HER2-Positive Breast Cancer

What does HER2-positive mean?

HER2 (human epidermal growth factor receptor 2) is a protein that promotes the growth of cells. In around 15–20% of breast cancers, cancer cells produce too much HER2 protein — a process called HER2 overexpression, caused by amplification (extra copies) of the HER2 gene. HER2-positive tumours tend to grow faster and spread more readily than HER2-negative tumours. Before targeted therapies existed, HER2-positive breast cancer carried a worse prognosis. Today, with modern targeted treatments, it is one of the most treatable forms of breast cancer.

How is HER2 status tested?

HER2 status is determined from a biopsy sample. Two laboratory tests are used: immunohistochemistry (IHC), which measures the amount of HER2 protein on the surface of cancer cells (scored 0, 1+, 2+ or 3+), and fluorescence in situ hybridisation (FISH), which measures the number of HER2 gene copies. Results are classified as HER2-positive (IHC 3+, or IHC 2+ confirmed by FISH amplification), HER2-low (IHC 1+ or IHC 2+ without gene amplification), or HER2-negative (IHC 0).

Targeted treatments for HER2-positive breast cancer

HER2-positive breast cancer is treated with drugs that specifically target cells expressing the HER2 protein, leaving most healthy cells unaffected. The main targeted therapies are:

• Trastuzumab (Herceptin): The original HER2-targeted therapy. Given by intravenous infusion alongside chemotherapy for early and advanced HER2-positive breast cancer. Standard treatment for over 25 years.
• Pertuzumab (Perjeta): Often combined with trastuzumab for high-risk early breast cancer and metastatic disease. The combination (dual HER2 blockade) is now the standard of care.
• Ado-trastuzumab emtansine (T-DM1 / Kadcyla): An antibody-drug conjugate. Used for early HER2-positive breast cancer with residual disease after neoadjuvant treatment.
• Trastuzumab deruxtecan (T-DXd / Enhertu): A newer antibody-drug conjugate approved for HER2-positive and HER2-low metastatic breast cancer. Has significantly improved survival in advanced disease.
• Tucatinib (Tukysa) and lapatinib: Oral tyrosine kinase inhibitors. Particularly useful when breast cancer has spread to the brain.
• Neratinib (Nerlynx): An oral extended adjuvant therapy for early-stage ER-positive/HER2-positive breast cancer taken after one year of trastuzumab.

Prognosis and survival

Before targeted therapies, HER2-positive breast cancer had a significantly worse prognosis than HER2-negative disease. Modern treatments have transformed this. For early-stage HER2-positive breast cancer, five-year survival now exceeds 90% when treated with surgery, chemotherapy and targeted therapy. For metastatic HER2-positive disease, median overall survival has improved from under 18 months in the late 1990s to over 4–5 years with modern regimens — and continues to improve with new drugs.

HER2-positive and hormone receptor-positive breast cancer

Around 50% of HER2-positive breast cancers are also hormone receptor-positive (ER+ or PR+). These tumours are driven by both HER2 overexpression and oestrogen. Treatment combines targeted HER2 therapy, chemotherapy and endocrine therapy (tamoxifen or an aromatase inhibitor), typically continued for 5–10 years after completing chemotherapy and targeted therapy.

What is HER2-low breast cancer?

HER2-low is a newly recognised category (clinically relevant since 2022) for breast cancers that express a small amount of HER2 — more than zero (IHC 1+ or 2+/FISH-negative), but not enough to be classified as HER2-positive (IHC 3+). It accounts for approximately 55–60% of all breast cancers. The distinction has become clinically important because trastuzumab deruxtecan (Enhertu) specifically targets HER2-low tumours and has significantly improved outcomes in metastatic HER2-low disease, opening a new treatment pathway for a large group of patients.