Management of T3N1M0 Hormone Receptor-Negative, HER2-Positive Breast Cancer

Neoadjuvant Systemic Therapy

• The American College of Surgeons recommends neoadjuvant chemotherapy with trastuzumab, pertuzumab, and a taxane for 3-6 cycles, followed by surgery, radiation therapy, and completion of one year of adjuvant HER2-targeted therapy for patients with T3N1M0 hormone receptor-negative, HER2-positive breast cancer 1
• The standard neoadjuvant regimen should include trastuzumab, pertuzumab, and a taxane, with the taxane component being docetaxel 75-100 mg/m² every 3 weeks or weekly paclitaxel 80 mg/m² for 12 weeks 1

Surgical Management

• Definitive surgery, such as mastectomy or breast-conserving surgery with axillary lymph node dissection, should be performed after completing neoadjuvant chemotherapy for patients with T3N1M0 hormone receptor-negative, HER2-positive breast cancer 1

Radiation Therapy

• Postmastectomy radiation therapy is mandatory for T3N1 disease due to the locally advanced presentation and nodal involvement, and should be administered after completion of all chemotherapy but can be given concurrently with HER2-targeted therapy 2

Adjuvant Therapy

• The American Society of Clinical Oncology recommends continuing trastuzumab + pertuzumab to complete one year of HER2-targeted therapy for patients who achieve pathologic complete response after neoadjuvant therapy 1
• For patients with residual disease after neoadjuvant therapy, the National Comprehensive Cancer Network recommends switching to trastuzumab deruxtecan as adjuvant therapy, or continuing trastuzumab + pertuzumab if trastuzumab deruxtecan is unavailable 1

Treatment Duration and Monitoring

• HER2-targeted therapy should continue for a total of one year from the start of neoadjuvant treatment, and should not be discontinued after completing chemotherapy 1

Critical Pitfalls to Avoid

• Omitting pertuzumab from the initial regimen is not recommended, as the combination of trastuzumab + pertuzumab + taxane is the evidence-based standard with high-quality evidence 3, 4, 5, 1
• Stopping HER2-targeted therapy when chemotherapy is completed is not recommended, as HER2-targeted therapy must continue for the full year 3, 4, 1
• Omitting radiation therapy in T3N1 disease is not recommended, as postmastectomy radiation is mandatory for locoregional control 2