Trastuzumab is a lab-made antibody that attaches to a protein called HER2 on the surface of cancer cells, blocking the signals that tell those cells to grow and divide. It also flags those cells for destruction by the immune system. This dual action makes it one of the most effective targeted therapies for cancers that produce too much HER2, particularly breast cancer and certain stomach cancers.
What HER2 Does in Cancer
HER2 (human epidermal growth factor receptor 2) is a protein that sits on the surface of cells and helps regulate normal growth. Every healthy cell has a small number of HER2 receptors. But in roughly 15 to 20 percent of breast cancers and a subset of gastric cancers, the gene that codes for HER2 goes into overdrive, producing far more copies of the protein than normal. When the cell surface is crowded with HER2 receptors, growth signals fire constantly, pushing the cell to divide rapidly and resist the normal signals that would tell it to stop or die.
This is what oncologists mean by “HER2-positive” cancer. Before targeted therapies existed, HER2-positive breast cancer carried a worse prognosis than HER2-negative disease. Trastuzumab changed that outlook dramatically when it was introduced in the late 1990s.
How Trastuzumab Blocks Growth Signals
Trastuzumab works by binding to a specific region on the outside of the HER2 protein known as domain IV. This is a critical part of the receptor involved in activation. When trastuzumab locks onto domain IV, it physically prevents HER2 from switching on and sending growth signals into the cell’s interior.
Without those signals, several downstream chain reactions inside the cell are disrupted. The pathways that normally drive cell division, prevent programmed cell death, and promote blood vessel growth to feed the tumor all slow down or stop. In practical terms, this means the cancer cells lose their main engine of unchecked growth.
Trastuzumab also appears to prevent the outer portion of HER2 from being clipped off the cell surface, a process called shedding. When shedding occurs, the remaining stub of the receptor can become permanently active, which is harder to treat. By keeping the receptor intact, trastuzumab maintains its own ability to stay bound and keep signaling suppressed.
How It Recruits the Immune System
Blocking growth signals is only half the story. Trastuzumab is built on the backbone of a human IgG1 antibody, and the tail end of that antibody (the Fc region) serves as a beacon for immune cells. When trastuzumab coats a cancer cell, immune cells recognize that Fc tail through receptors on their own surface and attack.
The most important immune players in this process are natural killer (NK) cells. NK cells carry a receptor called CD16 that recognizes antibody-coated targets. Once an NK cell locks on, it releases granules filled with proteins called perforins and granzymes. Perforins punch holes in the cancer cell’s membrane, and granzymes enter through those holes to trigger cell death from the inside. This entire process is called antibody-dependent cellular cytotoxicity, or ADCC.
NK cells aren’t the only participants. Monocytes, macrophages, dendritic cells, and certain white blood cells called granulocytes can also recognize the Fc tail and contribute to tumor destruction. Together, these immune mechanisms mean that trastuzumab doesn’t just slow cancer growth; it actively helps the body destroy cancer cells.
Which Cancers It Treats
Trastuzumab is FDA-approved for HER2-positive breast cancer in both early-stage and metastatic settings. It is also approved for metastatic stomach cancer and cancers at the junction between the stomach and esophagus, as long as the tumor overexpresses HER2.
Not every cancer with some HER2 qualifies. Tumors are tested using two main methods: a protein stain (immunohistochemistry, or IHC) that scores the amount of HER2 on the cell surface from 0 to 3+, and a genetic test (FISH) that checks whether the HER2 gene itself is amplified. A score of IHC 3+ or a positive FISH result typically qualifies a patient for trastuzumab. An IHC 2+ score is considered borderline and requires follow-up genetic testing to confirm. Importantly, testing methods differ between breast and stomach cancers because HER2 expression patterns look different in stomach tissue, with more patchy, incomplete staining.
What Happens During Treatment
Trastuzumab is given as an intravenous infusion. The first dose is larger (a loading dose) to build up drug levels in the body quickly. After that, smaller maintenance doses follow on either a weekly or every-three-week schedule, depending on the treatment plan. The drug has a half-life of roughly 6 days at standard doses, though this varies widely between patients (from about 1 to 32 days in clinical studies). That relatively long half-life is what allows it to be given on a weekly or tri-weekly basis rather than daily.
Treatment duration depends on the cancer stage. In early-stage breast cancer, a standard course lasts about one year. In metastatic disease, treatment often continues as long as it keeps working and side effects remain manageable.
Heart Monitoring During Treatment
The most notable side effect of trastuzumab is its potential impact on the heart. Unlike the permanent heart damage that certain chemotherapy drugs can cause, trastuzumab-related heart effects are often reversible, but they still require careful monitoring.
Heart function is tracked using a measurement called the left ventricular ejection fraction (LVEF), which reflects how well the heart pumps blood with each beat. Baseline heart function is assessed before treatment starts, then rechecked at roughly three-month intervals throughout therapy. Treatment is paused if LVEF drops by 10 percentage points or more to below the normal range, or by 16 or more percentage points from baseline regardless of absolute value. If heart function recovers sufficiently, treatment can resume. If it doesn’t, trastuzumab is stopped permanently.
Why Some Tumors Stop Responding
Despite its effectiveness, some HER2-positive cancers either don’t respond to trastuzumab from the start or develop resistance over time. Several biological mechanisms explain this.
One major route involves a truncated version of the HER2 protein called p95-HER2. This shortened form lacks the outer domain where trastuzumab binds, so the drug simply has no place to attach. The receptor’s internal signaling machinery, however, remains active. Tumors that produce a lot of p95-HER2 tend to respond poorly to trastuzumab.
Another common escape route involves the PI3K-AKT signaling pathway, a separate growth circuit inside the cell. Mutations in a gene called PIK3CA can switch this pathway on independently, bypassing HER2 entirely. Research shows that PIK3CA mutations frequently coexist with HER2 amplification, meaning the cell has a backup engine even when HER2 is shut down. Newer drug combinations and next-generation HER2-targeted therapies have been developed in part to address these resistance mechanisms.
Biosimilar Versions
The original brand-name product, Herceptin, is no longer the only option. Six trastuzumab biosimilars have been approved in the United States, starting with the first in December 2017. Biosimilars are rigorously tested to confirm they work the same way as the original drug, with no clinically meaningful differences in safety or effectiveness. Their availability has expanded access and reduced treatment costs for many patients. Your oncology team will choose whichever version is available at your treatment center, and you can expect the same therapeutic benefit regardless of which one is used.