Hamy A-S, Grandal B, Jochum F, Dumas É, Sella N, Kassara A, Barraud S, Dubois T, Ballesta A, Everhard S, Lemonnier J, Sauzey M, Bertaut A, Blay J-Y, Cottu P, Tredan O, Joly F, Gougis P, Asselain B, Latouche A, Vaz Luis I, Andre F, Reyal F
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.
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.
ESMO Open. 2025 May;10(5):104507. doi: 10.1016/j.esmoop.2025.104507. Epub 2025 May 15.
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.
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.
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).
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.
乳腺癌（BC）的发病率随年龄增长而上升，同时合并症和长期伴随用药的频率也随之增加。然而，关于它们对新辅助治疗反应的影响，目前几乎没有证据。
本研究的目的是描述BC患者群体中的合并症和伴随用药情况，并评估伴随用药的使用是否以因果关系改变了新辅助化疗（NAC）的病理完全缓解（pCR）率。纳入了来自法国多中心纵向前瞻性队列“癌症毒性”（CANTO）（NCT01993498）的I-III期浸润性BC患者。NAC期间长期伴随用药的摄入在解剖治疗化学（ATC）分类系统的第2级进行二元分类。在对临床和病理因素（尤其是慢性合并症）进行调整后，使用双重稳健估计器（靶向最大似然估计）估计伴随用药对pCR的平均因果效应。
在本研究纳入的1420例接受NAC治疗的BC患者中，662例患者（46.6%）至少有一种慢性合并症，355例患者（25.0%）声明至少有一种长期伴随用药。经过因果分析，几类药物与pCR显著相关：用于糖尿病的药物和调脂药与对NAC反应增加显著相关[比值比（OR）分别为1.86，95%置信区间（CI）为1.03 - 3.27，P < 0.001和OR 1.58，95%CI为1.16 - 2.13，P < 0.001]，而心脏治疗药物和利尿剂的使用与对NAC反应降低显著相关（OR分别为0.55，95%CI为0.35 - 0.84，P < 0.001和OR 0.43，95%CI为0.21 - 0.85，P < 0.001）。
NAC期间使用几类伴随用药可能与pCR率的变化有关。需要进一步研究NAC与长期非抗癌药物使用之间的相互作用。
