NCCN Guidelines for Triple-Negative Breast Cancer

Early-Stage Disease (Stage I-III)

The National Comprehensive Cancer Network 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, 2
Pembrolizumab with nab-paclitaxel followed by anthracycline-cyclophosphamide is the category 1 recommendation for stage II-III TNBC 1
The pembrolizumab benefit is independent of PD-L1 status 3
After completing neoadjuvant pembrolizumab plus chemotherapy, continue adjuvant pembrolizumab regardless of pathologic response 1, 2
For patients with residual disease after neoadjuvant chemotherapy, adjuvant capecitabine for 6-8 cycles is recommended if germline BRCA1/2 wild-type (HR for death 0.52 in TNBC) 1, 3
For patients with residual disease after neoadjuvant chemotherapy and germline BRCA1/2 mutations, adjuvant olaparib for 1 year is recommended (category 1) 1, 2

For PD-L1-positive metastatic TNBC, atezolizumab plus nab-paclitaxel is the preferred regimen (median OS 25 vs 15.5 months; HR 0.62) 4, 5
For PD-L1-negative or when immunotherapy is not appropriate, weekly paclitaxel (80 mg/m²) is a preferred single-agent chemotherapy option, superior to every-3-week dosing 6, 5
For germline BRCA1/2 mutations, platinum agents (carboplatin or cisplatin) are preferred options 4, 5
Olaparib or talazoparib (PARP inhibitors) are category 1 preferred over chemotherapy for patients with germline BRCA1/2 mutations who received prior chemotherapy 4
Sacituzumab govitecan is strongly recommended for patients who received ≥2 prior therapies for metastatic disease (ORR 35% vs 5%; median PFS 5.6 vs 1.7 months; HR 0.41) 5, 3

All patients with TNBC should undergo germline BRCA1/2 mutation testing to identify candidates for PARP inhibitors 4
PD-L1 testing (≥1% tumor-infiltrating immune cells) should be performed to guide immunotherapy decisions 4

The OlympiA trial demonstrated a 4-year overall survival (OS) of 89.8% with olaparib versus 86.4% with placebo in patients with germline BRCA1/2 mutation and residual disease after neoadjuvant chemotherapy, leading to a category 1 recommendation for adjuvant olaparib in this population 7

The NCCN provides traditional chemotherapy options, including dose-dense AC (doxorubicin/cyclophosphamide) followed by paclitaxel every 2 weeks, dose-dense AC followed by weekly paclitaxel, and TC (docetaxel and cyclophosphamide), as preferred regimens for patients who cannot receive immunotherapy 8
Other acceptable regimens include FAC/CAF, FEC/CEF, CMF, TAC, and various anthracycline-taxane combinations, according to the NCCN guidelines 8

The NCCN recommends that all chemotherapy regimens should be completed before initiating radiotherapy, to ensure proper sequencing of treatments 8

The American Society of Clinical Oncology recommends that patients with stage 3C triple-negative breast cancer who did not receive neoadjuvant chemotherapy should undergo adjuvant treatment, with the starting dose of capecitabine being 1,250 mg/m² orally twice daily, though this may require reduction in patients ≥65 years due to excessive toxicity 9

The National Comprehensive Cancer Network recommends that stage 3C disease carries sufficient risk for local recurrence to warrant chest wall and supraclavicular node irradiation, and if internal mammary lymph nodes are involved, they should also be irradiated 10

The American Society of Clinical Oncology notes that for patients with BRCA mutations, platinum agents (carboplatin or cisplatin) may be incorporated into the initial chemotherapy regimen given their superior response rates (68.0% vs 33.3% for docetaxel) 11, 12
Close monitoring is required for capecitabine-associated toxicities, including hand-foot syndrome and diarrhea, which can be life-threatening 9