What is the recommended treatment protocol for Trastuzumab (Herceptin) in patients with HER2-positive breast cancer?

Trastuzumab Treatment Protocol for HER2-Positive Breast Cancer

First-Line Treatment for Metastatic/Advanced Disease

For patients with HER2-positive metastatic breast cancer, the combination of trastuzumab, pertuzumab, and a taxane should be used as first-line treatment unless contraindications to taxanes exist. 1

• The preferred first-line regimen is trastuzumab plus pertuzumab plus docetaxel (Category 1 recommendation), or trastuzumab plus pertuzumab plus paclitaxel (Category 2A recommendation). 1
• This dual HER2 blockade approach is strongly recommended based on high-quality evidence demonstrating superior progression-free survival. 1
• Trastuzumab should be offered early to all HER2-positive metastatic breast cancer patients, with or without chemotherapy. 1

Dosing for metastatic disease:

• Trastuzumab: 8 mg/kg IV loading dose, then 6 mg/kg IV every 3 weeks. 1
• Alternative weekly dosing: 4 mg/kg IV loading dose, then 2 mg/kg IV weekly. 1
• Pertuzumab: standard dosing per protocol when combined with trastuzumab. 1

Adjuvant Treatment for Early-Stage Disease

For HER2-positive early breast cancer, trastuzumab should be administered for a total duration of 1 year (52 weeks) in combination with chemotherapy. 2, 3, 4

• The standard regimen is doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab (AC → paclitaxel + trastuzumab). 4
• Trastuzumab is initiated at 4 mg/kg on the day paclitaxel begins, then 2 mg/kg weekly for 52 weeks total. 4
• Alternative regimen: docetaxel/carboplatin/trastuzumab (TCH) for 6 cycles, avoiding anthracycline cardiotoxicity. 4

For node-positive disease:

• Add pertuzumab to trastuzumab plus taxane (dual HER2 blockade provides 24% relative risk reduction in recurrence). 2
• Pertuzumab is NOT routinely recommended for node-negative disease—it is reserved for node-positive patients only. 3

For tumors >1 cm, regardless of nodal status:

• One year of trastuzumab is indicated (Category 1 recommendation). 3

Treatment Sequencing and Duration

Chemotherapy should continue for 4-6 months or to maximal response, then stop chemotherapy while continuing HER2-targeted therapy until progression. 1

• When chemotherapy is discontinued, trastuzumab continues as monotherapy to complete the full 52-week course. 1, 2
• The 1-year duration is superior to shorter schedules: meta-analysis shows shorter durations result in worse disease-free survival (HR = 1.13, p = 0.01) and overall survival (HR = 1.16, p = 0.03). 5
• Extending trastuzumab beyond 1 year (to 2 years) provides no additional benefit. 4

For hormone receptor-positive disease:

• Endocrine therapy should be started AFTER completing all chemotherapy, not concurrently. 2, 3
• Endocrine therapy can be given concurrently with trastuzumab/pertuzumab. 2, 3
• Premenopausal women: tamoxifen for 5-10 years; postmenopausal women: aromatase inhibitor for 5-10 years. 3

Treatment After Disease Progression

If disease progresses during or after first-line trastuzumab-based therapy, continue HER2-targeted therapy with a different chemotherapy regimen. 1

• Second-line treatment: trastuzumab deruxtecan (T-Dxd) is the preferred option if not previously received. 1
• Alternative second-line option: trastuzumab-emtansine (T-DM1) demonstrated superior progression-free survival (9.6 vs 6.4 months) and overall survival compared to lapatinib plus capecitabine. 1
• Retrospective data and the Trial Beyond Progression show that continuing trastuzumab beyond first progression with a different chemotherapy regimen is superior to discontinuing trastuzumab. 1

For recurrence after adjuvant therapy:

• If recurrence occurs ≤12 months after completing adjuvant trastuzumab: follow second-line recommendations (T-Dxd or T-DM1). 1, 2
• If recurrence occurs >12 months after completing adjuvant trastuzumab: restart first-line therapy (trastuzumab, pertuzumab, taxane). 1, 2

Cardiac Monitoring Requirements

Cardiac function must be evaluated before treatment initiation, every 3 months during therapy, and after completion. 3

• Baseline left ventricular ejection fraction (LVEF) assessment is mandatory before starting trastuzumab. 1, 3
• Patients with LVEF <55%, history of congestive heart failure, uncontrolled arrhythmias, or significant cardiac disease are not eligible. 4
• Permanently discontinue trastuzumab if congestive heart failure develops or persistent/recurrent LVEF decline occurs. 4

Critical pitfall to avoid:

• Never combine trastuzumab with anthracyclines concurrently—this causes 27% cardiac dysfunction rate versus 8% with sequential therapy. 2
• Trastuzumab should be initiated AFTER completing anthracycline cycles, concurrent only with taxane portion. 4

Special Populations and Alternative Regimens

For hormone receptor-positive, HER2-positive disease with low burden or contraindications to chemotherapy:

• Endocrine therapy plus trastuzumab or lapatinib may be considered in highly selected cases. 1
• However, the majority of patients should still receive chemotherapy plus HER2-targeted therapy. 1

For patients with cardiac contraindications:

• Consider the TCH regimen (docetaxel/carboplatin/trastuzumab) which avoids anthracyclines entirely. 4
• Shorter durations of trastuzumab (6 months) may serve as an alternative for patients with cardiac disease, though this provides inferior survival outcomes. 5

Radiation Therapy Coordination

All chemotherapy should be completed before starting radiation therapy. 2

• HER2-targeted therapy (trastuzumab/pertuzumab) can continue during radiation. 2
• Radiation is initiated after chemotherapy completion but while trastuzumab continues. 4