HER2-Positive and HER2-Low Breast Cancer Care

This page is for people whose breast cancer pathology report mentions HER2. It explains how HER2 is measured, what HER2-positive and HER2-low mean, and how each affects treatment options.

HER2 is a protein on the surface of breast cells. It signals them to grow. Some breast cancers make far too much of it. Testing usually starts with immunohistochemistry (IHC), a stain that shows which proteins a cell is making. IHC scores staining from 0 to 3+. Unclear results, scored 2+, go on to an in situ hybridization test such as FISH. That test counts copies of the HER2 gene.

For two decades the result was yes or no. IHC 3+, or IHC 2+ with a positive FISH, meant HER2-positive. That gave access to HER2-targeted drugs. Everything else was HER2-negative and got none of them.

That split no longer holds. Trastuzumab deruxtecan is an antibody-drug conjugate. It carries chemotherapy to cells with even modest HER2 on their surface. It turned out to work in tumors that were never considered HER2-positive.

On August 5, 2022, the FDA approved trastuzumab deruxtecan for unresectable or metastatic HER2-low breast cancer, in people who had already had chemotherapy for metastatic disease, or whose cancer came back during or within 6 months of chemotherapy after surgery. It defined HER2-low as "IHC 1+ or IHC 2+/ISH-." The DESTINY-Breast04 trial gave the figures. In the hormone receptor-positive group, median progression-free survival was 10.1 months with trastuzumab deruxtecan. It was 5.4 months with the physician's choice of chemotherapy. Median overall survival was 23.9 versus 17.5 months.

In January 2025 the FDA extended this further, to HER2-ultralow disease. That means IHC 0 with some membrane staining. The approval covers hormone receptor-positive metastatic breast cancer that has grown after one or more endocrine therapies. It covers HER2-low disease in this group too, without prior chemotherapy for metastatic disease being required. In the DESTINY-Breast06 trial behind it, median progression-free survival in the HER2-low group was 13.2 months with trastuzumab deruxtecan and 8.1 months with chemotherapy.

Here is the practical consequence. Before 2022, IHC 0 and IHC 1+ were both treated as HER2-negative. So pathology reports often said only "HER2-negative" without recording which. NCI also notes that pathologists did not always agree when telling HER2-low apart from HER2-0.

Now it does. Your report may predate these approvals, or say only "negative." If so, it is reasonable to ask whether the original slides can be reviewed. You can also ask whether a newer biopsy, such as one from a site of spread, should be tested.

HER2-low came into use as a category because a drug turned out to work there. That helps explain why the definition has kept moving.

HER2-positive disease has a deep toolbox. Trastuzumab and pertuzumab are antibodies given with chemotherapy. In early-stage disease they are often given before surgery. Ado-trastuzumab emtansine and trastuzumab deruxtecan are antibody-drug conjugates. Tucatinib, neratinib, and lapatinib are oral drugs that block HER2 signaling inside the cell. In the HER2CLIMB trial of tucatinib, people with and without cancer in the brain both benefited. Margetuximab is another antibody option, approved after two or more earlier anti-HER2 treatments.

The American Cancer Society says HER2-positive cancers tend to grow and spread faster than HER2-negative ones, but are much more likely to respond to drugs that target HER2.

HER2-low is used to decide who can get certain treatments for metastatic disease. It is not used to predict outlook. NCI says about 50 to 60 percent of breast cancers fall into it. Hormone receptor status still shapes most of the treatment order. For hormone receptor-positive cancer, the FDA approvals place trastuzumab deruxtecan after at least one endocrine therapy. HER2-low does not qualify someone for trastuzumab and pertuzumab. Those are for HER2-positive cancer.

Trastuzumab deruxtecan carries a boxed warning for interstitial lung disease and embryo-fetal toxicity. Its label says new or worsening cough, shortness of breath, or fever should be reported right away, not saved for the next visit.

• What is my exact IHC score and any FISH ratio, not just positive or negative?
• Was my most recent biopsy tested, or only my original one?
• How does HER2-low affect the order of my options?

• Call 911 or go to an emergency department if you are suddenly fighting for breath at rest, or your lips or fingertips turn blue or grey.
• Get seen the same evening, not the next morning, if your temperature reaches 100.4°F (38°C) or higher while you are on treatment. CDC calls a fever during chemotherapy a medical emergency. Ring the oncology line first if you can, and if nobody answers within minutes, go to an emergency department and say you are on cancer treatment.
• Call your care team right away if you are receiving trastuzumab deruxtecan and a cough appears, or breathing gets harder doing things you managed last week. The drug's label asks for cough, breathlessness and fever to be reported immediately, because they can be the first sign of lung inflammation.

• NCI: Breast Cancer Treatment (PDQ) - Patient Version
• DailyMed: ENHERTU (fam-trastuzumab deruxtecan-nxki) label
• CDC: Fever and Cancer Treatment
• NCI: Drugs approved for breast cancer
• NCI: Targeted therapy to treat cancer
• NCI Dictionary of Cancer Terms
• FDA: Trastuzumab deruxtecan for HR-positive, HER2-low or HER2-ultralow breast cancer (2025)
• NCI Cancer Currents: Trastuzumab Deruxtecan for Metastatic HER2-Low Breast Cancer
• NCI: Breast Cancer Treatment (PDQ) - Health Professional Version
• American Cancer Society: Breast Cancer HER2 Status