The effect of non-oncology drugs on clinical and genomic risk in early luminal breast cancer

ESMO Open

article

B. Waissengrin¹  T. Zahavi³  M. Salmon-Divon³  A. Goldberg³  I. Wolf¹  T. Rubinek¹  T. Winkler⁴  O. Farkash¹  A. Grinshpun⁵  A. Zubkov⁶  M. Khatib⁷  S.S. Shachar¹  N. Keren¹  I. Carmi-Levy⁸  U. Ben-David²  A. Sonnenblick¹ 

[1] The Oncology Division, Tel Aviv Sourasky Medical Center;Sackler School of Medicine, Tel Aviv University;Department of Molecular Biology, Adelson School of Medicine, Ariel University;Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University;Breast Oncology Center, Department of Medical Oncology, Dana Farber Cancer Institute;Pathology Department, Pathology Institute, Tel Aviv Medical Center;Division of General Surgery, Tel Aviv Medical Center;Aummune Ltd

关键词: breast cancer;    estrogen receptor;    levothyroxine;    metformin;    Oncotype DX;    genomic risk;    clinical risk;   

DOI  :  10.1016/j.esmoop.2022.100648

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background An effect of non-oncology medications on cancer outcome has been proposed. In this study, we aimed to systematically examine the impact of commonly prescribed non-oncology drugs on clinical risk and on the genomic risk [based on the Oncotype DX recurrence score (RS)] in early breast cancer (BC).Experimental design We collected data on clinical risk (stage and grade), genomic risk (Oncotype DX RS), and on non-oncology medications administered to 1423 patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative BC during the month of their surgery. The influence of various medications on clinical and genomic risks was evaluated by statistical analysis.Results Out of the multiple drugs we examined, levothyroxine was significantly associated with a high Oncotype DX RS (mean 24.78; P < 0.0001) and metformin with a low Oncotype DX RS (mean 14.87; P < 0.01) compared with patients not receiving other non-oncology drugs (mean 18.7). By contrast, there were no differences in the clinical risk between patients receiving metformin, levothyroxine, or no other non-oncology drugs. Notably, there was no association between the consumption of levothyroxine and metformin and proliferation marker (Ki67) levels, but both drugs were significantly associated with progesterone-related features, suggesting that they influence genomic risk through estrogen-dependent signaling.Conclusions The results of this study indicate a significant impact of metformin and levothyroxine on clinical decisions in luminal BC, with potential impact on the clinical course of these patients.

【 授权许可】

CC BY|CC BY-NC-ND