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

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

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.