Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer.

Abstract

Immunosurveillance plays an important role in breast cancer (BC) prognosis and progression, and can be geared by immunogenic chemotherapy. In a cohort of 1023 BC patients treated with neoadjuvant chemotherapy (NAC), 40% of the individuals took comedications mostly linked to aging and comorbidities. We systematically analyzed the off-target effects of 1178 concurrent comedications (classified according to the Anatomical Therapeutic Chemical (ATC) Classification System) on the density of tumor-infiltrating lymphocytes (TILs) and pathological complete responses (pCR). At level 1 of the ATC system, the main anatomical classes of drugs were those targeting the nervous system (class N, 39.1%), cardiovascular disorders (class C, 26.6%), alimentary and metabolism (class A, 16.9%), or hormonal preparations (class H, 6.5%). At level 2, the most frequent therapeutic classes were psycholeptics (N05), analgesics (N02), and psychoanaleptics (N06). Pre-NAC TIL density in triple-negative BC (TNBC) was influenced by medications from class H, N, and A, while TIL density in HER2+ BC was associated with the use of class C. Psycholeptics (N05) and agents acting on the renin-angiotensin system (C09) were independently associated with pCR in the whole population of BC or TNBC, and in HER2-positive BC, respectively. Importantly, level 3 hypnotics (N05C) alone were able to reduce tumor growth in BC bearing mice and increased the anti-cancer activity of cyclophosphamide in a T cell-dependent manner. These findings prompt for further exploration of drugs interactions in cancer, and for prospective drug-repositioning strategies to improve the efficacy of NAC in BC.

• Authors: Anne-Sophie Hamy, Lisa Derosa, Constance Valdelièvre, Satoru Yonekura, Paule Opolon, Maël Priour, Julien Guerin, Jean-Yves Pierga, Bernard Asselain, Diane De Croze, Alice Pinheiro, Marick Lae, Laure-Sophie Talagrand, Enora Laas, Lauren Darrigues, Beatriz Grandal, Elisabetta Marangoni, Elodie Montaudon, Guido Kroemer, Laurence Zitvogel, Fabien Reyal
• Journal: Oncoimmunology (Oncoimmunology) Vol. 9 Issue 1 Pg. 1677427 ( 2020) ISSN: 2162-4011 [Print] United States
• PMID: 32002287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Receptor, ErbB-2

Topics

• Animals
• Humans
• Lymphocytes, Tumor-Infiltrating
• Mice
• Neoadjuvant Therapy
• Prospective Studies
• Receptor, ErbB-2
• Triple Negative Breast Neoplasms (drug therapy)