Treatment of Triple Negative Breast Cancer

Introduction to Treatment Regimens

The American Society of Clinical Oncology and the American College of Oncology recommend pembrolizumab 200 mg IV every 3 weeks, combined with sequential chemotherapy, for stage II or III TNBC, with benefits independent of PD-L1 status and germline BRCA1/2 status 1, 2
The preferred regimen for TNBC includes pembrolizumab 200 mg IV every 3 weeks, combined with sequential chemotherapy: initial 4 cycles of Paclitaxel + Carboplatin, followed by 4 cycles of Anthracycline (doxorubicin or epirubicin) + Cyclophosphamide, as per the KN522 trial protocol 2

Sequential use of anthracyclines and taxanes is superior to concomitant use and is much less toxic, according to the European Society for Medical Oncology, with a strength of evidence based on a 2019 study 3, 4
The National Comprehensive Cancer Network recommends dose-dense AC followed by paclitaxel, with doxorubicin 60 mg/m² IV, day 1, cyclophosphamide 600 mg/m² IV, day 1, cycled every 14 days for 4 cycles with filgrastim support, followed by paclitaxel 175 mg/m² by 3-h IV, day 1, every 14 days for 4 cycles 5
The National Comprehensive Cancer Network suggests TAC chemotherapy, with doxorubicin 50 mg/m² IV, day 1, docetaxel 75 mg/m² IV, day 1, cyclophosphamide 500 mg/m² IV, day 1, cycled every 21 days for 6 cycles with filgrastim support 5
The National Comprehensive Cancer Network recommends TC chemotherapy, with docetaxel 75 mg/m², cyclophosphamide 600 mg/m² IV, day 1, cycled every 21 days for 4 cycles 5
Taxane-based regimens are standard of care in first-line therapy for patients who received adjuvant anthracycline-based non-taxane-containing chemotherapy, according to the European Society for Medical Oncology 6

Older patients may require dose adjustments but should receive full doses whenever feasible, as suggested by the American Geriatrics Society and the European Society for Medical Oncology, with a strength of evidence not specified 1, 4
The capecitabine dosage of 1,250 mg/m² twice daily is associated with higher toxicity in patients ≥65 years old, with a strength of evidence based on a 2018 study 1
Hand-foot syndrome is the most frequent adverse event with capecitabine (73.4% of patients), with 11.1% experiencing grade 3 events, according to the National Cancer Institute, with a strength of evidence based on a 2018 study 1
Cardiac monitoring is essential when using anthracycline-containing regimens, as recommended by the National Comprehensive Cancer Network 5
Monitor for immune-related adverse events, particularly thyroid dysfunction 7

Definitive surgery is recommended after completion of neoadjuvant therapy, followed by pembrolizumab 200 mg IV every 3 weeks for up to 9 additional cycles, regardless of pathological complete response (pCR) status 2
For patients with residual disease after neoadjuvant therapy, continue pembrolizumab for nine courses (if given in neoadjuvant setting) and consider capecitabine every 3 weeks for six or eight cycles if gBRCA1/2-wildtype 2
Chemotherapy should be given before radiotherapy, except with CMF regimens, according to the National Comprehensive Cancer Network 5
The choice between regimens should be based on disease stage, patient factors, and treatment setting, with more intensive regimens for higher stage disease 5