A new study recently presented at the annual American Association for Cancer Research (AACR) Meeting in Washington, D.C. has reported that vitamin A can inhibit or promote the formation and metastasis of breast cancer according to the functional status of retinoic acid receptor alpha in the cells. Preformed vitamin A, or retinol, is found in animal foods such as liver and whole milk, and in some fortified processed foods. Certain carotenoids such as beta-carotene are also efficiently converted into retinol. Once retinol is in turn converted into its bioactive form, retinoic acid, it plays important roles in cell division, cell death, and cell differentiation. In the study, retinoic acid was found to regulate a network of tumor suppressor genes governing cell death, proliferation, differentiation, migration, and invasion through retinoic acid receptor alpha.

Retinoic acid was found to exert a double-edged action: it either inhibited or promoted the formation of cancer according to the functional status of one of its receptors, retinoic acid receptor alpha. To perform the investigation, athymic female nude mice were implanted with subcutaneous xenograft tumors consisting of one of two clonal lines of estrogen receptor alpha positive (ERα+) T47D breast cancer cells: one with a functional retinoic acid receptor alpha-regulated gene network (T47DLXC5) and one without functional retinoic acid receptor alpha (T47DDNC8). The mice were administered a diet with either retinoic acid or retinol for six weeks. Retinoic acid was found capable of exerting a clear tumor-promoting action due to the loss or functional inhibition of retinoic acid receptor alpha. Both diets were found stimulate T47DDNC8 xenograft tumors to grow and metastasize to distant sites, whereas the growth of T47DLXC5 xenograft tumors was inhibited and the cells did not become invasive. In breast cancer, retinoic acid receptor alpha function often is impaired due to a variety of upstream causes, including loss of ERα, an important retinoic acid receptor alpha transcriptional regulator. This raises the possibility that dietary sources of vitamin A can also promote breast cancer development in cells with impaired retinoic acid receptor alpha.

Implications of the study

Consumption of vitamin A as part of the diet has been observed to reduce the risk of various cancers. However, studies of vitamin A and beta-carotene supplements have not had favorable results, most famously in the case of lung cancer. In one major study, approximately 18,000 men and women who were smokers, former smokers, or workers exposed to asbestos were randomly assigned to take daily supplements of beta-carotene or vitamin A. Unexpectedly, the risk of lung cancer was found to be 16% higher among participants taking either supplement compared to those taking a placebo after a six-year follow-up period.

Previous studies investigating the associations between levels of retinol, beta-carotene and other carotenoids in the blood and the risk of breast cancer have fairly consistently reported a benefit for high versus low levels. However, some previous studies have also found that estrogen receptor negative (ER-) breast cancer cells do not respond at all or not as favorably to retinol and related compounds. According to the study above, this could be because some ER- breast cancer cells have lost retinoic acid receptor alpha functionality.

Bottom line: We do not recommend taking vitamin A, beta-carotene, lycopene or other supplements to prevent breast cancer, or during or after treatment for breast cancer. High-carotenoid foods are for the most part not recommended during radiation and chemotherapy (see the related web pages for lists of recommended foods). Survivors of estrogen receptor negative (ER-/PR-, ER-/PR+) breast cancer should emphasize the foods that have been shown to inhibit their breast cancer types (which for the most part do not include high levels of carotenoids). On the other hand, since carotenoid-containing foods have been shown to reduce the risk of estrogen receptor positive (ER+/PR+, ER+/PR-) breast cancer and improve survival, they should be a significant part of the diet of women at high risk for breast cancer (since most breast cancer is ER+) and survivors of ER+ breast cancer.