Recommended Chemotherapy for Triple-Negative Breast Cancer
For early-stage triple-negative breast cancer, anthracycline-taxane sequential regimens are the standard of care, with 4 cycles of doxorubicin/cyclophosphamide (AC) or epirubicin/cyclophosphamide (EC) followed by taxane therapy being the most strongly recommended approach. 1
Early-Stage/Adjuvant Setting
Standard Chemotherapy Backbone
Chemotherapy is recommended in the vast majority of triple-negative breast cancers 1, with the absolute benefit being more pronounced in ER-negative tumors 1
The preferred regimen consists of anthracyclines followed sequentially by taxanes 1, as sequential use is superior to concomitant administration and significantly less toxic 1
Standard anthracycline-based regimens are AC (doxorubicin/cyclophosphamide) or EC (epirubicin/cyclophosphamide) 1, with 5-fluorouracil dropped from these combinations as it adds no efficacy but increases toxicity 1
Four cycles of AC or EC are considered standard 1, followed by taxane therapy (paclitaxel or docetaxel) 1
Sequential vs. Combination Approach
Sequential anthracycline-taxane regimens reduce breast cancer mortality by approximately one-third 1, with the addition of taxanes improving efficacy independently of nodal status, tumor size, or grade 1
Both anthracycline-to-taxane and taxane-to-anthracycline sequences are acceptable 1, though some data suggest taxane-first may be slightly more effective 1
There is no place for routine use of 6-cycle three-drug anthracycline-based regimens 1, except possibly in patients with strong contraindications to taxanes 1
Metastatic Setting
First-Line Therapy
For PD-L1-positive metastatic TNBC, immune checkpoint inhibitor plus chemotherapy is recommended as first-line therapy 2, demonstrating improved progression-free survival compared to chemotherapy alone 2
For PD-L1-negative disease, single-agent chemotherapy is preferred 2, with combination chemotherapy reserved only for symptomatic or immediately life-threatening disease 2
Taxanes (paclitaxel or docetaxel) are preferred first-line options if not previously used in the adjuvant setting 2, representing the only standard of care with level 1 evidence for patients progressing after adjuvant anthracycline-based chemotherapy 3
Anthracyclines (doxorubicin or epirubicin) are recommended if not previously used 2
Platinum agents (carboplatin or cisplatin) with or without taxanes are appropriate options 2, showing particular efficacy in TNBC with potential small survival benefits but increased toxicity including nausea, vomiting, and anemia 2
Subsequent Lines of Therapy
For patients with germline BRCA1/2 mutations, PARP inhibitors (olaparib or talazoparib) are recommended rather than chemotherapy 2
Sacituzumab govitecan is strongly recommended for patients who have received at least two prior therapies for metastatic disease 2, with significant improvement in both progression-free survival and overall survival 2
Sequential single-agent chemotherapy is generally preferred over combination regimens to minimize toxicity 2, except in cases of visceral crisis or rapidly progressing disease 2
Critical Treatment Considerations
When to Use Combination vs. Sequential Therapy
Combination chemotherapy should only be used for symptomatic visceral crisis requiring rapid response, immediately life-threatening disease, or rapidly progressive disease with risk of patient deterioration 3
Triple-negative biology alone does not mandate combination chemotherapy 3
Sequential use of single cytotoxic drugs provides equivalent overall survival compared to combination chemotherapy, with less toxicity and better quality of life 3
Special Populations and Exceptions
Possible exception to chemotherapy exists for selected cases with very low risk T1abN0 disease 1
Special histological subtypes (adenoid cystic or apocrine) with N0 disease and no other risk factors may be observed without chemotherapy 1
Common Pitfalls to Avoid
Do not use 5-fluorouracil in anthracycline-based regimens 1, as it increases toxicity without adding efficacy 1
Avoid concomitant anthracycline-taxane administration 1, as sequential use is both more effective and less toxic 1
Do not routinely use combination chemotherapy in the metastatic setting 2, as it offers higher response rates but with increased toxicity and no overall survival benefit in most patients 2