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Context: There is a growing interest in drug repurposing and pathological complete response (pCR) that may influence the progression and treatment of breast cancer (BC). However, few studies focus on the influence of comedications, i.e., non-anticancerous drugs taken for coexisting conditions in cancer patients on neoadjuvant chemotherapy (NAC), and even less regarding the impact of response to treatment and relapse in breast cancer. Objectives: To assess whether the use of comedications modifies pCR and patient relapse probability in BC. Methods: We retrospectively analyzed data from Saint-Louis Hospital (Paris, France). Characteristics from 664 patients with neoadjuvant chemotherapy. Response to chemotherapy was assessed by pathological complete response (pCR). We analyzed comedication according to levels 1 and 2 of the Anatomical Therapeutic Chemical Classification System (ATC). A chronic comedication was defined by a comedication declared at diagnosis, excluding local and/or non-continuous administration. To estimate the average causal effect of comedication on pCR, we employed Inverse Probability Weighting (IPW) and Super Learner strategy to pick the best regression model. We used a Cox multivariate regression model to analyze the average causal effect of comedications on relapse probability. Results: 664 patients were included in this study. The median age at inclusion was 51.4 years. Of 664 patients, 194 patients (29.2%) had at least one comedication (433 total comedications). The repartition of comedications, according to the 1st level of ATC, was as follows: Cardiovascular system (C): 40.2% (n=174), Nervous system (N): 23.8% (n=103) and Alimentary tract and metabolism (A): 15.2% (n=66). Among the population with collected pCR, 112 tumors achieved pCR (18.6%). After IPW adjusted for clinical, pathological, and treatment variables, C03 (Diuretics) was associated with an increased likelihood of positive pCR (C03 versus no C03, OR = 5.0, CI95% [1.25-12.2]). By contrast, N06 (Psychoanaleptics) was associated with a decrease in pCR rates (OR= 0.3, CI95% [0.1-0.6]). The multivariate survival analysis showed a significant effect on the relapse probability of Selective Serotonin reuptake inhibitors (SSRIs, NO6) (OR = 2.3 CI95% [1.2-4.4], p = 0.01). Discussion: In this observational analysis, the use of chronic cardiovascular diuretics (C03) during NAC was associated with improvement of pCR rates. On the contrary, Psychoanaleptics (N06) were significantly associated with lower pCR rates and a higher probability of relapse. This finding prompts for further research on the interactions between chemotherapy, nervous system drugs such as SSRIs, and pathological complete response. Citation Format: Anne-Sophie Hamy, Amyn Kassara, Hamid Hocini, Clementine Garin, Luis Teixeira, Caroline Cuvier, Paul Gougis, Elise Dumas, Fabien Reyal, Beatriz Grandal, Nadir Sella, Eric Daoud, Aurélien Latouche, Thierry Dubois, Annabelle Ballesta, Samar Alsafadi, Elaine Del Nery, Élodie Anthony, Benjamin Marande, Cedric de Bazelaire, Anne de Roquancourt, Catherine Michel, Sylvie Giacchetti, Marc Espie. Impact of comedications on pCR rates and relapse in breast cancer. Analysis of the Saint-Louis observational cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3348. |
