What is the recommended treatment for triple negative breast cancer according to National Comprehensive Cancer Network (NCCN) guidelines?

NCCN Treatment Recommendations for Triple-Negative Breast Cancer

For early-stage triple-negative breast cancer, the NCCN recommends neoadjuvant chemotherapy with pembrolizumab plus taxane-carboplatin-anthracycline-cyclophosphamide regimens for stage II-III disease, followed by adjuvant pembrolizumab regardless of pathologic response, with adjuvant capecitabine or olaparib added based on residual disease and BRCA mutation status. 1

Early-Stage Disease (Stage I-III)

Neoadjuvant Therapy - Preferred Approach

For stage II-III TNBC, the preferred regimen is pembrolizumab combined with sequential chemotherapy: 1

• Pembrolizumab with nab-paclitaxel followed by anthracycline-cyclophosphamide is the category 1 recommendation 1
• The pembrolizumab benefit is independent of PD-L1 status 2
• After completing neoadjuvant pembrolizumab plus chemotherapy, continue adjuvant pembrolizumab regardless of pathologic response 1

Alternative Neoadjuvant Regimens

For patients where pembrolizumab is not appropriate: 1

• Dose-dense AC followed by weekly paclitaxel (every 2 weeks with growth factor support) 1
• Docetaxel-cyclophosphamide (TC) for patients with anthracycline contraindications 1
• Weekly paclitaxel is superior to every-3-week paclitaxel (HR 1.27 for DFS, p=0.006) 1

Post-Neoadjuvant Adjuvant Therapy

The treatment after neoadjuvant therapy depends on pathologic response and BRCA status: 1

For patients with residual disease after neoadjuvant chemotherapy:

• Adjuvant capecitabine for 6-8 cycles if germline BRCA1/2 wild-type (HR for death 0.52 in TNBC) 1, 2
• Adjuvant olaparib for 1 year if germline BRCA1/2 mutations present and residual disease after preoperative chemotherapy (category 1) 1

For patients achieving pathologic complete response:

• If germline BRCA1/2 mutations: consider olaparib for 1 year if ≥pT2 or ≥pN1 disease before neoadjuvant therapy 1

Adjuvant Therapy (Primary Surgery Approach)

For patients treated with upfront surgery: 1

Preferred regimens include:

• Dose-dense AC followed by weekly or biweekly paclitaxel 1
• Docetaxel-cyclophosphamide (TC) 1

Risk-based treatment thresholds: 1

• Tumors ≤0.5 cm: no adjuvant therapy 1
• Tumors 0.6-1.0 cm: consider adjuvant chemotherapy 1
• Tumors >1 cm or node-positive: adjuvant chemotherapy (category 1) 1

Metastatic/Recurrent Disease

First-Line Therapy

Treatment selection depends on PD-L1 status and BRCA mutation status: 1, 3

For PD-L1-positive metastatic TNBC (≥1% tumor-infiltrating immune cells):

• Atezolizumab plus nab-paclitaxel is the preferred regimen (median OS 25 vs 15.5 months; HR 0.62) 1, 3
• This combination improved PFS (7.5 vs 5 months; HR 0.62) and OS significantly 1

For PD-L1-negative or when immunotherapy not appropriate: 1, 3

Preferred single-agent chemotherapy options:

• Weekly paclitaxel (80 mg/m²) - superior to every-3-week dosing 1, 3
• Nab-paclitaxel (125 mg/m² weekly, not to exceed this dose when substituting for paclitaxel) 1
• Doxorubicin (60-75 mg/m² every 3 weeks or 20 mg/m² weekly; ORR 30-47%) 1
• Liposomal doxorubicin (50 mg/m² every 4 weeks) - less cardiotoxicity than doxorubicin (7% vs 26%) 1
• Capecitabine (ORR 28%, median OS 15.2 months) 1
• Eribulin 1

For germline BRCA1/2 mutations:

• Platinum agents (carboplatin or cisplatin) are preferred options 1, 3
• In the TNT trial, carboplatin showed superior ORR in BRCA-mutated patients (68% vs 33.3% with docetaxel, p=0.03) 1

Preferred combination regimens (for symptomatic visceral crisis or rapidly progressive disease): 1, 3

• Nab-paclitaxel plus carboplatin - superior to other combinations (median PFS 8.3 months, ORR 73%) 1
• Gemcitabine/carboplatin (median OS 11.1 months) 1

Second-Line and Beyond

For patients with germline BRCA1/2 mutations who received prior chemotherapy: 1, 3, 2

• Olaparib or talazoparib (PARP inhibitors) are category 1 preferred over chemotherapy 1
• Olaparib: median PFS 7.0 months vs 4.2 months with chemotherapy 2
• Talazoparib: median PFS 8.6 months vs 5.6 months (HR 0.54, p<0.001) 1

For patients who received ≥2 prior therapies for metastatic disease:

• Sacituzumab govitecan is strongly recommended (ORR 35% vs 5%; median PFS 5.6 vs 1.7 months; HR 0.41) 3, 2

Other recommended second-line options: 1, 3

• Taxanes (if not previously used) 3
• Anthracyclines (if not previously used) 3
• Capecitabine 1
• Gemcitabine 1
• Eribulin 1

Important Treatment Principles

Sequential single-agent therapy is preferred over combination chemotherapy to minimize toxicity, except for: 3

• Symptomatic visceral crisis requiring rapid response 3
• Immediately life-threatening disease 3
• Rapidly progressive disease with risk of deterioration 3

Bevacizumab considerations: 1

• Bevacizumab plus weekly paclitaxel showed modest PFS improvement (7.4 months in TNBC subset) 1
• No OS or quality of life benefit demonstrated in meta-analyses 1
• Listed as "useful in only select circumstances" 1

Critical Toxicity Management

Platinum-based regimens cause significant hematologic toxicity: 4

• Grade III/IV neutropenia increased 53% (RR 1.53) 4
• Grade III/IV anemia increased 8-fold (RR 8.20) 4
• Grade III/IV thrombocytopenia increased 7.6-fold (RR 7.59) 4
• More frequent chemotherapy delays (RR 2.23) and dose reductions (RR 1.77) 4
• However, febrile neutropenia rates were similar (RR 1.16, not significant) 4
• Treatment-related death remained very rare (0.2%, similar across groups) 4

For pembrolizumab plus carboplatin regimens: 5

• Hold both agents if platelets <100,000/mm³ 5
• Recheck counts in 3-7 days 5
• Resume both agents together when platelets ≥100,000/mm³ and ANC ≥1,000/mm³ 5
• Consider G-CSF support for subsequent cycles 5

Essential Testing

All patients with TNBC should undergo: 1, 2

• Germline BRCA1/2 mutation testing to identify candidates for PARP inhibitors 1
• PD-L1 testing (≥1% tumor-infiltrating immune cells) to guide immunotherapy decisions 1