What is the recommended neoadjuvant chemotherapy regimen for early breast cancer?

Neoadjuvant Chemotherapy Regimens for Early Breast Cancer

For early breast cancer, the recommended neoadjuvant chemotherapy regimen should be tailored based on tumor subtype, with anthracycline-taxane combinations for triple-negative and HER2-positive disease, and consideration of endocrine therapy for select hormone receptor-positive cases. 1

General Principles of Neoadjuvant Therapy

• Neoadjuvant therapy is preferred for stage II-III breast cancer, particularly for HER2-positive and triple-negative subtypes, as it provides effective systemic therapy, improves surgical options, and allows for tailoring of adjuvant treatment based on response 1
• Neoadjuvant chemotherapy increases rates of breast-conserving surgery in early operable breast cancer without compromising overall survival compared to adjuvant chemotherapy 2, 3
• The same chemotherapy regimens used in the adjuvant setting are recommended for neoadjuvant treatment 1

Subtype-Specific Recommendations

HER2-Positive Breast Cancer

• For stage II-III HER2-positive breast cancer, neoadjuvant chemotherapy with dual HER2 blockade (trastuzumab and pertuzumab) is strongly recommended 1
• Chemotherapy backbone options include:
  • Anthracycline-taxane sequential regimens 1
  • Taxane-carboplatin combinations (anthracycline-free) which show similar outcomes with improved cardiac safety 1
• Dual HER2 blockade with trastuzumab-pertuzumab achieves higher pathologic complete response (pCR) rates than trastuzumab alone 1
• Post-neoadjuvant treatment should be based on response:
  • For patients achieving pCR: continue anti-HER2 therapy to complete 1 year of treatment 1
  • For patients with residual disease: switch to T-DM1 (trastuzumab emtansine) for 14 cycles 1

Triple-Negative Breast Cancer (TNBC)

• Neoadjuvant therapy is the standard approach for stage II-III TNBC 1
• Preferred regimen includes:
  • Sequential therapy with either anthracycline-based regimens followed by taxanes, or taxanes with carboplatin followed by anthracycline-based therapy 1
  • Addition of pembrolizumab to chemotherapy is recommended based on the KN522 trial 1
  • Standard anthracycline regimens include doxorubicin-cyclophosphamide (AC) or epirubicin-cyclophosphamide (EC) for four cycles followed by a taxane 1
  • The benefit of carboplatin is independent of germline BRCA1/2 status 1

Hormone Receptor (HR)-Positive/HER2-Negative Breast Cancer

• Neoadjuvant chemotherapy can effectively downstage HR-positive/HER2-negative cancers for surgical purposes, although pCR is less common 1
• For patients with low-risk genomic signatures or those who are not candidates for chemotherapy, neoadjuvant endocrine therapy for at least 6 months is an option 1
• Appropriate candidates for neoadjuvant endocrine therapy are patients with estrogen receptor-rich tumors (Allred 7-8) 1
• Anthracycline-taxane based regimens are recommended for patients requiring chemotherapy 1

Specific Chemotherapy Regimens

• Anthracycline-taxane sequential regimens:
  • Doxorubicin-cyclophosphamide (AC) × 4 followed by taxane × 4 1
  • Epirubicin-cyclophosphamide (EC) × 4 followed by taxane × 4 1
  • Fluorouracil-epirubicin-cyclophosphamide × 3 followed by docetaxel × 3 1
• Non-anthracycline regimens:
  • Docetaxel-cyclophosphamide × 4 (alternative with improved DFS and OS) 1
  • Taxane-carboplatin combinations (especially for HER2-positive disease) 1

Post-Neoadjuvant Treatment Considerations

• Response to neoadjuvant therapy provides important prognostic information and guides adjuvant treatment 4
• For HER2-positive disease with residual tumor, switch to T-DM1 for 14 cycles 1
• For TNBC with residual disease after standard neoadjuvant chemotherapy, consider adjuvant capecitabine 1
• For HR-positive disease, adjuvant endocrine therapy is recommended based on menopausal status 1

Common Pitfalls and Caveats

• Tumors downsized by neoadjuvant chemotherapy may have higher local recurrence rates after breast-conserving therapy compared to tumors of the same dimensions without prior neoadjuvant treatment 3
• Regular cardiac monitoring is mandatory before and during trastuzumab treatment due to potential cardiotoxicity 1, 5
• Dose modifications may be necessary for patients with hepatic impairment to prevent excessive toxicity 6
• For patients receiving anthracyclines, cumulative dose limits should be observed (doxorubicin ≤240 mg/m² or epirubicin ≤720 mg/m²) 1

Neoadjuvant chemotherapy has evolved to become an important treatment approach for early breast cancer, offering the advantages of tumor downstaging, increased breast conservation rates, and the opportunity to assess in vivo tumor response to guide subsequent therapy 4, 7, 8.