Aurelia Vattai1, Elif Akyol1, Christina Kuhn1, Simone Hofmann1, Helene Heidegger1, Franz von Koch2, Kerstin Hermelink1, Rachel Wuerstlein1, Nadia Harbeck1, Doris Mayr3, Christine Spitzweg4, Bettina Toth5, Sven Mahner1, Udo Jeschke6, Nina Ditsch1. 1. Department of Gynaecology and Obstetrics, Breast Center, Ludwig-Maximilians University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. 2. Department of Obstetrics and Gynaecology, Klinikum Dritter Orden, Menzinger Str. 44, 80638, Munich, Germany. 3. Department of Pathology, Ludwig-Maximilians University of Munich, Thalkirchner Str. 142, 81337, Munich, Germany. 4. Department of Internal Medicine, Ludwig-Maximilians University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. 5. Department of Gynaecological Endocrinology and Reproductive Medicine, University Hospital Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. 6. Department of Gynaecology and Obstetrics, Breast Center, Ludwig-Maximilians University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. Udo.Jeschke@med.uni-muenchen.de.
Abstract
PURPOSE: A correlation between breast cancer and thyroid disorders has been described in previous studies. Degraded thyroid hormones are referred to as trace amines. These endogenous amines have the ability to bind to the G-protein-coupled receptor TAAR1 (trace amine-associated receptor) and thereby activate it. TAAR1 is able to modulate the serotonergic and dopaminergic system in the brain and has so far been studied in the neurological field. The following study represents the first investigation of the regulation of TAAR1 in primary breast cancer (no metastases, M0). METHODS: Immunohistochemical analyses were carried out to detect TAAR1 expression in formalin fixed paraffin embedded breast cancer samples. Survival times of primary breast cancer patients (M0) with and without TAAR1 expression in their tumours were compared by Kaplan-Meier curves, and correlations between ordinal variables were determined with Spearman's rank correlation coefficient. RESULTS: The investigation showed a correlation between TAAR1 expression and tumour differentiation grade. A well differentiated tumour grade (G1) was associated with higher TAAR1 expression and HER2 and HER4 positivity predicted higher TAAR1 expression. A TAAR1 overexpression (IRS ≥ 6) was associated with significantly longer overall survival (OS) (p = 0.02) than that of reduced TAAR1 expression (IRS < 6) during a maximum follow-up of 14 years, demonstrating that TAAR1 has a favourable effect on OS of early breast cancer patients. CONCLUSIONS: We conclude that TAAR1 seems to be an independent predictor for breast cancer survival. Modulation of TAAR1 may represent a novel targeting strategy for breast cancer prevention and therapy.
PURPOSE: A correlation between breast cancer and thyroid disorders has been described in previous studies. Degraded thyroid hormones are referred to as trace amines. These endogenous amines have the ability to bind to the G-protein-coupled receptor TAAR1 (trace amine-associated receptor) and thereby activate it. TAAR1 is able to modulate the serotonergic and dopaminergic system in the brain and has so far been studied in the neurological field. The following study represents the first investigation of the regulation of TAAR1 in primary breast cancer (no metastases, M0). METHODS: Immunohistochemical analyses were carried out to detect TAAR1 expression in formalin fixed paraffin embedded breast cancer samples. Survival times of primary breast cancerpatients (M0) with and without TAAR1 expression in their tumours were compared by Kaplan-Meier curves, and correlations between ordinal variables were determined with Spearman's rank correlation coefficient. RESULTS: The investigation showed a correlation between TAAR1 expression and tumour differentiation grade. A well differentiated tumour grade (G1) was associated with higher TAAR1 expression and HER2 and HER4 positivity predicted higher TAAR1 expression. A TAAR1 overexpression (IRS ≥ 6) was associated with significantly longer overall survival (OS) (p = 0.02) than that of reduced TAAR1 expression (IRS < 6) during a maximum follow-up of 14 years, demonstrating that TAAR1 has a favourable effect on OS of early breast cancerpatients. CONCLUSIONS: We conclude that TAAR1 seems to be an independent predictor for breast cancer survival. Modulation of TAAR1 may represent a novel targeting strategy for breast cancer prevention and therapy.
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