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

B. Waissengrin, T. Zahavi, M. Salmon-Divon, A. Goldberg, I. Wolf, T. Rubinek, T. Winkler, O. Farkash, A. Grinshpun, A. Zubkov, M. Khatib, S. S. Shachar, N. Keren, I. Carmi-Levy, U. Ben-David, A. Sonnenblick

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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.

Original languageEnglish
Article number100648
Pages (from-to)100648
Number of pages1
JournalESMO Open
Issue number6
Early online date30 Nov 2022
StatePublished - 1 Dec 2022


  • breast cancer
  • clinical risk
  • estrogen receptor
  • genomic risk
  • levothyroxine
  • metformin
  • Oncotype DX


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