Triple-negative breast cancer (TNBC): lines of therapy

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5 standard-of-care settings across 3 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	PD-L1
Early / localised	2	·
Advanced, first line	·	2
Third line and beyond	1	·

Early / localised

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Stage I (T1a-b N0)	Surgery ± radiation; chemotherapy for ≥T1c; TIL-high tumours have >90% 5-year RFS even without chemotherapy (OPTimal, ETNA, TIL-CHOICE cohorts). De-escalation trials ongoing.	Sentinel lymph node biopsyHistopathology & immunohistochemistry	NCCN Guidelines: Breast Cancer	68
All comers	Stage II-III	Neoadjuvant pembrolizumab + carboplatin/paclitaxel → AC/EC, surgery, adjuvant pembrolizumab (KEYNOTE-522). Germline BRCA + residual disease: olaparib 1 year (OlympiA). Residual disease without BRCA: capecitabine (CREATE-X). Radiation per stage.	KEYNOTE-522PembrolizumabCarboplatinOlaparibOlympiA	NCCN · Category 1, preferred: neoadjuvant pembroli…ESMO-MCBS · A (KEYNOTE-522); A (OlympiA)	98

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
PD-L1	Metastatic, first line, PD-L1 CPS ≥10	Pembrolizumab + chemotherapy (KEYNOTE-355) or sacituzumab govitecan + pembrolizumab (ASCENT-04, approved 2026).	KEYNOTE-355ASCENT-04 / KEYNOTE-D19Sacituzumab govitecanPembrolizumab	NCCN · Category 1, preferred: sacituzumab goviteca…ESMO-MCBS · 4 (KEYNOTE-355)	98
PD-L1	Metastatic, first line, PD-L1 negative or PD-1 ineligible	Datopotamab deruxtecan (TROPION-Breast02, OS benefit) or sacituzumab govitecan (ASCENT-03), both approved 2026; PARP inhibitor if germline BRCA; chemotherapy.	TROPION-Breast02ASCENT-03Datopotamab deruxtecanOlaparib	NCCN · Category 1, preferred: sacituzumab goviteca…	88

Third line and beyond

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Metastatic, later lines	Whichever TROP2 ADC was not used first (cross-resistance uncertain); T-DXd if HER2-low (DESTINY-Breast04); iza-bren where available; chemotherapy (eribulin, capecitabine); clinical trials.	Trastuzumab deruxtecanIzalontamab brengitecanDESTINY-Breast04	ESMO-MCBS · 4 (ASCENT; re-scored 5 in the breast-cancer…	97

Sequence and caution pairings

CautionApproved

Caution: cumulative anthracycline dose and the heart

Every dose of doxorubicin adds to a lifetime total; above roughly 450 mg/m2 heart failure risk rises steeply, so sarcoma and lymphoma regimens are capped and hearts are monitored.

CautionApproved

Caution: DXd ADC + agents with pneumonitis risk

Enhertu and its DXd cousins can inflame the lungs; combining them with immunotherapy, radiation, or mTOR inhibitors stacks that risk.

CautionApproved

Caution: TOP1 ADC immediately after TOP1 ADC

Giving a second ADC with the same kind of payload straight after the first often does not work well.

Regimens in the library

Dose-dense AC → T TC (docetaxel + cyclophosphamide)KEYNOTE-522 (pembrolizumab + chemotherapy, then adjuvant pembrolizumab)Trastuzumab deruxtecan 5.4 mg/kg Sacituzumab govitecan Capecitabine (post-neoadjuvant)Olaparib (adjuvant, OlympiA)Eribulin Weekly paclitaxel

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.