Benjamin Nisman1, Tanir M Allweis2,3, Einat Carmon4, Luna Kadouri5,3, Bella Maly6, Ofra Maimon5, Amichay Meirovitz5, Tamar Peretz5,3. 1. Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel; nisman@hadassah.org.il. 2. Department of Surgery and Breast Health Center, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel. 3. Faculty of Medicine, Hebrew University, Jerusalem, Israel. 4. Departmentt of Surgery, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel. 5. Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel. 6. Department of Pathology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel.
Abstract
BACKGROUND/AIM: Thyroid hormones (THs) stimulate breast cancer (BC) cell proliferation. We hypothesized that these hormones and the proliferative marker thymidine kinase 1 (TK1) represent the initial and final steps of the proliferative pathway, respectively. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum TK1 activity, in 144 newly diagnosed BC patients, and examined the associations between THs and proliferation in different BC receptor profiles. RESULTS: TK1 activity did not correlate with TSH (r=0.06, p=0.473) or FT4 levels (r=0.04, p=0.665), but did correlate with FT3 levels (r=0.28, p=0.001). Elevated FT3 (>6.0 pmol/l) predicted increased TK1 activity (>140 Du/l) after adjusting for age (odds ratio 4.1, p=0.014). We also found a significant association of the combined elevation of FT3 and TK1, assumed as a surrogate marker of accomplished proliferative signal, with triple-negative (TN) profile (p=0.003). The rates of combined FT3 and TK1 elevation in TN and ER-positive profiles were 20.0% and 1.8%, respectively (p=0.005). CONCLUSION: FT3 may be involved in proliferative signaling, as measured by TK1 activity, predominately in TN breast cancer.
BACKGROUND/AIM: Thyroid hormones (THs) stimulate breast cancer (BC) cell proliferation. We hypothesized that these hormones and the proliferative marker thymidine kinase 1 (TK1) represent the initial and final steps of the proliferative pathway, respectively. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum TK1 activity, in 144 newly diagnosed BC patients, and examined the associations between THs and proliferation in different BC receptor profiles. RESULTS:TK1 activity did not correlate with TSH (r=0.06, p=0.473) or FT4 levels (r=0.04, p=0.665), but did correlate with FT3 levels (r=0.28, p=0.001). Elevated FT3 (>6.0 pmol/l) predicted increased TK1 activity (>140 Du/l) after adjusting for age (odds ratio 4.1, p=0.014). We also found a significant association of the combined elevation of FT3 and TK1, assumed as a surrogate marker of accomplished proliferative signal, with triple-negative (TN) profile (p=0.003). The rates of combined FT3 and TK1 elevation in TN and ER-positive profiles were 20.0% and 1.8%, respectively (p=0.005). CONCLUSION: FT3 may be involved in proliferative signaling, as measured by TK1 activity, predominately in TN breast cancer.