Key unanswered questions in the management of VMS in patients with breast cancer include the long-term oncologic impact of NK receptor antagonists, the broader role of patient-reported outcomes in guiding therapy selection, and the need for prospective observational studies to evaluate real-world outcomes.
Effective management of VMS in patients with breast cancer requires individualized assessment and shared decision-making, with elinzanetant (Lynkuet) emerging as the preferred pharmacologic option for patients with moderate-to-severe symptoms given its early onset of action, NCCN-preferred status, and the most robust evidence base in this population.
An analysis from OASIS-4 demonstrated that elinzanetant (Lynkuet) consistently improved sleep disturbance and menopause-related quality of life across all endocrine therapy subgroups—with patients transitioning from moderate to normal sleep disturbance range by week 12—and that these benefits were sustained through 52 weeks.
In the phase 3 OASIS-4 trial (NCT05587296), elinzanetant (Lynkuet) produced clinically meaningful reductions in moderate-to-severe vasomotor symptoms frequency—beginning as early as week 1—compared with placebo, with improvements extending across all menopause-related quality-of-life domains.
Hyperactivation of hypothalamic KNDy neurons—which express kisspeptin, neurokinin B, and dynorphin—drives VMS during estrogen deprivation, providing the mechanistic basis for dual NK1/NK3 receptor antagonism as a nonhormonal strategy that may also improve sleep quality.
Vasomotor symptoms affect more than 50% of patients receiving endocrine therapy for hormone receptor–positive breast cancer and can reach 90% in younger patients on ovarian function suppression, with more than 20% of affected patients discontinuing treatment—a factor directly linked to increased recurrence risk and reduced survival.
