression from microscopic to palpable tumors we assessed the anti-carcinogenic effects of UVR given at different time points and for different intervals. UVR was given thrice weekly at 350mJ/cm2 per treatment to FVBN/J C3(1)-Tag females. Treatment groups: (1) No UVR, (2) UVR age 6 w until end of the study, (3) UVR age 6 w until the 1st palpable tumor, (4) UVR 1st palpable tumor until the end of the study, (5) UVR age 12 w (a time when histologic changes are present but no tumor has become palpable) until the 1st palpable tumor. Results: (1) UVR significantly delayed the onset of the first palpable tumor when started at age 6 w (12 days delay, p=0.005, two-tailed t-test) but not when started at age 12 w. (2) UVR started after the 1st tumor became palpable did not reverse already-existing histological changes and did not prolong overall survival, thus confirming that UVR's effects occur at an early, pre-palpable stage of carcinogenesis. (3) UVR was sufficient to delay the first palpable tumor and to prolong overall survival (21±1.0 vs. 23±0.9 w; p=0.002, compared to untreated group) even at short-term exposure from age 6 w until the 1st palpable tumor. Furthermore, UVR reduces the percentage of glands with DCIS changes appreciable histologically by 82, 55, 66, 20 and 19% at ages 9, 11, 13, 14 and 15 weeks). Thus UVR is able to delay the appearance of early stages of breast carcinogenesis but is unable to reverse already-present histologic changes and their progression to more advanced cancer. Garland, F. C. et all. Prev Med 1990, 19, 614-22.; Green, J. E. et all. Oncogene 2000, 19, 1020-7. Citation Format: Anastasia M. Makarova, Grace Wang, Eileen Libove, Yefim Khaimskiy, Ervin H. Epstein. Ultraviolet radiation inhibits murine mammary carcinogenesis at an early stage. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-5. doi:10.1158/1538-7445.AM2014-LB-5