Neurokinin 1/3 Receptor Antagonists for Vasomotor Symptoms in Women with Breast Cancer

Endocrine therapy remains a cornerstone treatment for patients with hormone receptor-positive breast cancer. However, its benefits are often undermined by treatment-related adverse events, including vasomotor symptoms (VMS) such as hot flashes and night sweats. These symptoms can substantially impair quality of life and contribute to poor treatment adherence, thereby reducing the effectiveness of endocrine therapy and potentially increasing the risk of disease recurrence. While hormone replacement therapy is effective for managing postmenopausal hot flashes in the general population, it is contraindicated in women receiving endocrine, essentially an anti-estrogen, breast cancer treatment. Therefore, safe and effective non-hormonal strategies are required. Traditional pharmaceutical options, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin and clonidine, provide modest benefit but are often limited by their own side effects or drug-drug interactions with endocrine therapies. More recently, targeted approaches using neurokinin receptor antagonists, including fezolinetant and elinzanetant, have shown promise in reducing the frequency and severity of VMS. This review highlights the rationale, evidence and clinical potential of neurokinin receptor antagonists as emerging non-hormonal options for managing breast cancer-related VMS. PEER REVIEWED ARTICLE **Peer reviewers:** PD Dr Mattea Reinisch, Interdisciplinary Breast Unit, University Hospital Mannheim, Mannheim, Germany. Dr Anton Oseledchyk, Department of Biomedicine and Division of Oncology, Basel University Hospital and University of Basel, Basel, Switzerland. Received on September 15, 2025; accepted after peer review on December 05, 2025; published online on December 08, 2025.