THIS CHAPTER COVERS targeted therapies used to treat HER2-positive breast cancers. But what does ‘HER2-positive’ actually mean? Every breast cancer cell produces a protein called Human Epidermal Growth Factor Receptor 2, called ‘HER2’. HER2-positive cancers express very high levels of HER2, and 15–20 per cent of all breast cancers are HER2-positive (HER2+ve). The extra HER2 protein stimulates the cells to divide and grow much faster than HER2-negative (HER2-ve) cancers.
Years ago, HER2-positive cancers had a poor prognosis, but this was before the introduction of drugs like Herceptin. In 2012, a big review of research trials by the Cochrane Collaboration involving almost 12,000 women showed that Herceptin prevents one-third of breast cancer deaths in HER2-positive patients.
If your core biopsy (see here) shows an invasive cancer, it is first tested for HER2 positivity using a method called ‘immunohistochemistry’. This gives a score of 0, 1, 2 or 3. A score of 0 or 1 means that your cancer is HER2-negative. A score of 3 means that your cancer is HER2-positive. A score of 2 is a borderline result, and another test called ‘In Situ Hybridisation’ (FISH or CISH) is then done to confirm whether your cancer is HER2-positive or negative. Liz’s cancer was HER2-negative, while Trish’s was HER2-positive.
HER2-positive cancers are treated with drugs that specifically target the HER2 receptor on the outside of the breast cancer cell.
Herceptin (trastuzumab) is used to treat primary and secondary breast cancer. It is a monoclonal antibody (in other words, a large protein) that locks on to the HER2 protein and stops it working, which then stops the cancer cell from dividing and growing. Herceptin also helps the immune system attack and destroy breast cancer cells.
Perjeta (pertuzumab) is another monoclonal antibody that locks on to a different part of the HER2 protein. If you are having neoadjuvant chemotherapy you may be given Perjeta and Herceptin (a combination known as ‘dual anti-HER2 therapy’). Perjeta is also used to treat patients with secondary HER2-positive cancers.
Tyverb (lapatinib) locks on to the HER2 receptor and another epidermal growth factor receptor called HER1. It is currently only used to treat secondary HER2-positive breast cancer.
Kadcyla (trastuzumab emtansine) is a combination of two drugs. The first, trastuzumab (Herceptin) locks onto the HER2 receptor. This then allows targeted delivery of the second drug, emtansine, directly into cancer cells which destroys them. Normal cells are unharmed so there are fewer side effects than with chemotherapy. Kadcyla is currently only used to treat secondary HER2-positive breast cancer.
Herceptin, Perjeta and Kadcyla are given by injections – either into your vein or under your skin. Most patients have them as an out-patient in hospital (often on the chemo unit), but they may be given in your GP surgery or at home. Tyverb comes as a tablet that you take every day.
At the time of writing, Herceptin can only be given with a course of chemotherapy. This is because all the evidence showing the benefit of Herceptin comes from research trials where patients were given both chemotherapy and Herceptin at the same time. This means that even if you have a very small HER2-positive cancer that hasn’t spread to your lymph nodes, like Trish, you still need to have chemotherapy in order to get Herceptin treatment. Your oncologist may give you a gentler chemotherapy regime that is easier to tolerate, together with Herceptin, like Trish had. She was told to think of chemotherapy as a general poison that would make the cancer cells more susceptible to the ‘silver bullet’ of Herceptin.
Herceptin is currently given once every three weeks for a total of 18 doses, which takes a year. If you have neoadjuvant chemotherapy, you’ll have either Herceptin, or Herceptin and Perjeta (dual anti-HER2 therapy) at the same time. Once you’ve had surgery, you’ll continue with Herceptin alone.
You may have Herceptin, Herceptin and Perjeta, or Tyverb together with chemotherapy. Your oncologist will determine which drugs you need based on your tumour type and spread, and its response to previous treatment.
Herceptin cannot be given if you are pregnant or breastfeeding because it can damage your baby. You must use contraception during treatment and for at least six months after the date of your last Herceptin dose. If you have heart problems, you may not be able to have Herceptin because it can affect your heart (see here for more on this).
The first injection is slow, and can take 90 minutes to give. It is normally given in to a vein (via a cannula, PICC or port) at the same time as your chemotherapy infusion. You are given anti-allergy drugs (such as steroids) to take first to reduce the risk of an allergic reaction, and you have to stay in the hospital for several hours to make sure that you feel okay afterwards. If it’s given before chemo, the waiting time may have finished by the time your chemo drugs have been infused. The next injections are much shorter, and only take 30 minutes or so.
After your first dose, or once you have finished chemo, you can have your remaining treatments as an injection under the skin of your thigh, swapping sides each time. The first injection under the skin will be in the hospital and takes 3–5 minutes. You may then be able to have the remainder of your injections closer to home, instead of having to travel to the hospital.
Trish had Herceptin injected under the skin of her thigh. It didn’t really hurt, apart from the initial prick when the needle went in. Sometimes she gave the injection herself at home.
Most people tolerate Herceptin very well and side effects are relatively rare. You may feel like you have a mild dose of the flu for a day or two after the treatment (aching muscles, a sore throat, sickness, loss of appetite, diarrhoea and exhaustion), but this normally eases with paracetamol.
Trish didn’t get many side effects on Herceptin. She was able to go back to work straight after her injections, and even did an all-night charity bike ride the day after one of her treatments.
Around 1 in 20 people have an allergic reaction during or up to 6 hours after their first Herceptin treatment. If this happens, you will feel unwell. Your lips may swell, you may feel breathless and develop a rash. You may also have a headache, dizziness or joint and muscle pains. If you think you’re having an allergic reaction, tell your nurse immediately. If you’re at home, you should call the emergency number you were given. You will be given medication to control the reaction and may be kept in hospital overnight.
Like chemotherapy, HER2 treatment lowers your immune system which means you are more likely to develop a serious infection. We tell you how to reduce your chances of developing an infection here.
Herceptin, Perjeta and Tyverb can cause an abnormal heart rhythm or weaken a heart muscle called the left ventricle. This means your heart can’t pump blood as well as it did before, which can make you tired, breathless or feel like your heart is fluttering. This complication occurs in a mild form in up to 20 per cent of patients and can cause serious long-term heart problems in around 2 per cent. Heart damage from Herceptin is more likely if you already had heart problems before treatment, such as a very high blood pressure, or are diabetic or overweight, though it can occur in previously fit people.
Before you start Herceptin, you will have a heart scan (‘multiple-gated acquisition’ or MUGA scan) to monitor how well your heart pumps. It is very similar to having an ultrasound scan and doesn’t hurt. You lie on a couch while a doctor runs a probe over your chest to look at your heart muscle. It is repeated every 3–4 months throughout your treatment. If you do develop heart problems, these normally get better when Herceptin treatment stops, although a very small number of people are left with permanent heart damage.
Trish’s first heart scan showed a minor abnormality which was very alarming at the time. However, her oncologist reassured her that lots of healthy people have minor abnormalities found on heart scans which have no significance whatsoever. Her heart remained fine throughout her treatment, and this was confirmed with the repeated scans.
Perjeta can give you a sore mouth which can be treated with a mild mouthwash, such as Difflam, and you should brush your teeth with a soft baby toothbrush.
Perjeta can also cause anaemia (not enough red blood cells) which can make you feel tired, weak and dizzy. The anaemia normally gets better once your treatment stops, but you might need an injection to stimulate your bone marrow (see here) or a blood transfusion to help.
These are drugs given to patients with secondary breast cancer that target other specific proteins in (or on) cancer cells. They are used to complement chemotherapy drugs, which target all dividing cells. Some of them are only available as part of a research trial. New agents are being developed all the time, so this list may change in the future.
Palbociclib (Ibrance) and Ribociclib (Kisqali) block particular proteins called CDK4 and 6 enzymes. These affect cell growth and division. They are given to ER-positive patients, together with an Aromatase Inhibitor, and reduce the effects of oestrogen on cancer cells.
Everolimus (Afinitor) blocks a protein called mTOR which affects how cancer cells divide and grow. It is only given to patients with ER-positive secondary cancer resistant to hormonal therapy.
Bevacizumab (Avastin) interferes with how growing cancers develop their blood supply, and cuts off their supply of oxygen and food.
Targeted therapies are one of the most exciting new developments in the treatment of breast cancer, and we hope that in the future there will be even more drugs available to treat both primary and secondary breast cancer.