Muna Al-Khaifi, Lead of Breast Cancer Survivorship Program and GP Oncologist at the Mount Sinai Hospital (Toronto), Sinai Health, presents this article on vasomotor symptoms among cancer survivors. This piece reviews current evidence and emerging therapeutic approaches, highlighting the clinical and quality-of-life impact of hot flashes and night sweats, as well as their influence on treatment adherence and long-term outcomes in breast cancer survivors.
Vasomotor Symptoms Among Cancer Survivors: Current Evidence and Evolving Therapeutic Approaches
Optimizing the management of vasomotor symptoms associated with cancer treatment can improve not only quality of life, but also survival.
Vasomotor symptoms (VMS), including hot flashes and night sweats, are among the most common and distressing complications experienced by breast cancer survivors. While often perceived as secondary side effects of treatment, these symptoms carry substantial clinical significance. For many patients, VMS represent a persistent and disruptive burden that affects daily functioning, sleep, emotional well-being, and ultimately, the ability to adhere to life-prolonging therapies.
Burden and Clinical Impact
VMS are highly prevalent in patients undergoing endocrine therapy. Approximately 70-80% of women treated with tamoxifen experience hot flashes, with prevalence rising to over 90% in those receiving ovarian suppression. These symptoms are driven by estrogen deprivation, which disrupts hypothalamic thermoregulation through alterations in neurotransmitters such as norepinephrine and serotonin, leading to a narrowing of the thermoneutral zone. The burden of VMS extends far beyond physical discomfort. These symptoms are strongly associated with sleep disruption, fatigue, impaired cognitive function, anxiety, and depression. Together, they significantly impair quality of life and daily functioning.
Importantly, VMS also influence treatment adherence. Evidence suggests that up to 20-25% of patients discontinue endocrine therapy prematurely due to uncontrolled symptoms. This is particularly concerning in younger and higher-risk patients, where adherence is closely linked to improved long-term outcomes.
VMS should therefore be viewed not only as a quality-of-life issue, but as a factor that may influence cancer outcomes.
Current Management
Management of VMS in breast cancer survivors remains complex. While menopausal hormone therapy is the most effective treatment in the general population, it is generally contraindicated in hormone receptor–positive breast cancer. As a result, clinicians rely on non-hormonal strategies supported by survivorship guidelines such as those from the National Comprehensive Cancer Network.
Non-hormonal pharmacologic options provide meaningful symptom relief, though response and tolerability vary. Gabapentin is among the most well-studied agents, with consistent evidence demonstrating reductions in symptom frequency and severity, supported by randomized trials and recent systematic reviews. It may be particularly helpful for nocturnal symptoms and sleep, although sedation can limit its use. Pregabalin has also shown efficacy but is often limited by side effects.
SNRIs and SSRIs, particularly venlafaxine and desvenlafaxine, reduce hot flashes and may offer additional benefit for mood symptoms. Importantly, strong CYP2D6 inhibitors such as paroxetine and fluoxetine should generally be avoided in patients receiving tamoxifen. Clonidine provides modest benefit but is often limited by side effects. Oxybutynin has emerged as a promising option, with randomized trials demonstrating meaningful reductions in symptom frequency and improvements in quality of life.
Non-pharmacological approaches remain an important component of care. Cognitive behavioral therapy has the strongest evidence, particularly for improving sleep and symptom perception, although access remains a barrier. Other strategies, including acupuncture, weight loss, and lifestyle interventions, may provide modest benefit but are often insufficient as standalone therapies in patients with moderate to severe symptoms.
Emerging Therapies
Recent advances in the understanding of thermoregulation have led to the development of targeted therapies that represent a meaningful shift in VMS management. Neurokinin receptor antagonists, including fezolinetant and elinzanetant, directly target hypothalamic pathways involved in VMS.
Phase 3 trials, including the OASIS-4 study, have demonstrated rapid and significant reductions in symptom frequency and severity, with favorable tolerability profiles. These therapies represent a transition toward mechanism-based treatment and may significantly expand options for breast cancer survivors. While early safety data are reassuring, long-term outcomes continue to be evaluated.
Here are my thoughts:
- Emerging therapies are practice-changing.
Neurokinin receptor antagonists show strong efficacy and reassuring short-term safety. While long-term data are still evolving, they represent a meaningful shift in how we approach vasomotor symptoms and should be considered in appropriate patients where access allows.
- Management should be individualized and symptom-cluster driven.
In clinical practice, patients rarely present with isolated vasomotor symptoms. These symptoms often coexist with sleep disturbance, mood changes, fatigue, and other menopausal symptoms. Selecting therapies such as SNRIs or gabapentin can provide dual benefit, particularly for patients struggling with multiple overlapping symptoms. At the same time, drug interactions-especially with tamoxifen metabolism-must be carefully considered.
- Treating VMS is not just about comfort-it has broader clinical implications, including survival outcomes.
When symptoms are effectively managed, patients sleep better, function better, and feel better. More importantly, they are more likely to remain on treatment. This is particularly critical in younger and higher-risk patients, where early discontinuation of endocrine therapy may compromise long-term outcomes.
- Non-pharmacological strategies remain essential-but often insufficient alone.
These approaches should be part of every discussion. However, for patients with moderate to severe symptoms, they are rarely enough on their own. Cognitive behavioral therapy has the strongest evidence, but access and cost remain real barriers. Lifestyle interventions may help, but expectations should be realistic. That being said, lifestyle modifications, including physical activity, are supported by strong evidence for reducing fatigue, improving well-being, and addressing psychological symptoms.
- Patient-centered, ongoing care is critical.
It is important to realize that not all patients want additional medications, especially when already managing multiple side effects. These conversations should not happen once-they should be revisited over time. Symptoms evolve, preferences change, patients’ values and beliefs, and care needs to adapt accordingly. A longitudinal, patient-centred approach is essential.
Vasomotor symptoms remain a prevalent and impactful challenge for breast cancer survivors, significantly affecting quality of life and treatment adherence. Despite advances in management, they remain under-recognized and undertreated in clinical practice. As therapeutic options expand and our understanding of survivorship deepens, it is time to move beyond viewing VMS as a secondary concern. These symptoms influence not only how patients feel, but how they function, adhere to treatment, and ultimately, how they fare over time.
As cancer outcomes continue to improve, the definition of success in oncology must evolve beyond survival alone to include the quality of life patients experience with, through, and beyond cancer.
Key References and Evidence Base
- National Comprehensive Cancer Network (2025).
- American Society of Clinical Oncology. Survivorship and symptom management guidance.
- Oncology Nursing Society.
- Journal of Clinical Oncology (2025). Cardoso F et al. Phase 3 OASIS-4 Trial (elinzanetant).
- JNCI Cancer Spectrum (2020). Leon-Ferre RA et al. Oxybutynin randomized trial (ACCRU SC-1603).
- Proceedings (Baylor University Medical Center) (2025). Systematic review and meta-analysis of fezolinetant.
- 2026 systematic review of non-hormonal therapies for vasomotor symptoms (randomized controlled trial–based meta-analysis).
- The Oncologist (2025). Review on vasomotor symptoms and treatment adherence in breast cancer survivors.
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