Trastuzumab is approved for HER2-positive breast cancer

One protein, one antibody

On September 25, 1998, the FDA approved trastuzumab. The letter went to Genentech. It named two uses, both in metastatic breast cancer whose tumors overexpress the HER2 protein. One was for people who had already had chemotherapy for metastatic disease. The other paired the drug with paclitaxel for people who had not.

The drug was marketed as Herceptin. What made it a landmark was not how well it worked. It was how it decided whom to work on.

What HER2 actually is

HER2 stands for human epidermal growth factor receptor 2. It is a protein that sits on the surface of cells and passes along growth signals.

Some breast cancers make far too much of it. The cells are then pushed to divide faster than they should. Doctors call this HER2 overexpression, and a tumor with it is called HER2-positive.

Trastuzumab is a monoclonal antibody. FDA's 1998 label describes it as binding with high affinity to the outer part of the HER2 protein. It also notes that the drug helps immune cells attack HER2-heavy cancer cells. A tumor without extra HER2 gives the antibody nothing to grab.

This is why the approval mattered. The drug arrived with a test attached. You did not give it to everyone with breast cancer. You gave it to the group whose tumors carried the target. Our page on biomarker testing explains how that idea works today.

The numbers behind the approval

The main study was a phase 3 trial in first-line treatment. People got chemotherapy alone, or chemotherapy plus trastuzumab.

The primary measure was time to progression, meaning how long before the cancer grew again. The median was 7.2 months with trastuzumab added, against 4.5 months with chemotherapy alone. The label reports that difference at p less than 0.0001. The label also states that adding trastuzumab produced a higher response rate, longer responses, and a higher one-year survival rate.

In a separate study of people already treated with chemotherapy, trastuzumab was given alone. An independent committee put the overall response rate at 14 percent, with 2 percent complete and 12 percent partial responses.

Those are modest-looking figures. In 1998, for metastatic disease, they were not.

The warning printed at the top

The 1998 label opened with a boxed warning about cardiomyopathy, which means damage to the heart muscle. It stated that trastuzumab can cause ventricular dysfunction and congestive heart failure.

The label told doctors to check left ventricular function before and during treatment, and to strongly consider stopping the drug if heart function drops in a meaningful way. It also flagged that the problem was worst when trastuzumab was combined with anthracyclines and cyclophosphamide.

Heart monitoring during HER2-targeted treatment traces directly back to this page of text.

From last resort to standard care

The 1998 approval covered metastatic disease only. That changed.

On November 16, 2006, FDA approved trastuzumab as part of an adjuvant regimen with doxorubicin, cyclophosphamide, and paclitaxel, for HER2-positive, node-positive breast cancer. Adjuvant means given after surgery to lower the chance the cancer returns. That shift moved the drug from the end of the road to the start of it.

Who this affects

HER2-positive disease is a minority of breast cancer. In SEER data, about 9.3 percent of cases are hormone-receptor-positive and HER2-positive, and about 4.0 percent are hormone-receptor-negative and HER2-positive. That is roughly one in eight.

Five-year relative survival in SEER is 92.2 percent for the first group and 87.0 percent for the second, measured in people diagnosed between 2016 and 2022. Across all breast cancer, that survival figure is 91.9 percent. The count for the year ahead is not an NCI measurement: ACS estimates 321,910 new cases in the United States for 2026, and SEER republishes the estimate. These are group figures from thousands of people. They describe no individual.

When to have a breast change checked

Do not wait for a scheduled mammogram if you notice any of these:

• a new lump or thickening in the breast or underarm.
• a change in the size or shape of one breast.
• skin that dimples, puckers, or looks like orange peel.
• a nipple that turns inward, or discharge that is bloody or comes without squeezing.
• redness, scaling, or a rash on the nipple or breast skin.

Most of these turn out to be benign. They still need to be examined rather than watched at home. Our guide to breast cancer symptoms goes into what happens at that appointment, and our breast cancer overview covers the disease as a whole.

What this approval cannot tell you

• The 1998 result was measured in months of delay before progression. It was not a claim that the cancer was gone.
• The trial enrolled people with HER2 overexpression measured by the assays of the day. Testing methods have changed since.
• Nothing here applies to HER2-negative breast cancer, which is most breast cancer.
• Labels change. The current prescribing information, not this page, is what governs use.

Sources

• FDA approval letter, trastuzumab, September 25, 1998
• FDA prescribing information, HERCEPTIN, 1998
• FDA approval letter, adjuvant indication, November 16, 2006
• SEER Cancer Stat Facts: Female Breast Cancer
• SEER Cancer Stat Facts: Female Breast Cancer Subtypes

How this page was made

An AI-assisted editorial system helped prepare this page. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown. Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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