Management of Vasomotor Symptoms in Women With Breast Cancer: From Pathophysiology to the Emerging Role of Neurokinin Receptor Antagonism

Vasomotor symptoms (VMS), encompassing hot flashes and night sweats, are among the most frequent and disruptive consequences of estrogen withdrawal in women with breast cancer.In this population, menopause may occur naturally or in association with cancer treatment, while the use of menopausal hormone therapy (MHT) is limited by concerns regarding oncological safety.The present narrative review synthesizes current understanding of the neuroendocrine pathophysiology of vasomotor symptoms, centered on the hypertrophy and hyperactivity of hypothalamic neurons co-expressing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy) following estrogen deprivation, and critically appraises the available non-hormonal management options, including selective serotonin reuptake inhibitors, serotoninnorepinephrine reuptake inhibitors, gabapentin, oxybutynin, and cognitive behavioral therapy (CBT).Particular emphasis is placed on the neurokinin receptor antagonists, a mechanistically targeted drug class that acts on the thermoregulatory pathways involved in VMS.Fezolinetant is a selective neurokinin-3 receptor antagonist evaluated in the SKYLIGHT program, while elinzanetant is a dual neurokinin-1 and neurokinin-3 receptor antagonist evaluated in the OASIS program, including a pivotal placebo-controlled trial in women experiencing vasomotor symptoms associated with endocrine therapy for breast cancer.Dedicated studies of fezolinetant in women with breast cancer are ongoing.Neurokinin receptor antagonism represents a promising non-hormonal therapeutic strategy for VMS in this population, although agentspecific safety considerations and the need for longer-term oncological safety data require further evaluation.