The Association Between Circulating Total Folate and Folate Vitamers With Overall Survival After Postmenopausal Breast Cancer Diagnosis

Abstract

We studied the relationship between plasma total folate and folate vitamer concentrations [5-methyltetrahydrofolic acid, pteroylglutamic acid (folic acid) and tetrahydrofolic acid] with overall survival after breast cancer diagnosis. A secondary aim was to assess the relationship between folic acid supplement use with circulating total folate and folate vitamer concentrations. Participants were postmenopausal women diagnosed with breast cancer (n = 498) with an average follow-up of 6.7 yr. Plasma total folate and folate vitamers were measured by isotope-dilution LC-MS/MS in samples collected at or postdiagnosis. Cox proportional multivariate hazards models (controlled for stage, age at diagnosis, body mass index, parity, hormone replacement therapy use, treatment, alcohol use, folic acid use, and energy intake), were used to assess overall survival after breast cancer diagnosis. We found that the relative risk of dying for women with plasma total folate concentrations in the highest quartile was 59% lower (hazard ratio: 0.41, 95% confidence interval: 0.19–0.90) compared with the lowest quartile. Data on supplement use showed that women taking folic acid supplements had significantly higher circulating total folate and folate vitamer concentrations (P < 0.0001), suggesting that increased folate consumption through diet and/or supplementation may improve prognosis after breast cancer diagnosis.

ACKNOWLEDGMENTS

We would like to thank Melinda Verissimo for providing technical assistance and support in manuscript preparation and submission. The findings and conclusions in this report are those of the authors and do not necessarily represent the official views or positions of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry, the National Institutes of Health, or the Department of Health and Human Services.

FUNDING

The present study was supported by the National Cancer Institute, NIH grant, 5K07CA101964.