Abstract LB-460: Effects of folic acid supplementation on mammary tumor progression

Abstract

Abstract Background: The role of folate in breast cancer is highly controversial. Although some epidemiologic studies have suggested a protective effect of high folate status on breast cancer risk, recent studies have suggested that high folate intake, largely from folic acid (the synthetic form of folate), and high plasma folate levels may increase breast cancer risk. In animal studies, folic acid supplementation was shown to promote the progression of established preneoplastic lesions of colon cancer. Folic acid intake in North America has drastically increased over the past decade due to folic acid fortification and widespread supplemental use. Almost 70% of breast cancer patients consume folic acid containing vitamin supplements after diagnosis. The benefits of folic acid supplementation in patients with breast cancer are unknown and there is a concern that folic acid supplementation may in fact adversely affect breast cancer progression. We therefore investigated the effects of folic acid supplementation on the progression of established mammary tumors in the DMBA rat model. Methods: Female Sprague Dawley rats were placed on a control diet containing 2 mg folic acid/kg diet and mammary tumors were initiated with DMBA at 7 weeks of age. When the sentinel tumor reached a diameter between 7–9 mm, rats were randomized to receive a diet containing 2 (control), 5, 8, or 10 mg of folic acid/kg diet for up to 12 weeks. Body weight and mammary tumor growth were measured weekly and plasma folate levels at necropsy were determined. At necropsy, the sentinel and all other mammary tumors were excised and histologically analyzed. Results: The final weight of the animals at necropsy was not significantly different among the 4 groups. Animals on the control and 10 mg folic acid/kg diet had significantly faster weight gain than those on the 8 mg folic acid/kg diet (p<0.02) while those on the 5 mg folic acid diet did not differ significantly from either group. Plasma folate levels significantly reflected the supplemental levels of folic acid in a dose-responsive manner (p<0.05). Sentinel tumor growth (mm2/week) was not significantly different among the 4 groups at 4, 7, and 12 post randomization. Sentinel tumor weight at necropsy was lower in the control group compared with the 5 and 8 (p<0.05) and with the 10 (p=0.051) mg folic acid/kg diet groups. Total weight of all mammary tumors was highest in 5 and 8 mg supplemented groups compared to the control group (p< 0.05, p=0.086). Conclusion: Our data suggest that folic acid supplementation may promote the progression of established mammary tumors, although no clear dose-responsive relationship was observed. Given the drastically increased folic acid intake and the mortality and morbidity of breast cancer in North America, the potential adverse effect of folic acid supplementation on breast cancer progression needs to be clarified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-460. doi:10.1158/1538-7445.AM2011-LB-460