What Is HER2? A Patient's Guide

## What Is HER2? **HER2 (Human Epidermal Growth Factor Receptor 2)** is a protein found on the surface of cells that helps regulate cell growth. In normal cells, HER2 plays a controlled role in growth and repair. In some cancers, the gene that codes for HER2 is **amplified** (extra copies are made) or the protein is **overexpressed** (too much is produced). When this happens, the cancer cell gets a constant "grow and divide" signal — driving aggressive tumor growth. ## Which Cancers Can Be HER2-Positive? - **Breast cancer:** ~15–20% of breast cancers are HER2-positive; historically more aggressive, but now highly treatable - **Gastric / gastroesophageal junction cancer:** ~10–15% are HER2-positive - **Bladder cancer:** ~5–10% - **Colorectal cancer:** ~2–5% (emerging target) - **Lung adenocarcinoma:** HER2 mutations (different from amplification) occur in ~3–4% - **Other cancers:** biliary, endometrial, ovarian — increasingly being tested ## How HER2 Is Tested **Immunohistochemistry (IHC)** — measures how much HER2 protein is on the cell surface, scored 0 to 3+: - **0 or 1+:** HER2 negative (or HER2-low — see below) - **2+:** Equivocal — needs confirmation with FISH - **3+:** HER2 positive **FISH (Fluorescence In Situ Hybridization)** — counts the number of HER2 gene copies to confirm amplification when IHC is 2+. ## HER2-Low: A New Category In 2022, **HER2-low** (IHC 1+ or IHC 2+/FISH negative) became clinically relevant in breast cancer after the approval of **trastuzumab deruxtecan (T-DXd / Enhertu)**. This drug works in HER2-low patients who were previously considered HER2 negative. If you have breast cancer, ask whether you are HER2-low. ## HER2-Targeted Treatments Being HER2-positive opens access to highly effective targeted therapies: | Drug | Type | Used In | |---|---|---| | Trastuzumab (Herceptin) | Monoclonal antibody | Breast, gastric | | Pertuzumab (Perjeta) | Monoclonal antibody | Breast (with trastuzumab) | | T-DM1 / ado-trastuzumab emtansine (Kadcyla) | Antibody-drug conjugate | Breast | | T-DXd / trastuzumab deruxtecan (Enhertu) | Antibody-drug conjugate | Breast (HER2+ and HER2-low), gastric, lung | | Lapatinib (Tykerb) | Small molecule kinase inhibitor | Breast | | Tucatinib (Tukysa) | Kinase inhibitor | Breast (especially brain metastases) | | Neratinib (Nerlynx) | Kinase inhibitor | Breast (extended adjuvant) | ## What HER2-Positive Means for Your Treatment HER2-positive cancers were once considered more aggressive and harder to treat. The development of HER2-targeted therapies has transformed outcomes: - **Early HER2+ breast cancer:** Highly curable with surgery + chemotherapy + targeted antibodies - **Metastatic HER2+ breast cancer:** Median survival has improved from ~2 years to 5+ years with sequential targeted therapies