What are the indications and treatment protocols for Trastuzumab (Herceptin) in breast cancer?

Trastuzumab Indications in Breast Cancer

Trastuzumab is indicated for HER2-positive breast cancer in both early-stage (adjuvant/neoadjuvant) and metastatic settings, with treatment protocols requiring HER2 testing to confirm overexpression (IHC 3+ or FISH amplification >2.0) before initiating therapy.

Patient Selection and HER2 Testing

• HER2 is overexpressed/amplified in 20-30% of human breast tumors and is associated with poor prognosis 1
• Patient selection must be based on FDA-approved companion diagnostic tests for HER2 2
• Recommended testing methods:
  • Immunohistochemistry (IHC): Patients with 3+ staining should receive trastuzumab
  • Fluorescence in situ hybridization (FISH): Patients with amplification ratio >2.0 should receive trastuzumab
  • Patients with IHC 0-1+ or FISH negative should not receive trastuzumab 1

Indications for Trastuzumab

1. Early-Stage Breast Cancer (Adjuvant Setting)

• Indicated for HER2-overexpressing node-positive or node-negative (ER/PR negative or with high-risk features) breast cancer 2
• Recommended for tumors >1 cm (Category 1 evidence) 1
• Should also be considered for tumors <1 cm, particularly in ER-negative disease 1
• Reduces recurrence risk by approximately 50%, providing 10% absolute improvement in DFS and 9% increase in 10-year OS 1, 3

2. Metastatic Breast Cancer

• Indicated in combination with paclitaxel for first-line treatment 2
• Indicated as a single agent for patients who have received one or more chemotherapy regimens for metastatic disease 2
• Continuation of HER2 blockade is recommended for patients with HER2-positive metastatic breast cancer that progresses on first-line trastuzumab-containing regimens 1

Treatment Protocols and Administration

Adjuvant Setting

• Standard duration: 1 year of treatment 1, 4
• Dosing options:
  • Loading dose: 8 mg/kg IV, followed by 6 mg/kg IV every 3 weeks 4
  • Alternative weekly schedule: 4 mg/kg IV loading, then 2 mg/kg IV weekly 4
• Preferred regimens:
  • AC followed by T + trastuzumab ± pertuzumab (doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab) 1
  • TCH (docetaxel/carboplatin/trastuzumab) ± pertuzumab 1

Metastatic Setting

• Trastuzumab in combination with selected chemotherapeutics or as a single agent is recommended for first-line therapy 1
• Effective combinations include:
  • Trastuzumab + paclitaxel (with or without carboplatin)
  • Trastuzumab + docetaxel
  • Trastuzumab + vinorelbine
  • Trastuzumab + capecitabine 1

Timing and Coordination with Other Treatments

• Trastuzumab should be started concurrently with the taxane portion of chemotherapy 1
• Should not be administered concurrently with anthracyclines due to cardiotoxicity risk 1, 4
• Can be administered concurrently with radiation therapy and endocrine therapy (if ER/PR positive) 4
• Should ideally begin within 2-6 weeks after surgery, as efficacy decreases when administered more than 12 weeks after surgery 4

Cardiac Monitoring and Safety

• Baseline cardiac assessment (LVEF measurement) is required before initiating trastuzumab 2
• Regular monitoring at 3,6, and 9 months during treatment is essential 4
• Major adverse effects:
  • Cardiotoxicity: Symptomatic or asymptomatic cardiac dysfunction occurred in 27% of patients receiving anthracycline + cyclophosphamide + trastuzumab 5
  • Infusion reactions: Fever, chills, and potential for anaphylaxis 2
  • Pulmonary toxicity 2

Special Considerations

• In neoadjuvant setting, trastuzumab should be started with the taxane part of chemotherapy to increase probability of pathologic complete response 1
• Trastuzumab should be completed for a total of 1 year of treatment regardless of whether given in neoadjuvant or adjuvant setting 4
• For patients with HER2-positive metastatic breast cancer that progresses on trastuzumab, options include:
  • Continuing trastuzumab with a different chemotherapy agent
  • Capecitabine plus lapatinib
  • Trastuzumab plus lapatinib 1

Trastuzumab has revolutionized the treatment of HER2-positive breast cancer, significantly improving survival outcomes in both early and metastatic settings when properly selected based on accurate HER2 testing.