Recommended Chemotherapy Regimen for Triple-Negative Breast Cancer
For early-stage TNBC (stage II-III), the preferred regimen is neoadjuvant pembrolizumab combined with carboplatin plus paclitaxel, followed by pembrolizumab with cyclophosphamide plus doxorubicin or epirubicin, then continued adjuvant pembrolizumab regardless of pathologic response. 1
Early-Stage TNBC (Stage I-III)
Preferred Neoadjuvant Approach
High-risk TNBC (stage II-III) should receive:
- Preoperative pembrolizumab + carboplatin + paclitaxel, followed by preoperative pembrolizumab + cyclophosphamide + doxorubicin or epirubicin 1
- Continue adjuvant pembrolizumab after surgery regardless of pathologic response 2, 3
- This is a Category 1 recommendation and the benefit is independent of PD-L1 status 2
Alternative preferred regimens (all Category 1): 1
- Dose-dense AC (doxorubicin/cyclophosphamide) followed or preceded by paclitaxel every 2 weeks 1
- Dose-dense AC followed or preceded by weekly paclitaxel 1
- TC (docetaxel and cyclophosphamide) 1
Post-Neoadjuvant Adjuvant Therapy
For patients with residual disease after neoadjuvant chemotherapy:
- Add capecitabine for 6-8 cycles if germline BRCA1/2 wild-type (reduces death risk by 48%) 1, 2
- Add olaparib for 1 year if germline BRCA1/2 mutations present (Category 1) 1, 2
For patients achieving pathologic complete response:
- Continue pembrolizumab if it was part of neoadjuvant therapy 2, 3
- Consider olaparib for 1 year if germline BRCA1/2 mutations and ≥pT2 or ≥pN1 disease 1
Stage I TNBC
For lower-risk stage I disease:
- Anthracycline/taxane-based chemotherapy remains standard 1, 4
- Consider adding carboplatin and pembrolizumab for higher-risk features (young age, high-grade histology) 1, 3
- Very small tumors with low-risk histology may avoid chemotherapy 4
Metastatic TNBC
First-Line Treatment Algorithm
PD-L1-positive disease (≥1% tumor-infiltrating immune cells):
- Atezolizumab plus nab-paclitaxel (median OS 25 vs 15.5 months; HR 0.62) 2
- Alternative: Pembrolizumab plus chemotherapy 1, 5
- This is a strong recommendation with moderate evidence quality 1
PD-L1-negative disease:
- Single-agent chemotherapy is preferred over combination therapy 1, 5
- Weekly paclitaxel 80 mg/m² is superior to every-3-week dosing 2
- Combination chemotherapy reserved only for symptomatic visceral crisis or immediately life-threatening disease 1, 5
Germline BRCA1/2 mutations:
- Platinum agents (carboplatin or cisplatin) are preferred first-line options 2, 6
- Reserve PARP inhibitors for after progression on chemotherapy 6
Second-Line and Beyond
After ≥2 prior therapies:
- Sacituzumab govitecan is strongly recommended (ORR 35% vs 5%; median PFS 5.6 vs 1.7 months; HR 0.41) 1, 2, 3
Germline BRCA1/2 mutations after prior chemotherapy:
- PARP inhibitors (olaparib or talazoparib) are preferred over chemotherapy 1, 5, 3
- This is a strong recommendation with moderate evidence quality 1
Other second-line options:
- Anthracyclines if previously received taxanes, or vice versa 5
- Capecitabine, eribulin, gemcitabine, carboplatin/cisplatin, vinorelbine 5, 6
Critical Dosing and Administration Details
Paclitaxel dosing:
- Adjuvant setting: 175 mg/m² IV over 3 hours every 3 weeks for 4 courses 7
- Metastatic setting: 135-175 mg/m² IV over 3 hours every 3 weeks 7
- Weekly dosing: 80 mg/m² superior to every-3-week administration 1, 2
Premedication requirements:
- Dexamethasone 20 mg PO at 12 and 6 hours before paclitaxel 7
- Diphenhydramine 50 mg IV 30-60 minutes prior 7
- Cimetidine 300 mg or ranitidine 50 mg IV 30-60 minutes prior 7
Dose modifications:
- Hold treatment until neutrophils ≥1,500 cells/mm³ and platelets ≥100,000 cells/mm³ 7
- Reduce dose by 20% for severe neutropenia (<500 cells/mm³ for ≥1 week) or severe peripheral neuropathy 7
Essential Testing Requirements
All TNBC patients must undergo:
- Germline BRCA1/2 mutation testing to identify PARP inhibitor candidates 2, 3
- PD-L1 testing (≥1% tumor-infiltrating immune cells) to guide immunotherapy decisions 2
Common Pitfalls to Avoid
Do not use combination chemotherapy routinely in metastatic PD-L1-negative TNBC - single-agent therapy minimizes toxicity without compromising survival except in visceral crisis 1, 5
Do not withhold pembrolizumab based on PD-L1 status in early-stage disease - the benefit is independent of PD-L1 expression 2
Do not forget capecitabine after residual disease - this provides significant survival benefit in BRCA wild-type patients 1, 2
Do not use PARP inhibitors first-line in metastatic BRCA-mutated TNBC - platinum agents should be used first, reserving PARP inhibitors for later lines 6