MINI REVIEW article
Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1654353
Polypharmacy Driven Synergistic Toxicities in Elderly Breast Cancer Chemotherapy Drug management and adverse drug reactions: A mini review
Provisionally accepted
- 1Department of Clinical Laboratory, Peking University First Hospital Taiyuan Branch, Taiyuan, China
- 2First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Breast cancer is increasingly diagnosed in older women (median age ≈ 63 years), and chemotherapy outcomes are clouded by a polypharmacy landscape-defined here as ≥5 concurrent medications-that magnifies toxicity beyond single-agent expectations. Prospective geriatric-oncology cohorts reveal a median of eleven concomitant drugs and clinically relevant potential drug-drug interactions (rPDDI) in up to 75 % of patients; each level-1 conflict almost doubles grade 3-4 non-haematological events, while polypharmacy-frailty indices outperform chronological age for predicting unplanned hospitalisation. Age-linked gastric alkalisation, cytochrome-P450 attrition and renal decline compress pharmacokinetic space: cimetidine lifts epirubicin exposure by 39 %, proton-pump inhibitors halve palbociclib troughs yet heighten neutropenia, and triazole antifungals quadruple free vincristine levels, yielding neuropathy in 87 % of recipients. Beyond kinetics, overlapping end-organ liabilities-anthracycline-trastuzumab cardiotoxicity, taxane-β-blocker arrhythmia, capecitabine-warfarin haemorrhage-translate polypharmacy into a synergistic toxicity premium that erodes functional independence. Pharmacist-led reconciliation coupled with algorithmic deprescribing removes ≥ 1 potentially inappropriate medication in 80 % of elders, while electronic rPDDI alerting and DPYD/CYP2D6 genotyping halve severe events without sacrificing efficacy. Composite scores integrating regimen complexity with genomic risk and circulating toxicity markers are emerging as real-time sentinels. By weaving mechanistic, epidemiologic and implementation evidence, this review charts how polypharmacy propels synergistic toxicities in elderly breast-cancer chemotherapy and delineates stewardship frameworks poised to reconcile oncologic potency with geriatric safety.
Keywords: Polypharmacy, Drugdrug interactions, Elderly breast cancer, Synergistic toxicity, adverse drug reactions
Received: 26 Jun 2025; Accepted: 05 Aug 2025.
Copyright: © 2025 Wang, Yang, Zhang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hong Yang, Department of Clinical Laboratory, Peking University First Hospital Taiyuan Branch, Taiyuan, China
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