Who is this for?
This is for people troubled by frequent, moderate-to-severe hot flashes who cannot — or prefer not to — take hormone (estrogen) therapy. Two groups matter most here:
- People treated for hormone-receptor-positive breast cancer who take anti-estrogen (“endocrine”) therapy such as tamoxifen or an aromatase inhibitor. These drugs commonly cause hot flashes, and estrogen replacement is off the table because it could feed the cancer.
- Women going through menopause who cannot take hormones (for medical reasons) or choose not to.
What kind of evidence is this?
This is a review of two recent phase III trials of a new class of drug for hot flashes — the goal being to help people feel better during and after cancer treatment, rather than to treat the cancer itself.
Background: why this is a real problem — and the new idea
For women with hormone-receptor-positive breast cancer, years of anti-estrogen therapy dramatically lower the chance of the cancer returning. But the same drop in estrogen that starves the cancer also triggers hot flashes — often severe, and sometimes bad enough that people quietly stop taking their pills.
The usual fix for menopausal hot flashes — estrogen replacement — is unsafe here, because adding estrogen back could stimulate the cancer. The older non-hormonal options (certain antidepressants such as venlafaxine, or gabapentin and clonidine) help only modestly, come with their own side effects, and one of them, paroxetine, can actually interfere with tamoxifen. So there has long been an unmet need.
The new idea comes from understanding why hot flashes happen. Deep in the brain sits a cluster of nerve cells (“KNDy” neurons) that help run the body’s thermostat. When estrogen falls, these neurons become overactive and fire off a chemical messenger called neurokinin B, which trips a false “too hot” alarm — the hot flash. The new drugs, neurokinin (NK) receptor antagonists, simply block that messenger.
The two trials
Two large, placebo-controlled phase III trials tested drugs from this class. It is important to know that they studied different drugs in different groups of people, so their results should be read side by side, not as a head-to-head comparison:
- Elinzanetant (OASIS-4, NEJM 2025) — blocks two receptors (NK-1 and NK-3). This trial enrolled 474 women taking endocrine therapy for hormone-receptor-positive breast cancer (or to prevent it) — so it speaks directly to the breast cancer setting. Elinzanetant or placebo, once daily.
- Fezolinetant (DAYLIGHT, BMJ 2024) — blocks one receptor (NK-3), and is already approved for menopausal hot flashes. This trial enrolled 453 menopausal women who were unsuitable for hormone therapy for various reasons — a general group, not specifically breast cancer patients. Fezolinetant or placebo, once daily.
A note before the results
Many women with estrogen-sensitive breast cancer suffer from hot flashes. Not only does chemotherapy induce menopause, but for younger women an important treatment strategy is to induce an artificial menopause for years at a time — and one of the most common symptoms of menopause is hot flashes. More than just a nuisance, they interfere with sleep and well-being. This new class of drugs, the NK-antagonists, is game-changing for these women.
Results: what they found
Both drugs clearly reduced hot flashes compared with placebo. Because elinzanetant is the one tested directly in women on breast cancer therapy, its results are the most relevant here.
Elinzanetant vs placebo — in women on breast cancer endocrine therapy (OASIS-4)
Nearly 3 in 4 people on elinzanetant had at least a 50% reduction in hot flashes, roughly double the placebo group.
By 12 weeks, hot flashes dropped by about 8 a day with elinzanetant versus about 4 with placebo — a clear, meaningful difference. Benefit appeared within the first week.
Both improved significantly more with elinzanetant than placebo. Tellingly, 92% of those who finished the year chose to continue the drug into an optional 2-year extension.
Side effects were mostly mild (sleepiness, fatigue, headache); serious side effects were uncommon (2.5% vs 0.6%) and there was no signal of liver harm. Importantly, elinzanetant did not change the blood levels of tamoxifen or aromatase inhibitors — so it should not interfere with the breast cancer treatment itself.
The other drug: fezolinetant (DAYLIGHT)
Fezolinetant also significantly cut hot flashes versus placebo over 24 weeks, with better sleep and quality of life, and benefit again within the first week. It is already approved for menopausal hot flashes. But two caveats matter for cancer patients: this trial was in a general group of women unsuitable for hormones — not specifically breast cancer patients — so using it in that setting is currently off-label and less well studied. And fezolinetant requires periodic liver blood tests, because a small number of people develop elevated liver enzymes on it.
Why can’t people treated for breast cancer just take estrogen (HRT) for hot flashes?
Most breast cancers that cause hot-flash trouble are “hormone-receptor-positive,” meaning estrogen fuels their growth. The entire point of endocrine therapy (tamoxifen, aromatase inhibitors) is to remove or block estrogen so the cancer can’t use it. Giving estrogen back as hormone replacement would work against that — and studies have linked it to a higher risk of the cancer returning. That is exactly why a genuinely effective non-hormonal option is so valuable.
How is this different from older options like venlafaxine or gabapentin?
Antidepressants (such as venlafaxine or paroxetine), gabapentin, and clonidine have been used off-label for hot flashes for years. They help some people, but the benefit is usually modest and inconsistent, and each has its own side effects. One, paroxetine, can even blunt how well tamoxifen works, so it’s avoided in that setting. The NK-receptor antagonists are different because they target the actual brain mechanism behind hot flashes, and in these trials the effect was larger. They are, however, newer and more expensive, and long-term experience is still building.
The bottom line
Hot flashes from anti-estrogen breast cancer therapy are common, genuinely disruptive, and hard to treat because hormone replacement is unsafe. A new class of non-hormonal pills — the NK-receptor antagonists — targets the brain circuit that causes hot flashes. Elinzanetant, tested directly in women on breast cancer endocrine therapy, roughly halved hot flashes in about three-quarters of patients, improved sleep and quality of life, and did not interfere with the cancer drugs. Fezolinetant, an approved cousin, also works well but was studied in a general menopausal population rather than breast cancer specifically.
What this could mean for you
- Hot flashes are worth raising. They’re not just a nuisance — untreated, they can lead people to stop cancer medication that is protecting them. Tell your team if they’re bad.
- There is now a targeted, non-hormonal option. Elinzanetant was designed for exactly this situation and does not appear to interfere with tamoxifen or aromatase inhibitors.
- Availability may vary. These are new drugs; approval and coverage for the breast cancer setting differ by country. Fezolinetant is approved for menopause but its use in breast cancer patients is off-label and needs liver monitoring.
- These trials measured symptoms, not cancer outcomes. They did not test whether the drugs affect cancer recurrence or survival — reassuringly, elinzanetant didn’t alter the cancer-drug levels, but long-term cancer safety is still being followed.
Questions & comments
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