Causal analyses of the impact of comorbid conditions and concomitant medications on response to neoadjuvant chemotherapy in breast cancer: analysis of a multicenter prospective cohort study (CANTO)

A-S Hamy; B Grandal; F Jochum; É Dumas; N Sella; A Kassara; S Barraud; T Dubois; A Ballesta; S Everhard; J Lemonnier; M Sauzey; A Bertaut; J-Y Blay; P Cottu; O Tredan; F Joly; P Gougis; B Asselain; A Latouche; I Vaz Luis; F Andre; F Reyal

doi:10.1016/j.esmoop.2025.104507

Causal analyses of the impact of comorbid conditions and concomitant medications on response to neoadjuvant chemotherapy in breast cancer: analysis of a multicenter prospective cohort study (CANTO)

ESMO Open. 2025 May;10(5):104507. doi: 10.1016/j.esmoop.2025.104507. Epub 2025 May 15.

Authors

A-S Hamy¹, B Grandal², F Jochum³, É Dumas⁴, N Sella⁵, A Kassara⁵, S Barraud¹, T Dubois⁶, A Ballesta⁷, S Everhard⁸, J Lemonnier⁸, M Sauzey⁹, A Bertaut¹⁰, J-Y Blay¹¹, P Cottu¹², O Tredan¹¹, F Joly¹³, P Gougis¹⁴, B Asselain¹⁵, A Latouche¹⁶, I Vaz Luis¹⁷, F Andre¹⁸, F Reyal¹⁹

Affiliations

¹ Department of Medical Oncology, Institut Curie, Université Paris Cité, Paris, France; Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France.
² Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France; Department of Breast, Gynecological and Reconstructive Surgery, Institut Curie, Université Paris Cité, Paris, France. Electronic address: beatriz.grandalrejo@curie.fr.
³ Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France; Department of Gynecology, Strasbourg University Hospital, Strasbourg, France.
⁴ Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France; MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France; INSERM, U900, Paris, France.
⁵ Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France.
⁶ Translational Research Department, Breast Cancer Biology Group, Institut Curie, PSL Research University, Paris, France.
⁷ INSERM UMR-S 900, Institut Curie, MINES ParisTech CBIO, PSL Research University, Saint-Cloud, France.
⁸ UNICANCER, Paris, France.
⁹ Department of Breast, Gynecological and Reconstructive Surgery, Institut Curie, Université Paris Cité, Paris, France.
¹⁰ Methodology and Biostatistics Unit, Centre Georges François Leclerc, Dijon, France.
¹¹ Department of Medical Oncology, Centre Léon Berard, Lyon, France.
¹² Department of Medical Oncology, Institut Curie, Université Paris Cité, Paris, France.
¹³ Department of Medical Oncology, Centre François Baclesse, Caen, France.
¹⁴ Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France; Department of Medical Oncology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique-Hôpitaux de Paris (AP-HP), Clinical Investigation Center (CIC-1901), Department of Pharmacology, Pitié-Salpêtrière Hospital, Paris, France.
¹⁵ Department of Biostatistics, Unicancer, Paris, France.
¹⁶ INSERM, U900, Paris, France; INSERM UMR-S 900, Institut Curie, MINES ParisTech CBIO, PSL Research University, Saint-Cloud, France; Conservatoire National des Arts et Métiers, Paris, France.
¹⁷ INSERM U981, Gustave Roussy, Villejuif, France; Interdisciplinary Department for the Organization of Patient Pathways (DIOPP), Gustave Roussy, Villejuif, France.
¹⁸ INSERM U981, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France.
¹⁹ Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris, Paris, France; Department of Breast, Gynecological and Reconstructive Surgery, Institut Curie, Université Paris Cité, Paris, France.

Abstract

Background: The incidence of breast cancer (BC) increases with age, together with the frequency of comorbid conditions and chronic concomitant medications. However, little evidence is available regarding their impact on response to treatment in the neoadjuvant setting.

Materials and methods: The aim of the study was to describe the comorbid conditions and concomitant medications in a population of BC patients and to assess whether the use of concomitant medications modifies the pathological complete response (pCR) rates to neoadjuvant chemotherapy (NAC) in a causal manner. Patients with invasive stage I-III BC from the French multicenter longitudinal prospective cohort CANcer TOxicities (CANTO) (NCT01993498) were included. Chronic concomitant medication intakes during NAC were binary-categorized at level 2 of the Anatomical Therapeutic Chemical (ATC) classification system. The average causal effect of concomitant medication on pCR was estimated using a doubly robust estimator (targeted maximum likelihood estimation) after adjustment on clinical and pathological factors, including notably chronic comorbid conditions.

Results: Out of 1420 patients with BC treated by NAC included in the study, 662 patients (46.6%) had at least one chronic comorbid condition and 355 patients (25.0%) declared at least one chronic concomitant medication. After causal analyses, several drug classes were significantly associated with pCR: drugs used in diabetes and lipid-modifying agents were significantly associated with increased response to NAC [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.03-3.27, P < 0.001 and OR 1.58, 95% CI 1.16-2.13, P < 0.001, respectively], while the use of cardiac therapy and diuretics was significantly associated with decreased response to NAC (OR 0.55, 95% CI 0.35-0.84, P < 0.001 and OR 0.43, 95% CI 0.21-0.85, P < 0.001, respectively).

Conclusions: The use of several classes of concomitant medication during NAC can be associated with changes in pCR rates. Further research is needed on the interactions between NAC and chronic non-anticancer drug use.

Keywords: breast cancer; comorbid conditions; concomitant medications; neoadjuvant chemotherapy.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Breast Neoplasms* / drug therapy
Breast Neoplasms* / epidemiology
Breast Neoplasms* / pathology
Comorbidity
Female
Humans
Middle Aged
Neoadjuvant Therapy* / methods
Prospective Studies