For a patient with HER2-positive (Human Epidermal growth factor Receptor 2-positive) breast cancer who has achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) and surgery, should T-DM1 (trastuzumab emtansine) or trastuzumab (Herceptin) plus pertuzumab (Perjeta) be chosen as adjuvant therapy?

Post-Neoadjuvant Therapy for HER2+ Breast Cancer with pCR

If you achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy and surgery, continue trastuzumab plus pertuzumab (not T-DM1) to complete 1 year total of HER2-directed therapy. 1, 2

The Critical Distinction: pCR vs Residual Disease

The choice between T-DM1 and trastuzumab-pertuzumab depends entirely on whether residual invasive disease is present at surgery:

For Patients with pCR (Your Scenario)

• Continue pertuzumab plus trastuzumab to complete 18 cycles (1 year total) including the neoadjuvant period. 1, 2
• This is the standard recommendation from ESMO 2024 guidelines for patients who achieve pCR after neoadjuvant dual HER2 blockade. 1
• Patients with pCR demonstrate substantially lower risk of disease recurrence and do not require treatment escalation. 1

For Patients with Residual Disease (Not Your Scenario)

• Switch to T-DM1 for 14 cycles if any residual invasive disease is present in breast or lymph nodes. 1, 3, 2
• The KATHERINE trial established this as standard of care, showing T-DM1 reduces recurrence risk by 50% compared to continuing trastuzumab (HR 0.50,95% CI 0.39-0.64, p<0.001). 1, 3
• This benefit applies regardless of extent of residual disease, including node-negative disease with tumors <1 cm. 1

Why T-DM1 is NOT Indicated for pCR

T-DM1 is exclusively indicated for patients with residual invasive disease after neoadjuvant therapy—never for those who achieve pCR. 3, 2

The evidence is clear:

• T-DM1 was studied in KATHERINE trial specifically for residual disease patients. 1, 3
• Patients with pCR already have excellent prognosis and continuing the effective dual blockade regimen is appropriate. 1, 2
• Using T-DM1 in pCR patients would expose them to unnecessary toxicity (thrombocytopenia, elevated liver enzymes, higher discontinuation rates of 18% vs 2.1%) without evidence of benefit. 1, 3

Important Caveats About Risk Stratification

Even with pCR, baseline tumor burden matters:

• Patients with high initial tumor burden (≥2 cm and/or node-positive at diagnosis) remain at elevated risk of relapse even with pCR. 1
• This is why completing the full year of dual HER2 blockade is critical, particularly for node-positive disease at presentation. 1, 2
• The APHINITY trial showed that node-positive patients derived clear benefit from pertuzumab continuation (8-year iDFS 86% vs 81%, HR 0.72). 1

Practical Implementation

Complete 12 months total of trastuzumab-based therapy (18 cycles total including neoadjuvant period). 1, 2

• If you received dual blockade (pertuzumab-trastuzumab) neoadjuvantly and were node-positive at diagnosis, continue both agents. 1, 2
• Cardiac monitoring with LVEF assessment is mandatory before, during, and after HER2-targeted therapy. 3, 2
• If hormone receptor-positive, continue endocrine therapy for 5-10 years total. 3

Common Pitfall to Avoid

Do not switch to T-DM1 in patients with pCR—this represents misapplication of the KATHERINE trial results and exposes patients to unnecessary toxicity without benefit. 1, 3 The KATHERINE trial specifically excluded patients with pCR, and T-DM1 has never been studied or indicated for this population. 1