What is the preferred initial treatment approach for patients with HER2 (human epidermal growth factor receptor 2) enriched breast cancer, upfront surgery or neoadjuvant chemotherapy?

Neoadjuvant Chemotherapy is Preferred Over Upfront Surgery for HER2-Positive Breast Cancer Stage II-III

For patients with clinical stage II-III HER2-positive breast cancer, neoadjuvant systemic chemotherapy with anti-HER2 therapy is the preferred initial treatment approach rather than upfront surgery. 1

Treatment Algorithm Based on Disease Stage

Stage II-III HER2+ Breast Cancer (T >2 cm or node positive)

• First choice: Neoadjuvant chemotherapy + dual HER2 blockade (trastuzumab + pertuzumab) 1
  • Chemotherapy backbone options:
    • Anthracycline-taxane sequence
    • Taxane-carboplatin (anthracycline-free) regimen 1
  • Complete planned chemotherapy before surgery
  • Follow with surgery, radiation if indicated, and completion of anti-HER2 therapy

Stage I (T1a-b N0) HER2+ Breast Cancer

• First choice: Primary surgery followed by adjuvant therapy 1
  • Adjuvant treatment: 12 weeks of paclitaxel plus 1 year of trastuzumab 1

Benefits of Neoadjuvant Approach for HER2+ Breast Cancer

1. Downstaging of tumor: Reduces extent of surgical intervention needed 1
2. Pathological response assessment: Allows evaluation of treatment efficacy in vivo 1
3. Risk stratification: Guides subsequent adjuvant therapy decisions 1
4. Improved breast conservation rates: Increases opportunity for breast-conserving surgery 1

Post-Neoadjuvant Treatment Based on Response

If Complete Pathologic Response (pCR)

• Continue trastuzumab + pertuzumab to complete 1 year (18 cycles) of treatment 1
• Add endocrine therapy if HR-positive 1

If Residual Disease (non-pCR)

• Switch to T-DM1 (trastuzumab emtansine) for up to 14 cycles 1
• This approach significantly improves invasive disease-free survival 1

Chemotherapy Regimen Selection

• Dual HER2 blockade: Trastuzumab + pertuzumab achieves higher pCR rates (50-70%) compared to trastuzumab alone 1
• Chemotherapy backbone options:
  • Anthracycline-taxane sequence (standard approach)
  • Taxane-carboplatin (anthracycline-free) regimen with similar efficacy but improved cardiac safety 1
  • Duration: 12-24 weeks (4-8 cycles) depending on regimen and disease stage 1

Important Considerations

• Cardiac monitoring: Regular cardiac assessments are required before, during, and after HER2-targeted therapy 1
• Hormone receptor status: Affects long-term therapy decisions (endocrine therapy added for HR+ disease) 1
• Duration of anti-HER2 therapy: Complete 12 months of HER2-directed therapy across neoadjuvant and adjuvant phases 1

Common Pitfalls to Avoid

1. Missing the opportunity for response-guided therapy: Starting with surgery eliminates the ability to use pathologic response to guide subsequent treatment decisions 1
2. Underestimating the prognostic value of pCR: Patients achieving pCR have substantially lower risk of recurrence 1
3. Inadequate HER2 testing: Ensure HER2 status is confirmed using FDA-approved tests by proficient laboratories 2
4. Overlooking cardiac toxicity risk: Regular cardiac monitoring is essential during HER2-targeted therapy 1, 2

The evidence strongly supports neoadjuvant therapy as the preferred approach for stage II-III HER2-positive breast cancer, with upfront surgery reserved primarily for early-stage (T1a-b N0) disease. This approach allows for response-guided therapy decisions and potentially improves long-term outcomes.