TPOAb and Thyroid Function Are Not Associated with Breast Cancer Outcome : Evidence from a Large-Scale Study Using Data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001)

Background: Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. Objectives: We aimed to clarify this association in a large cohort using the phase-III randomized controlled “Taxotere as Adjuvant Chemotherapy Trial” (TACT, CRUK01/001). Methods: TACT women >18-years-old with node-positive or high risk nodenegative early breast cancer (pT1-3a,pN0-1,M0), with stored plasma (n=1974), taken 15.5 [7.0-24.0] months (median [IQR]) after breast surgery were studied. Patients had also received chemotherapy (100%), radiotherapy (1745/1974 [88.4%]), hormonal therapy (1378/1974 [69.8%]), or trastuzumab (48/1974 [2.4%]). History of thyroid diseases and/or related treatments was not available. The prognostic significance of autoantibodies to thyroid peroxidase (TPOAb; positive ≥6 kIU/L), free-thyroxine and thyrotropin (combined: euthyroid, hypothyroid, hyperthyroid) was evaluated for disease-free survival (DFS), overall-survival (OS), time-to-recurrence (TTR), with Cox regression models in univariate and multivariable analyses. The extended median follow-up was 97.5 months. Results: No difference in DFS was found by TPOAb status (unadjusted-hazard ratio [HR]: 0.97, 95%CI: 0.78-1.19, P=0.75) and/or thyroid function (unadjusted-HR [hypothyroid versus euthyroid]: 1.15, 95%CI: 0.79-1.68, P=0.46; unadjusted-HR [hyperthyroid versus euthyroid]: 1.14, 95%CI: 0.82-1.61, P=0.44). Similar results were obtained for OS, TTR, multivariable analyses, when TPOAb titre by tertiles was considered and in a subgroup of 123 patients with plasma collected before adjuvant treatments. Conclusions: No evidence for a prognostic role of TPOAb and/or thyroid function in moderate-high risk early breast cancer was found in the largest and longest observational study to date.