Potential prognostic value of the free T3/T4 ratio in HR+/HER2 − metastatic breast cancer treated with CDK4/6 inhibitors

The free triiodothyronine (fT3)/free thyroxine (fT4) ratio is an index estimating the peripheral activity of thyroid hormones. The prognostic role of the fT3/fT4 ratio in colorectal cancer, urothelial cancer, renal carcinoma, and lymphoma is well-recognized, but its effect in metastatic breast cancer remains unestablished. We conducted a retrospective study of metastatic breast cancer patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors at Hacettepe University Hospital. Baseline fT3 and fT4 levels were recorded, and patients were categorized into two groups based on the median fT3/fT4 ratio: Low and High fT3/fT4 Ratio Groups. We included 162 h-positive/HER2-negative metastatic breast cancer patients. There were no significant differences between the Low and High fT3/fT4 Ratio Groups in terms of age, sex, tumor grade, histopathologic type, menopausal status, sites of metastases, lines of treatment prior to CDK4/6 inhibitors, type of CDK4/6 inhibitor, or endocrine backbone therapy. Of all patients, 47 (29.2%) received two or more lines of treatment before initiating CDK4/6 inhibitors. High fT3/fT4 ratios were associated with significantly longer progression-free survival (PFS) compared to Low fT3/fT4 ratios (median, 9.7 vs. 6.9 months; HR: 0.68; 95% CI: 0.47–0.97; p = 0.035) and significantly longer overall survival (OS) compared to Low fT3/fT4 ratios (median, NR vs. NR months; HR: 0.30; 95% CI: 0.15–0.60; p < 0.001). Our study showed that high fT3/fT4 ratios were independent factors associated with longer PFS and OS in metastatic breast cancer patients treated with CDK4/6 inhibitors, supporting the role of high fT3/fT4 ratios as a prognostic marker.