Elacestrant and oral SERDs for ESR1-mutant disease

SERDs, selective oestrogen receptor degraders, are hormone treatments that attach to the oestrogen receptor on breast cancer cells and break it down, so the cancer can no longer use oestrogen to grow. Fulvestrant, the first SERD, is given as injections. Oral SERDs such as elacestrant are tablets. They are particularly useful for hormone receptor positive, HER2-negative metastatic breast cancer that has grown on earlier hormone therapy including a CDK4/6 inhibitor, and that carries a mutation in the ESR1 gene. In people with an ESR1 mutation, elacestrant controlled the cancer for longer than standard hormone therapy.

Why ESR1 mutations matter

After time on aromatase inhibitors, some cancers develop ESR1 mutations that keep the oestrogen receptor switched on even without oestrogen. These cancers stop responding to aromatase inhibitors but can still respond to drugs that break down the receptor.

How ESR1 is tested

ESR1 mutations are usually found with a blood test that detects tumour DNA, called a liquid biopsy, because they often appear only after earlier treatment.

Who may not benefit as much

People without an ESR1 mutation gain less from current oral SERDs, and those whose cancer is growing rapidly or affecting organs significantly may need chemotherapy or other treatment instead.

Oral SERDs add a convenient, generally well-tolerated option for hormone-sensitive metastatic breast cancer, especially when an ESR1 mutation is present. The benefit on its own is moderate, and cancers eventually become resistant.

The benefit depends on ESR1 status

Studies showed the clearest benefit in people with an ESR1 mutation. Without one, the advantage over standard hormone therapy is small.

A rapidly changing field

Several oral SERDs and combinations with other targeted drugs are being studied. Your oncologist can tell you which options and trials are currently relevant.

Access and cost

Availability of newer oral SERDs in India may be limited and costly. Ask about access, support programmes and trials.

What this page cannot tell you

It cannot tell you whether you have an ESR1 mutation or which treatment suits you. Ask your oncologist about testing.

Taking hormone treatment as a tablet at home suits many people, but a few habits help it work well.

Take tablets with food

Taking the tablet with a meal at the same time each day reduces feeling sick.

Check new medicines

Some medicines and grapefruit can affect levels of oral SERDs. Ask before starting anything new.

Keep a note of side effects

Writing down when sickness, tiredness or aches happen helps your team decide whether timing, food or other medicines could make treatment easier to live with.

Keep up scans and tests

Regular scans show whether treatment is working, and blood tests check cholesterol and liver function.

Oral SERDs are one of several options once hormone-sensitive metastatic breast cancer grows on a CDK4/6 inhibitor and hormone therapy.

Matching treatment to test results

An ESR1 mutation points towards an oral SERD. A PIK3CA mutation may point towards alpelisib, and a BRCA mutation towards a PARP inhibitor. Some cancers carry more than one mutation, and your oncologist decides the order.

When other treatments come first

If the cancer is growing quickly, causing significant symptoms or affecting the liver or lungs heavily, chemotherapy or an antibody-drug conjugate may be preferred because they tend to act faster.

Thinking about daily life

A daily tablet at home suits many people who find monthly injection visits hard, particularly those travelling long distances. Your preferences about hospital visits, side effects and cost are a legitimate part of the decision, so share them openly with your oncologist.

Clinical trials

Many trials are testing oral SERDs alone or in combination. Ask whether one might be suitable for you.