Trastuzumab Indications
Trastuzumab (Herceptin) is a humanized monoclonal antibody used to treat HER2-positive breast cancer and HER2-positive metastatic gastric cancer by targeting the HER2 receptor, which is overexpressed in approximately 15-30% of breast cancers and associated with aggressive tumor behavior. 1, 2
Primary Indications
HER2-Positive Breast Cancer
Early-Stage Disease (Adjuvant Treatment)
- Trastuzumab is indicated for adjuvant treatment of HER2-positive early breast cancer in patients with node-positive disease or node-negative tumors ≥1 cm, where it reduces the 3-year risk of recurrence by approximately 50% and reduces mortality by one-third. 1, 3
- The optimal treatment duration is 1 year, administered concurrently with paclitaxel as part of chemotherapy regimens. 1, 4, 5
Metastatic Disease
- Trastuzumab is approved as first-line therapy in combination with paclitaxel or docetaxel for HER2-positive metastatic breast cancer, where it significantly improves response rates, time to disease progression, duration of response, and overall survival compared to chemotherapy alone. 1, 6, 7
- As monotherapy, trastuzumab is indicated for second- or third-line treatment in patients who have previously received chemotherapy for metastatic disease, producing objective responses in 15-26% of patients. 7, 8
HER2-Positive Metastatic Gastric Cancer
- Trastuzumab is indicated for treatment of HER2-positive metastatic gastric cancer in combination with chemotherapy. 9
Patient Selection Criteria
HER2 Testing Requirements
- Patients must have HER2 protein overexpression or gene amplification confirmed by validated testing methods. 1, 4, 5
- HER2-positive status is defined as either IHC 3+ or FISH ratio >2.0. 4, 5, 2
- Patients with IHC 2+ should undergo FISH testing, as only 24% of IHC 2+ tumors have gene amplification and benefit from trastuzumab. 1
- HER2-low breast cancer (IHC 1+ or 2+ without amplification) does not benefit from trastuzumab therapy. 2
Mechanism of Action
- Trastuzumab binds with high affinity to the extracellular domain of the HER2 receptor, inhibiting ligand-dependent dimerization and downstream signaling pathways that promote tumor cell proliferation. 2, 9
- The antibody mediates antibody-dependent cellular cytotoxicity (ADCC), preferentially targeting HER2-overexpressing cancer cells. 2, 9
Recommended Treatment Regimens
Preferred Adjuvant Regimens for Early-Stage Disease
- AC (doxorubicin/cyclophosphamide) followed by paclitaxel plus trastuzumab ± pertuzumab 1, 4
- TCH (docetaxel/carboplatin/trastuzumab) ± pertuzumab 1, 4
- Paclitaxel plus trastuzumab for low-risk stage I disease, particularly in patients with comorbidities 1, 5
Critical Safety Considerations
Cardiac Toxicity
- Concurrent use of trastuzumab with anthracyclines should be avoided due to significant cardiac toxicity risk (27% incidence of symptomatic or asymptomatic cardiac dysfunction). 1, 7
- Trastuzumab-induced cardiotoxicity differs from anthracycline toxicity—it does not cause myocyte loss and is generally reversible upon discontinuation. 2
- Cardiac dysfunction occurs in 13% of patients receiving trastuzumab plus paclitaxel and 4.7% with trastuzumab monotherapy. 7
- Trastuzumab should be administered after completion of anthracycline-based chemotherapy, not concurrently. 1, 2