HER2-Positive Breast Cancer Targeted Therapies

HER2 is a protein that sits on the surface of cells and tells them to grow. In roughly one in five breast cancers, the gene for that protein is amplified, so the cell is covered in far too many copies and receives a constant instruction to divide. That is what your pathology report means when it says HER2-positive, IHC 3+, or FISH amplified.

The important part is what follows from it. Because the cancer depends on a specific protein, that protein can be targeted directly. HER2-positive disease is not treated with chemotherapy alone; it is treated with drugs designed to attach to HER2 and shut it down.

Trastuzumab was the first, and it changed the field. It is an antibody that binds HER2 and blocks its signal while flagging the cell for your immune system. It is usually given alongside chemotherapy and then continued on its own, most often to complete about a year of treatment in early-stage disease.

Pertuzumab binds a different part of the same protein and is frequently added to trastuzumab, because blocking two sites works better than blocking one. Many people receive both together with chemotherapy before surgery.

T-DM1, or ado-trastuzumab emtansine, is an antibody-drug conjugate: trastuzumab chemically linked to a chemotherapy payload, so the drug is carried directly to HER2-positive cells. It is commonly used after surgery when cancer is still found in the tissue removed, and in metastatic disease.

Trastuzumab deruxtecan is a newer conjugate with a different payload that has produced striking results in metastatic HER2-positive disease and also works in tumors with lower levels of HER2. Tucatinib, neratinib, lapatinib, and margetuximab fill other roles, including treatment that reaches disease in the brain.

Many of these are now available as under-the-skin injections that take minutes rather than an infusion that takes an hour.

HER2 is also present in heart muscle, so HER2-targeted drugs can reduce the heart's pumping strength. This is why you will have an echocardiogram or MUGA scan before starting and then repeated during treatment, often around every three months. What is being measured is your ejection fraction, the percentage of blood the left ventricle pushes out with each beat.

Most people's hearts tolerate treatment without difficulty. If the ejection fraction drops, treatment is usually paused, cardiology is involved, and heart medications may be started. Unlike anthracycline damage, trastuzumab-related decline is frequently reversible, and many people resume treatment afterward. Tell your team about new breathlessness, ankle swelling, a racing heart, or sudden difficulty with stairs rather than waiting for the next scan.

Not long ago, HER2-positive was among the worst things a pathology report could say. It marked a cancer that grew quickly, recurred often, and had few specific treatments. That is no longer the picture. Since targeted therapy arrived, outcomes for HER2-positive breast cancer have improved so substantially that it is now considered one of the more treatable subtypes, and a real proportion of people have no invasive cancer left in the tissue removed at surgery after pre-operative treatment.

Older survival statistics you find online may predate these drugs entirely. If a number frightens you, ask your oncologist which era of data it came from.

Day to day, treatment often feels less brutal than people expect. The chemotherapy months are usually the hard part; the antibody months that follow are frequently manageable, and many people work through them. Common effects include infusion reactions early on, diarrhea, fatigue, and a runny nose or cough. Fertility, pregnancy plans, and long-term heart health are all reasonable things to raise before you begin rather than afterward.

• NCI - Targeted Therapy to Treat Cancer
• NCI - Breast Cancer Information