How does letrozole work, and who is it for? Postmenopausal hormone-receptor-positive breast cancer

Many breast cancers grow in response to oestrogen. These are called hormone receptor positive cancers, because the cancer cells carry receptors that oestrogen attaches to, switching on growth signals. Before menopause, most oestrogen comes from the ovaries. After menopause, the ovaries stop making it, but the body keeps producing smaller amounts in fat, muscle, skin and even breast tissue. This happens through an enzyme called aromatase, which converts other hormones, called androgens, into oestrogen. Letrozole is an aromatase inhibitor. It attaches to the aromatase enzyme and blocks it, so much less oestrogen is made throughout the body. With oestrogen levels very low, hormone receptor positive cancer cells lose a key growth signal, which can stop them growing, slow them down, or lower the chance that stray cells left after surgery will develop into a recurrence. Letrozole is described as a non-steroidal, reversible aromatase inhibitor, similar to anastrozole, while exemestane is a steroidal type that binds permanently. Because letrozole blocks oestrogen made outside the ovaries, it works best in women who have been through menopause. In women whose ovaries still work, lowering oestrogen can prompt the brain to signal the ovaries to make more, so letrozole is only used before menopause together with ovarian suppression. It has no benefit for cancers without hormone receptors.

It blocks an enzyme, not the receptor

Letrozole stops oestrogen being made, while tamoxifen blocks oestrogen at the receptor.

It suits postmenopausal women

It targets oestrogen made outside the ovaries, the main source after menopause.

The cancer must be hormone-sensitive

It only helps cancers with oestrogen or progesterone receptors.

Understanding the mechanism helps, but it also shows the limits of the medicine.

Some cancers become resistant

Over time, some hormone-sensitive cancers find other ways to grow despite low oestrogen.

Menopause is not always clear

After chemotherapy, periods may stop but ovaries can restart, so blood tests may be needed before letrozole.

Low oestrogen affects the whole body

The same mechanism that treats cancer causes side effects in bones, joints and the vagina.

Receptor strength matters

Cancers with strong hormone receptors usually respond better than those with weak receptors.

What this page cannot tell you

It cannot say how your cancer will respond. Your pathology report and oncologist can guide expectations.

Your team makes sure letrozole is right for you and that your health is protected during treatment.

Confirming hormone receptor status

The pathology report shows whether the cancer is oestrogen or progesterone receptor positive.

Confirming menopause

Your age, period history and sometimes hormone blood tests help confirm you are postmenopausal.

Baseline bone density

A bone density scan shows your starting bone health so changes can be tracked.

Other health checks

Cholesterol, liver function and a review of other medicines are often included.