What is the recommended management for a patient with T3N1M0 hormone negative HER2 (Human Epidermal growth factor Receptor 2) positive breast cancer?

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

For T3N1M0 hormone receptor-negative, HER2-positive breast cancer, neoadjuvant chemotherapy with trastuzumab, pertuzumab, and a taxane should be administered for 3-6 cycles, followed by surgery, radiation therapy, and completion of one year of adjuvant HER2-targeted therapy. 1, 2

Neoadjuvant Systemic Therapy (Preferred Approach)

Neoadjuvant therapy is the preferred treatment sequence for locally advanced HER2-positive breast cancer, even when operable, as it allows for assessment of treatment response and guides subsequent therapy decisions. 2

Standard Neoadjuvant Regimen

• Administer trastuzumab (initial dose 8 mg/kg, then 6 mg/kg every 3 weeks) + pertuzumab (initial dose 840 mg, then 420 mg every 3 weeks) + taxane (docetaxel or paclitaxel) for 3-6 cycles preoperatively. 1, 3
• The taxane component should be docetaxel 75-100 mg/m² every 3 weeks or weekly paclitaxel 80 mg/m² for 12 weeks. 1
• Cardiac function must be evaluated before initiating therapy and monitored during treatment, as both trastuzumab and pertuzumab can cause left ventricular dysfunction. 3

Surgical Management

• Perform definitive surgery (mastectomy or breast-conserving surgery with axillary lymph node dissection) after completing neoadjuvant chemotherapy. 1
• Pathologic assessment of residual disease at surgery is critical for determining subsequent adjuvant therapy. 2

Radiation Therapy

• Postmastectomy radiation therapy is mandatory for T3N1 disease due to the locally advanced presentation and nodal involvement. 4
• Radiation should be administered after completion of all chemotherapy but can be given concurrently with HER2-targeted therapy. 4

Adjuvant Therapy Based on Pathologic Response

If Pathologic Complete Response (pCR) Achieved

• Continue trastuzumab + pertuzumab to complete one year (up to 18 cycles total) of HER2-targeted therapy. 1

If Residual Disease Present After Neoadjuvant Therapy

• Switch to trastuzumab deruxtecan (T-DXd) as adjuvant therapy based on the most recent evidence showing superior outcomes in patients with residual disease. 1
• If T-DXd is unavailable, continue trastuzumab + pertuzumab to complete one year of therapy. 1

Treatment Duration and Monitoring

• HER2-targeted therapy should continue for a total of one year (up to 18 cycles) from the start of neoadjuvant treatment. 1
• Do not discontinue HER2-targeted therapy after completing chemotherapy—continue until one year of total HER2-targeted therapy is achieved or until unacceptable toxicity occurs. 1
• Monitor left ventricular ejection fraction every 3 months during HER2-targeted therapy. 3

Critical Pitfalls to Avoid

• Do not use adjuvant chemotherapy first followed by surgery in locally advanced HER2-positive disease—neoadjuvant therapy is superior as it allows response-guided treatment decisions. 2
• Do not omit pertuzumab from the initial regimen—the combination of trastuzumab + pertuzumab + taxane is the evidence-based standard with high-quality evidence. 5, 1
• Do not stop HER2-targeted therapy when chemotherapy is completed—HER2-targeted therapy must continue for the full year. 5, 1
• Do not omit radiation therapy in T3N1 disease—postmastectomy radiation is mandatory for locoregional control. 4