Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer. (1st January 2020)

• Record Type: Journal Article
• Authors: Hamy, Anne-Sophie; Derosa, Lisa; Valdelièvre, Constance; Yonekura, Satoru; Opolon, Paule; Priour, Maël; Guerin, Julien; Pierga, Jean-Yves; Asselain, Bernard; De Croze, Diane; Pinheiro, Alice; Lae, Marick; Talagrand, Laure-Sophie; Laas, Enora; Darrigues, Lauren; Grandal, Beatriz; Marangoni, Elisabetta; Montaudon, Elodie; Kroemer, Guido; Zitvogel, Laurence; Reyal, Fabien
• Is Part Of: Oncoimmunology. Volume 9:Number 1(2020)
• Publication Date: 2020-01-01
• Subjects: Breast cancer -- immunomodulation -- comedication -- pCR -- TILs; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1677427
• Languages: English
• ISSNs: 2162-402X

Abstract

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.