Antibody-Drug Conjugates for Breast Cancer: How They Work and Who They Help

What are antibody-drug conjugates?

Antibody-drug conjugates, often shortened to ADCs, are a newer type of cancer treatment. Each one is made of two parts joined together: an antibody and a chemotherapy drug. The antibody is a type of protein that can recognise and stick to a particular target on the surface of cancer cells. The chemotherapy drug is the part that damages and kills those cells.

It can help to think of an ADC as a guided parcel. The antibody is the address label that finds the right house, and the chemotherapy is the parcel it delivers. Because the chemotherapy is aimed mainly at cells carrying the target, more of it can reach the cancer and, in theory, less of it spreads through the rest of the body. ADCs are sometimes called a 'targeted' or 'smart' chemotherapy for this reason.

Two ADCs that are used for breast cancer in the UK are trastuzumab deruxtecan, known by the brand name Enhertu, and sacituzumab govitecan, known by the brand name Trodelvy. According to Cancer Research UK, these are antibody-drug conjugates that combine a targeted antibody with a chemotherapy drug in a single treatment.

This page gives general information and is not personal medical advice. ADCs are specialist treatments and everyone's situation is different. Your oncologist, breast care nurse and GP know your own circumstances, so please always check with your treatment team about what is right for you.

How do they work?

Breast cancer cells can carry different proteins on their surface. Some of these proteins act like a flag that an antibody can lock onto. ADCs are designed so that their antibody matches a flag found on many breast cancer cells but on fewer healthy cells.

Trastuzumab deruxtecan (Enhertu) targets a protein called HER2. According to Cancer Research UK, it combines trastuzumab, an antibody that attaches to HER2 (the same target as the older drug Herceptin), with a chemotherapy drug called deruxtecan, sometimes written as DXd. When the antibody attaches to a HER2 cancer cell, it carries the chemotherapy inside, where it becomes active and damages the cell.

Sacituzumab govitecan (Trodelvy) targets a different protein, called Trop-2, which sits at high levels on the surface of many breast cancer cells. Cancer Research UK explains that the antibody part attaches to Trop-2 and delivers its chemotherapy component directly inside the cell, stopping the cell multiplying and eventually causing it to die.

Once the chemotherapy is released, it works by damaging the DNA inside the cancer cell. The cell can no longer divide and grow, and it dies. Because the chemotherapy is carried in by the antibody, it is concentrated more where it is needed, although some healthy cells are still affected, which is why ADCs still have side effects.

Who might they help?

ADCs are mainly used for breast cancer that has spread to other parts of the body (secondary, advanced or metastatic breast cancer) or that cannot be removed by surgery (unresectable). They are not usually a first treatment. They tend to be offered after one or more other treatments have already been tried. Which ADC, if any, might suit you depends on the type of breast cancer you have and on your earlier treatment.

Trastuzumab deruxtecan (Enhertu) is used for HER2-positive breast cancer, meaning cancer with high levels of the HER2 protein. According to Cancer Research UK, it is a treatment for HER2-positive breast cancer that has spread or is unresectable, usually after one or more earlier treatments that targeted HER2. It has also been studied in HER2-low breast cancer, where cells carry smaller amounts of HER2 than in HER2-positive cancer.

Sacituzumab govitecan (Trodelvy) is used for triple-negative breast cancer. This is a type that does not have HER2 or the hormone receptors that some other breast cancers have, which means certain common treatments do not work for it. NICE recommends sacituzumab govitecan as an option for adults with unresectable triple-negative breast cancer that has spread (advanced or metastatic) when it has already been treated with two or more other therapies, at least one of which was for advanced disease.

Your team will look at your biopsy and scan results to work out whether your cancer carries the right target, such as HER2, and whether an ADC is a suitable option for you. If you are not sure why a particular treatment has or has not been offered, it is always reasonable to ask your oncologist or breast care nurse to explain.

How they are given

ADCs are given as a drip into a vein (an infusion), not as tablets. Cancer Research UK explains that sacituzumab govitecan is given into the bloodstream, often through a central line, a PICC line, a portacath or a cannula in the arm. It is given on days 1 and 8 of a 21-day cycle, with the first infusion taking around 3 hours and later doses usually 1 to 2 hours. Trastuzumab deruxtecan is also given as an infusion into a vein, on a repeating cycle.

Treatment is given in cycles, usually with a rest period in between to let your body recover. You will normally have blood tests before each cycle to check that you are well enough to continue. Treatment usually carries on for as long as it is helping and the side effects can be managed. Your team will keep reviewing how you are doing with scans and check-ups.

Before and during treatment you may be given other medicines, such as anti-sickness drugs, to help prevent or ease side effects. Tell your nurse straight away if you feel unwell during an infusion, as some people can have an allergic-type reaction while the drip is running.

Side effects to be aware of

Like all cancer treatments, ADCs can cause side effects, and these vary from person to person. Many can be managed well with support from your team. Your nurse or doctor will give you information about what to look out for and a number to call if you feel unwell between appointments.

According to Cancer Research UK, common side effects of these ADCs can include:

• Feeling sick (nausea) or being sick (vomiting)
• Diarrhoea or constipation
• Tiredness and a general feeling of weakness (fatigue)
• A higher risk of infection, because of lower levels of white blood cells
• Anaemia (a low level of red blood cells), which can cause breathlessness and a pale appearance
• Hair loss or thinning
• Allergic-type reactions while the drip is being given

One side effect to be especially aware of with trastuzumab deruxtecan (Enhertu) is a lung problem called interstitial lung disease, or pneumonitis. This is inflammation of the lungs that can cause a new or worsening cough, breathlessness, or a fever. It is uncommon, but it can be serious, so it is important to report breathing symptoms to your team straight away rather than waiting. Your team may pause treatment and do lung scans to check for it.

Because ADCs can lower the number of blood cells your body makes, your team will watch your blood counts closely. Contact your treatment team urgently, day or night, if you feel feverish, shivery or generally very unwell, as this can be a sign of infection that needs quick treatment. Never wait to see if you feel better on your own.

This is not a full list of every possible side effect. The patient information leaflet that comes with your treatment, and your breast care nurse, are the best sources of detailed advice for your own situation.

Where ADCs stand on the NHS in the UK

Whether a treatment is available on the NHS depends on decisions by NICE (the National Institute for Health and Care Excellence) in England, Wales and Northern Ireland, and by the Scottish Medicines Consortium in Scotland. These bodies look at how well a treatment works and whether it is good value for money. This means access to ADCs can change over time and can differ between the nations of the UK.

NICE recommends sacituzumab govitecan (Trodelvy) as an option on the NHS for adults with unresectable triple-negative breast cancer that has spread, after two or more previous treatments (at least one of which was for advanced disease). Trastuzumab deruxtecan (Enhertu) is recommended by NICE for some people with HER2-positive breast cancer that has spread or is unresectable after two or more earlier anti-HER2 treatments, with access supported through the Cancer Drugs Fund.

Decisions about ADCs for HER2-low breast cancer have been more difficult. NICE has not recommended trastuzumab deruxtecan for HER2-low breast cancer on the NHS in England, mainly because of its cost, even though the evidence showed it could help people live longer. This decision has been the subject of strong concern from breast cancer charities. Access has differed across the UK, which campaigners describe as a 'postcode lottery'.

Because these decisions are reviewed and can change, the most up-to-date position is always on the NICE website, the Scottish Medicines Consortium website, or from your own treatment team. If a treatment is not routinely funded, your oncologist can explain other options, including clinical trials, which sometimes give access to newer treatments.

Why access and early detection matter

ADCs are an encouraging example of how breast cancer treatment is improving. But like many newer treatments, they are mainly used for advanced breast cancer and they are expensive, which is part of why access can be uneven. Finding breast cancer earlier, before it spreads, usually means more treatment options and a better chance of successful treatment.

Our charity's mission is to support earlier detection and fairer access for everyone, including people in underserved and lower-income communities who can face extra barriers to getting checked and treated. Knowing the warning signs of breast cancer, attending NHS screening when you are invited, and getting any changes checked by your GP all help to catch problems sooner. Newer treatments work best alongside, not instead of, finding cancer early.

If you have any worries about breast changes, your treatment, or whether a particular drug might be right for you, please speak to your GP or treatment team. They can give you advice based on your own health and circumstances.