Neoadjuvant Chemotherapy for Triple Negative Breast Cancer
Recommended Regimen
For this 36-year-old female with 4.8 cm invasive triple negative breast cancer, the standard neoadjuvant approach is pembrolizumab combined with sequential anthracycline-taxane chemotherapy, followed by continued pembrolizumab as adjuvant therapy after surgery. 1, 2, 3
Specific Treatment Protocol
Neoadjuvant Phase (Pre-Surgery)
Cycles 1-4 (12 weeks):
- Pembrolizumab 200 mg IV every 3 weeks on Day 1 3
- PLUS Carboplatin AUC 5 mg/mL/min IV every 3 weeks on Day 1 (or AUC 1.5 mg/mL/min weekly on Days 1,8,15) 3
- PLUS Paclitaxel 80 mg/m² IV weekly on Days 1,8, and 15 3
Cycles 5-8 (12 weeks):
- Pembrolizumab 200 mg IV every 3 weeks on Day 1 3
- PLUS Doxorubicin 60 mg/m² IV every 3 weeks on Day 1 (or Epirubicin 90 mg/m²) 3
- PLUS Cyclophosphamide 600 mg/m² IV every 3 weeks on Day 1 3
Surgical Phase
- Definitive surgery after completion of 8 cycles of neoadjuvant therapy 3
Adjuvant Phase (Post-Surgery)
- Pembrolizumab 200 mg IV every 3 weeks for 9 additional cycles 3
Evidence Supporting This Approach
The KEYNOTE-522 trial demonstrated that adding pembrolizumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates in high-risk early-stage TNBC (defined as tumors >2 cm regardless of nodal status, which applies to this 4.8 cm tumor) 3. This regimen is FDA-approved and represents the current standard of care 3.
The sequential anthracycline-taxane approach is evidence-based for TNBC, with dose-dense regimens preferred when feasible 1. The addition of carboplatin provides benefit independent of BRCA mutation status 1.
Alternative Regimens (If Pembrolizumab Unavailable)
If pembrolizumab cannot be administered, acceptable alternatives include:
- Dose-dense AC followed by paclitaxel: Doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² every 14 days × 4 cycles with G-CSF support, followed by paclitaxel 175 mg/m² every 14 days × 4 cycles 1
- TAC regimen: Docetaxel 75 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m² every 21 days × 6 cycles with filgrastim support 1
Critical Considerations
Pathological complete response (pCR) is a critical prognostic indicator in TNBC 1, 3. If residual invasive disease is present after neoadjuvant therapy, adjuvant capecitabine (6-8 cycles) should be considered to reduce recurrence risk 1.
Platinum agents (carboplatin) should be included in the neoadjuvant regimen for TNBC, as they improve pCR rates regardless of BRCA mutation status 1. The benefit of platinum is particularly relevant in this young patient with a large tumor.
All chemotherapy should be delivered preoperatively when using a neoadjuvant approach, rather than splitting between pre- and post-operative periods 1.
Monitoring Requirements
- Cardiac function monitoring is mandatory before and during anthracycline administration 1
- Immune-related adverse events must be monitored closely during pembrolizumab therapy, as they can affect any organ system 2
- Tumor assessment should be performed after completion of neoadjuvant therapy to determine surgical approach and assess for pCR 3
Common Pitfalls to Avoid
Do not omit pembrolizumab in eligible patients - the KEYNOTE-522 trial showed significant improvements in both pCR and event-free survival with the addition of pembrolizumab to chemotherapy 3. This represents a major advance in TNBC treatment.
Do not use single-agent chemotherapy in the neoadjuvant setting for this tumor size - combination regimens are required for tumors >2 cm to maximize the chance of pCR and breast conservation 1, 2.
Do not delay surgery beyond completion of planned neoadjuvant cycles unless there is documented progression requiring alternative therapy 1.
Ensure G-CSF support is provided with dose-dense regimens to maintain treatment intensity and prevent dose delays 1.