Key points
- Letrozole (Femara) is a tablet that lowers the making of female hormone (oestrogen) in women after menopause and is used for hormone receptor-positive breast cancer [1].
- In a large study, letrozole prevented the cancer from coming back better than tamoxifen, especially in distant parts of the body [2].
- After 5 years of tamoxifen, continuing with letrozole made the cancer come back even less often [3].
- One 2.5 mg tablet a day, with or without food [1]. Take it every day until the end of the course (why?).
- The main side effects: hot flushes, joint pain, higher blood fats and weaker bones; bone health should be checked [1].
What is this drug and how does it work?
For physicians
Letrozole (brand name Femara) is a non-steroidal aromatase inhibitor first approved in the United States in 1997 [1].
The growth of many breast cancers depends on oestrogen. After menopause, the ovaries are no longer the main source of oestrogen, and most of the body's oestrogen comes from conversion of adrenal androgens to oestrogen by the enzyme aromatase in peripheral tissues and in the cancer tissue itself. By selectively inhibiting this enzyme, letrozole lowers blood oestrogen by 75 to 95% in postmenopausal women without disturbing cortisol or aldosterone synthesis [1].
This is why the label covers only postmenopausal women; in premenopausal women with active ovaries, an aromatase inhibitor is used only with concurrent ovarian suppression (as in the NATALEE trial) [4].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Early hormone receptor-positive breast cancer [1, 2]
- Early breast cancer [1, 3]
- Advanced or spread breast cancer that is hormone receptor-positive or of unknown receptor status [1, 5]
- Advanced breast cancer [1]
- High-risk early hormone receptor-positive, HER2-negative breast cancer [4]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Setting | Key evidence |
|---|---|---|
| Early hormone receptor-positive breast cancer | Adjuvant treatment after surgery [1] | BIG 1-98 trial in 8010 women: lower risk of a disease-free survival event compared with tamoxifen (HR 0.81; 95% CI 0.70 to 0.93), especially distant recurrence (HR 0.73) [2]. |
| Early breast cancer | Extended adjuvant treatment after 5 years of tamoxifen [1] | MA.17 trial in 5187 women: 4-year disease-free survival 93% with letrozole vs 87% with placebo [3]. |
| Advanced or metastatic breast cancer, hormone receptor-positive or unknown | First-line treatment [1] | In a phase 3 trial of 907 patients, time to progression was longer with letrozole than with tamoxifen (median 41 vs 26 weeks; HR 0.70) [5]. |
| Advanced breast cancer | Treatment after progression on antioestrogens (such as tamoxifen) [1] | Approved in the FDA label on the basis of second-line trials [1]. |
| High-risk early HR-positive/HER2-negative breast cancer | Endocrine backbone with ribociclib in adjuvant treatment | NATALEE trial: adding ribociclib to a non-steroidal aromatase inhibitor (letrozole or anastrozole) raised 3-year invasive disease-free survival from 87.1% to 90.4% (HR 0.75) [4]. |
The FDA label for Femara is for postmenopausal women. In adjuvant treatment the optimal duration is not known, and the median treatment duration in trials was 5 years [1].
How it is taken and dosing
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Treatment regimens and doses: index4 regimens
- Letrozole is a tablet taken once a day; you can take it with or without food [1]. Taking it at the same time every day helps you remember.
- As adjuvant treatment after surgery, it usually continues for several years, and in advanced disease it is taken as long as it works [1]. Never stop the drug without talking to your doctor.
- If you have liver cirrhosis or severe liver failure, tell your doctor; your dose may change [1].
- Until you know how the drug affects you, take care when driving or using machines, because tiredness, dizziness and sleepiness have been reported [1].
- Before starting: confirm postmenopausal status (the label covers postmenopausal women only); a pregnancy test in women of reproductive potential (pregnancy is a contraindication). Consider bone mineral density and serum cholesterol measurement [1].
- Liver and kidney: cirrhosis or severe hepatic impairment: reduce by 50%, i.e. 2.5 mg every other day; mild to moderate hepatic impairment: no adjustment. Renal impairment with creatinine clearance 10 mL/min or more: no adjustment [1].
- Dose reduction for toxicity: the FDA label defines no dose reduction levels [1].
- Missed dose: the FDA label gives no specific instruction for a missed dose [1].
- Monitoring: bone mineral density and serum cholesterol [1].
For physicians
Standard dosing (FDA label; postmenopausal women)
Adjuvant treatment of early hormone receptor-positive breast cancer
Postmenopausal womenCycle length: Continuous
Postmenopausal women [1]
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Letrozole | 2.5 mg | Oral (regardless of meals) | Once daily |
Extended adjuvant treatment after 5 years of tamoxifen
Postmenopausal women with early breast cancerCycle length: Continuous
Postmenopausal women with early breast cancer [1]
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Letrozole | 2.5 mg | Oral (regardless of meals) | Once daily |
Advanced or metastatic breast cancer, first line
Hormone receptor-positive or unknown; postmenopausal womenCycle length: Continuous
Hormone receptor-positive or unknown; postmenopausal women [1]
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Letrozole | 2.5 mg | Oral (regardless of meals) | Once daily |
Advanced breast cancer after progression on an antioestrogen
Postmenopausal womenCycle length: Continuous
Postmenopausal women [1]
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Letrozole | 2.5 mg | Oral (regardless of meals) | Once daily |
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Side effects
Common side effects
The most common side effects:
For physicians
| Adverse reaction | Letrozole | Tamoxifen |
|---|---|---|
| Hypercholesterolaemia | 52.3% | 28.6% |
| Hot flushes | 33.5% | 38.0% |
| Arthralgia/arthritis | 25.4% | 20.6% |
| Bone fractures (any time after starting) | 14.7% | 11.4% |
| Night sweats | 14.5% | 17.4% |
| Weight gain | 12.9% | 15.4% |
| Nausea | 11.6% | 11.3% |
| Fatigue | 9.6% | 10.2% |
| Myalgia | 9.0% | 8.7% |
| Vaginal bleeding | 5.3% | 13.1% |
| Osteoporosis | 5.1% | 2.7% |
Source: FDA label for Femara [1]. Most adverse reactions (in about 75% of patients who had one) were grade 1 or 2 [1].
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- Fractures: severe bone pain after a minor knock or fall [1].
- Heart problems: chest pain or pressure; slightly more common than with tamoxifen [1].
- Tiredness, dizziness and sleepiness that may make driving difficult [1].
- Harm to an unborn baby: it must not be used in pregnancy [1].
- Rare: liver inflammation, swelling of the face or throat, severe skin reactions and tendon problems [1].
For physicians
Letrozole has no boxed warning, but the drug label lists these warnings and precautions [1]:
- Decreased bone mineral density: in a two-year study, lumbar spine density fell by a median of 4.1% with letrozole, while it rose by 0.3% with tamoxifen. In MA-17 (extended treatment), new fractures occurred in 13.3% vs 7.8% and new osteoporosis in 14.5% vs 7.8% with placebo [1].
- Raised cholesterol: in BIG 1-98, lipid-lowering drugs were needed by 29% of letrozole patients vs 20% of tamoxifen patients; cholesterol monitoring is recommended [1].
- Cardiovascular events: during treatment in BIG 1-98, myocardial infarction occurred in 1.0% with letrozole vs 0.5% with tamoxifen, but thromboembolic events (2.1% vs 3.6%) and endometrial hyperplasia or cancer (0.3% vs 2.9%) were less frequent [1]. In MA-17, cardiovascular events during treatment were 9.8% vs 7.0% with placebo [1].
- Fatigue, dizziness and somnolence, which can affect driving and using machines [1].
- Embryo-fetal toxicity: use in pregnancy is contraindicated; miscarriage and birth defects have been reported after marketing [1].
- After marketing, hepatitis, angioedema, toxic epidermal necrolysis, erythema multiforme, carpal tunnel syndrome and tendon disorders (including tendon rupture and trigger finger) have been reported [1].
When should I call my doctor?
Contact your doctor without delay or go to the emergency department if you have these symptoms (these reactions have been reported in the drug label) [1]:
- Chest pain or pressure or sudden shortness of breath
- Sudden pain, swelling or warmth in one lower leg
- Swelling of the face, lips, tongue or throat, or difficulty swallowing or breathing
- A blistering or widespread rash, or mouth sores
- Yellowing of the skin or whites of the eyes
- Severe bone pain after a minor knock or fall (possible fracture)
- A possible pregnancy during treatment
Interactions, pregnancy and precautions
- Bone health: because letrozole lowers bone density, the drug label recommends monitoring bone mineral density (BMD) [1]. In postmenopausal women with early breast cancer, bone-strengthening drugs (bisphosphonates) reduced cancer recurrence in bone, deaths from breast cancer and fractures [6]. Talk to your doctor about whether you need a bone density scan and bone-protective medicines.
- Tamoxifen: taking it at the same time as tamoxifen lowers letrozole levels in the blood [1]. Starting letrozole straight after finishing tamoxifen does not reduce its effect [1].
- In drug interaction studies, cimetidine and warfarin had no clinically important interaction with letrozole [1].
- Pregnancy and contraception: in women who could become pregnant, a pregnancy test should be done before starting, and effective contraception used during treatment and for at least 3 weeks after the last dose [1].
- Breastfeeding: do not breastfeed during treatment and for at least 3 weeks after the last dose [1].
- Fertility: based on animal studies, letrozole may reduce fertility in women and men [1].
Frequently asked questions
Is letrozole suitable for women who have not yet gone through menopause?
How common is joint pain with letrozole?
For how many years do I need to take letrozole?
The best length of adjuvant treatment is not known; in the main studies, patients usually took the drug for about 5 years [1]. In some patients, continuing with letrozole after 5 years of tamoxifen is recommended, which in a large study made the cancer come back less often [3]. Your doctor sets the length of your treatment based on your risk of recurrence and side effects.
Is letrozole better than tamoxifen?
In postmenopausal women with early hormone receptor-positive breast cancer, a review of all the studies showed that this group of drugs (such as letrozole) lowers the chance of the cancer coming back by about a third compared with tamoxifen, with slightly fewer deaths from breast cancer at 10 years; on the other hand, bone fractures are more common and womb cancer less common [7].
Scientific evidence
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Key studies
4 itemsBreast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer
Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes
Ribociclib plus Endocrine Therapy in Early Breast Cancer
Related cancer types
References
7 referencesShow all references, 6 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3
- 4
- 5Superior Efficacy of Letrozole Versus Tamoxifen as First-Line Therapy for Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Study of the International Letrozole Breast Cancer Group
- 6Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials
- 7Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials
This page is based on reputable scientific sources and was last updated on 27 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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