Trastuzumab

Trastuzumab binds HER2 on tumors with high HER2 expression or gene amplification, blocks growth signaling, and recruits immune effector mechanisms; cardiac safety and accurate HER2 testing are central to its use.

Trastuzumab binds the extracellular domain of the HER2 receptor. It inhibits HER2-mediated signaling and can promote antibody-dependent cellular cytotoxicity, in which immune cells attack antibody-coated tumor cells. It may also reduce receptor shedding and alter downstream signaling. [T1, T2]

HER2 is encoded by ERBB2. Tumors driven by HER2 amplification or marked overexpression are more likely to depend on this pathway. Trastuzumab is not cytotoxic chemotherapy, but it is commonly administered with chemotherapy or other HER2-directed agents. [T1, T2]

The current U.S. Herceptin label includes HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal-junction adenocarcinoma. Other trastuzumab-containing products, combinations, and antibody-drug conjugates have separate labels and should not be merged into this page. [T1]

Adjuvant treatment of selected HER2-overexpressing, node-positive or high-risk node-negative breast cancer in specified chemotherapy sequences or after multimodality therapy. [T1, T4]

First-line treatment of HER2-overexpressing metastatic breast cancer in combination with paclitaxel. [T1]

Single-agent treatment of HER2-overexpressing metastatic breast cancer after one or more prior chemotherapy regimens. [T1]

In combination with cisplatin and capecitabine or fluorouracil for previously untreated HER2-overexpressing metastatic gastric or GEJ adenocarcinoma. [T1, T5]

Patient selection requires HER2 protein overexpression or ERBB2 gene amplification in a tumor specimen using an FDA-authorized or otherwise validated assay appropriate for the cancer type. Breast and gastric scoring systems are not identical. [T1, T3]

Immunohistochemistry (IHC) measures HER2 protein expression. [T1, T3]

In situ hybridization (ISH/FISH and related methods) measures ERBB2 gene amplification. [T1, T3]

Equivocal or discordant results may require repeat or alternative testing according to tumor-specific guidelines. [T3]

HER2 heterogeneity is especially relevant in gastric cancer and after treatment. A prior positive result may not perfectly represent a later metastatic site. "HER2-low" is a treatment category used for certain antibody-drug conjugates; it does not automatically meet the HER2-overexpression requirement for conventional trastuzumab. [T1, T3]

Herceptin is administered by intravenous infusion. Trastuzumab and hyaluronidase-oysk is a separate subcutaneous product with its own formulation and label. Biosimilars are highly similar to the reference biologic but should be displayed with their exact nonproprietary and brand names. This document does not provide infusion schedules or preparation instructions. [T1, T2, T9]

Common adverse effects depend strongly on the chemotherapy partner and cancer type. Label-reported effects include infusion-related fever and chills, headache, nausea, diarrhea, fatigue, infection, cough, rash, and cytopenias. In gastric-cancer combinations, neutropenia, anemia, thrombocytopenia, stomatitis, weight loss, and taste changes may reflect the entire regimen. [T1]

Cardiomyopathy and reduced LVEF, including congestive heart failure. Risk can be higher with anthracyclines and in people with cardiac disease. [T1]

Severe or fatal infusion reactions, including anaphylaxis and respiratory distress. [T1]

Pulmonary toxicity, including pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, and acute respiratory distress syndrome. [T1]

Embryo-fetal toxicity, particularly oligohydramnios and related fetal complications. [T1]

Worsening chemotherapy-induced neutropenia in some combination regimens. [T1]

LVEF before treatment and at regular intervals during therapy; more frequent reassessment if treatment is withheld for cardiac dysfunction. [T1]

Clinical signs of heart failure: shortness of breath, edema, rapid weight gain, orthopnea, cough, or reduced exercise tolerance. [T1]

Infusion reactions during and after administration, with appropriate emergency support available. [T1]

Pregnancy status and contraception counseling. [T1]

Blood counts and organ-function monitoring required by the accompanying chemotherapy regimen. [T1]

The most important interaction is overlapping cardiotoxicity. Anthracyclines administered during trastuzumab treatment or soon after it can increase cardiac risk because trastuzumab has a long washout period. Other combination partners add marrow, pulmonary, neurologic, or gastrointestinal toxicity. The sequence and timing of HER2-directed therapies must be managed by the oncology team. [T1]

Treatment should be based on reliable HER2 testing; false-positive results expose patients to toxicity without expected benefit, while false-negative results may deny effective therapy. [T1, T3]

Trastuzumab is not interchangeable with ado-trastuzumab emtansine, trastuzumab deruxtecan, trastuzumab-hyaluronidase, or pertuzumab/trastuzumab co-formulations. [T2]

Pre-existing heart disease or a clinically important fall in LVEF may require interruption, discontinuation, or an alternative strategy. [T1]

HER2 positivity predicts potential benefit, not guaranteed response; resistance and tumor heterogeneity remain important. [T6]

The current Herceptin U.S. label does not broadly cover every HER2-expressing cancer or HER2-low disease. [T1]

Proposed resistance mechanisms include loss or heterogeneity of HER2 expression, truncated HER2 forms, impaired antibody binding, activation of PI3K-AKT signaling through PIK3CA mutation or PTEN loss, signaling through alternative receptors, changes in immune effector function, and downstream pathway reactivation. These mechanisms can coexist and may differ between breast and gastric cancers. [T6]

Repeat HER2 testing can be clinically relevant after progression because HER2 status may change. However, no single resistance assay universally determines the next therapy. [T3, T6]

Long-term HERA follow-up established durable benefit of one year of adjuvant trastuzumab in HER2-positive early breast cancer while also defining long-term cardiac considerations. [T4]

The ToGA trial established trastuzumab plus chemotherapy in HER2-positive advanced gastric/GEJ cancer. [T5]

The APT study and follow-up supported a less intensive paclitaxel-trastuzumab strategy for selected small, node-negative HER2-positive breast cancers, illustrating risk-adapted de-escalation. [T7]

Current research focuses on shorter or chemotherapy-sparing regimens for selected early disease, biomarkers of cardiotoxicity and resistance, and sequencing of newer HER2-directed antibodies and antibody-drug conjugates. Those newer agents are separate medicines, not simply "stronger trastuzumab." [T6, T8]

Regulatory indications and safety language are summarized primarily from U.S. FDA prescribing information. Approval status, testing requirements, formulations, and recommended use may differ in other countries or change after this document is published.