Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to risk of different breast cancer subgroups: a Malmo Diet and Cancer Study

Thyroid hormone level has been positively associated with breast cancer risk and with breast cancer cell proliferation and growth. Although breast cancer is a heterogeneous disease, this is the first study assessing pre-diagnostic levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibodies (TPO-Ab) in relation to breast cancer subgroups and aggressiveness. The Malmo Diet and Cancer Study collected blood samples from 17,035 women between 1991 and 1996. Free T3, free T4, TSH, and TPO-Ab were analyzed in 676 incident breast cancer cases and 680 controls. Breast tumors were classified according to tumor size, axillary lymph node involvement, histological grade, histological type, hormone receptor status (ER, PgR), as well as Ki67, cyclin D1, and p27. Odds ratios of different breast cancer subgroups were calculated using a logistic regression analysis adjusted for potential confounders. High fT4 was associated with a statistically significant higher risk of overall breast cancer, small, grade I, ER-positive, PgR-positive, and cyclin D1 low tumors. The associations for ER and PgR were verified in a heterogeneity analysis. Low TPO-Ab was associated with a higher risk of overall breast cancer, ductal, large, ER-positive, PgR-positive, cyclin D1 low, and p27 high tumors. The heterogeneity analysis verified the association for tumor size. Free T3 was not associated with overall breast cancer risk, but in the heterogeneity analysis, high fT3 was associated with tumor size and expression of p27. There were no strong associations between TSH and overall breast cancer risk or any tumor subgroup. High pre-diagnostic fT4 levels and low pre-diagnostic TPO-Ab levels were associated with an increased risk of breast cancer. This increase was mainly limited to a higher incidence rate of less aggressive breast cancer subgroups.