Letrozole, Anastrozole or Tamoxifen? Hormone Therapy for HR-Positive Breast Cancer Explained

If you have hormone receptor-positive (HR-positive) breast cancer, you will probably be offered a hormone tablet for several years. The most common are letrozole (Femara), anastrozole (Arimidex), exemestane (Aromasin) and tamoxifen. They all aim to stop oestrogen from feeding the cancer, but they do it in two different ways and suit different people. This guide explains the differences and what to expect.

What “hormone receptor-positive” means

Some breast cancers have receptors for the hormone oestrogen (and sometimes progesterone). Oestrogen attaches to these receptors and helps the cancer grow. Hormone therapy works by lowering oestrogen or stopping it from reaching the cancer cells¹. This is different from the hormone therapy used for menopause symptoms¹.

Two ways to block oestrogen

• Aromatase inhibitors (letrozole, anastrozole, exemestane) lower oestrogen. After the menopause, the ovaries stop making oestrogen, but the body still makes small amounts using an enzyme called aromatase. These medicines block that enzyme³⁵.
• Tamoxifen blocks oestrogen’s effect. It attaches to the oestrogen receptors in breast cells and blocks them. In some other parts of the body, such as bone, it acts more like oestrogen¹.

Who takes which

Before the menopause, the ovaries make too much aromatase for these tablets to block on their own. That is why women who have not been through the menopause only take an aromatase inhibitor alongside an injection or other treatment that switches off the ovaries¹. Some women take tamoxifen for 2 or 3 years and then switch to an aromatase inhibitor¹⁷.

Letrozole vs anastrozole vs exemestane

The three aromatase inhibitors do the same job and have similar side effects⁵. The practical differences are small:

Medicines affect people differently. If side effects from one aromatase inhibitor are a problem, your doctor may suggest switching to another³⁵.

How long you take it

After surgery for early breast cancer, letrozole is usually taken for about 5 years, and sometimes up to 10 years⁴. Hormone therapy taken for 5 years or more has been shown to lower the risk of breast cancer coming back and of dying from it¹. Your specialist can explain the likely benefit in your own situation, because it depends on things like your age and the features of your cancer³.

For advanced breast cancer, these tablets are often combined with a targeted medicine. See our guide to Ibrance, Kisqali and Verzenio.

Letrozole side effects

Because they lower oestrogen, aromatase inhibitors cause symptoms like the menopause. The common side effects of letrozole include²⁶:

• hot flushes and sweating
• joint pain and muscle or bone aches
• tiredness, dizziness and sleep problems
• low mood
• headache
• swelling of the hands or feet
• raised cholesterol
• mild hair thinning

Menopause-type symptoms often improve during the first months². Anastrozole and exemestane cause a similar pattern⁵.

Get medical help quickly for signs of a blood clot (throbbing or cramping pain, swelling, warmth and redness in a leg or arm), yellow skin or eyes, blurred vision, or signs of infection. Call emergency services for sudden chest pain or signs of a stroke, such as sudden weakness, a drooping face or difficulty speaking².

Tamoxifen side effects

Hot flushes are the most common side effect of tamoxifen⁸. It also has two less common but important risks⁸:

• Blood clots in the legs or lungs. Tell your doctor if you have had a clot before.
• Changes in the womb lining, including womb cancer. Report any unusual vaginal bleeding, changes in discharge, or pelvic pain or pressure promptly, and have regular gynaecology check-ups.

Protecting your bones

Oestrogen helps keep bones strong, so aromatase inhibitors can thin the bones over time and raise the risk of osteoporosis and fractures³⁶. To protect them:

• You may have a bone density scan before you start, after 1 or 2 years, and when you finish³.
• Your vitamin D level should be checked before you start an aromatase inhibitor⁷. See our guide to vitamin D testing and dosing.
• Your doctor may recommend a bone-strengthening medicine (a bisphosphonate), plus advice on exercise and diet³.

Interactions: tamoxifen and some antidepressants

Some antidepressants can make tamoxifen less effective. This matters because antidepressants are often used for low mood and for hot flushes. If you take one, ask your doctor whether it affects tamoxifen. Sertraline, citalopram and venlafaxine are among those doctors may suggest instead¹. Quinidine (a heart rhythm medicine), diphenhydramine (an antihistamine) and cimetidine (a stomach acid medicine) may also interfere with tamoxifen¹. Always tell your team about every medicine you take.

Staying on treatment when side effects are hard

Many people find side effects hardest in the first months. Some things that help:

• Hot flushes: cut down on spicy food, caffeine, smoking and alcohol, keep the room cool and use a fan².
• Aches: a pharmacist can suggest a suitable painkiller. See a doctor urgently for a sudden attack of pain in a joint².
• Tiredness: gentle exercise and regular sleep times can help².
• Switching: changing to a different hormone tablet, or a short break agreed with your specialist, can help when side effects are too much¹³.

Do not stop your tablets without talking to your doctor first³. If you forget a dose of letrozole, take it when you remember unless your next dose is due in less than 3 hours; never take two doses together⁴.

Pregnancy and contraception

Aromatase inhibitors and tamoxifen can harm an unborn baby⁶⁸. Some women find their periods return while taking letrozole; if this happens, use reliable contraception and tell your doctor³. Women taking tamoxifen should avoid pregnancy during treatment and for 2 months after stopping, using a barrier or non-hormonal method⁸.

Generic versions

We stock letrozole, including Fempro 2.5 mg and Letrafem 2.5 mg, anastrozole, including Femistra 1 mg, and exemestane, including Aromasin 25 mg. See all options on our letrozole, anastrozole and exemestane pages, or browse our breast cancer medicines. All need a prescription. We do not currently supply tamoxifen.

Frequently asked questions

Is letrozole better than tamoxifen?

Neither is better for everyone. Aromatase inhibitors like letrozole are mainly for women after the menopause, while tamoxifen can be used before and after the menopause and in men. The choice also depends on your bone health, your risk of blood clots and your other medicines.

Does letrozole cause weight gain?

Letrozole can change your appetite. Some people lose their appetite, while others feel hungrier. If you are putting on more weight than you want, ask your doctor or nurse about seeing a dietitian.

How long do you take letrozole?

Usually about 5 years after surgery for early breast cancer, and sometimes up to 10 years. Your specialist will decide the length with you.

Is letrozole chemotherapy?

No. Letrozole is a hormone therapy. It lowers oestrogen rather than killing dividing cells like chemotherapy. See our guide is it chemotherapy?

Can I drink alcohol with letrozole?

There is no evidence that alcohol causes problems with letrozole, but it can trigger hot flushes or redness in some people.

Sources & references

1. National Cancer Institute. Hormone Therapy for Breast Cancer. Updated 23 September 2026.
2. NHS. Side effects of letrozole. Page last reviewed 24 November 2023.
3. NHS. Common questions about letrozole. Page last reviewed 24 November 2023.
4. NHS. How and when to take letrozole. Page last reviewed 24 November 2023.
5. NHS. Common questions about anastrozole. Page last reviewed 6 March 2024.
6. US National Library of Medicine, DailyMed. Femara (letrozole) prescribing information.
7. US National Library of Medicine, DailyMed. Aromasin (exemestane) prescribing information.
8. US National Library of Medicine, DailyMed. Tamoxifen citrate tablets prescribing information.
9. NHS. How and when to take anastrozole. Page last reviewed 6 March 2024.

Related reading

• Letrozole vs clomiphene for fertility
• Ibrance vs Kisqali vs Verzenio
• Vitamin D testing and dosing
• When a cancer medicine stops working

This content is for informational purposes only and is not medical advice. Do not stop or change your hormone therapy without talking to your cancer team. Used as prescribed by a licensed medical professional.