The association between serum folate and folate sub‐species with overall survival after breast cancer diagnosis

Abstract

We studied the relationship between total serum folate and folate sub‐species, 5‐methyltetrahydrofolic acid (5MTHF), 5‐formyltetrahydrofolic acid (FOTS), pteroylglutamic acid (PGAS) and tetrahydrofolic acid (THFS) with overall survival after breast cancer diagnosis. Participants were post‐menopausal women diagnosed with breast cancer (n = 498) between 1994–1995 with a mean follow‐up of 80 months. Total serum folate and subspecies samples collected at or post diagnosis were measured by radio protein binding assay, and by isotope‐dilution LC/MS/MS methodology, respectively. In the Cox proportional multivariate hazards models [controlled for disease stage, age at diagnosis, body mass index (BMI), parity, ER/PR status, alcohol use and energy intake], we found that the relative risk of dying in the highest quartile for total serum folate levels was nearly 50% lower (RR: 0.56, 95% CI: 0.32–0.99) compared with all other groups (1st, 2nd and 3rd quartile). There was a borderline significant reduced risk of dying in the highest quartile of THFS, the bioactive form of folate, (RR: 0.61, 95% CI: 0.34–1.07) compared with the other quartiles. These results suggest that total folate concentrations at and/or after diagnosis were positively associated with survival after breast cancer diagnosis, and that of the folate sub‐species that contribute to total circulating folate levels, only THFS was associated with reduced risk of dying after breast cancer diagnosis, which has implications for dietary and supplemental folate intake recommendations.