Loading
10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that.
TNBC is defined by what it lacks: ER <1%, PR <1%, HER2 0-1+ (or 2+/ISH-negative). It is biologically heterogeneous (basal-like 1 and 2, mesenchymal, luminal androgen receptor, immunomodulatory subtypes), nearly always TP53-mutant, frequently HRD-positive (11 to 17% germline BRCA1/2 by cohort), and has the highest TROP2 expression and the most immune infiltration of any breast subtype. Relapses cluster in the first three years and favour visceral and brain metastases.
The standard of care changed three times in six years. KEYNOTE-522 (2020-21) made pembrolizumab plus carboplatin-containing chemotherapy before surgery, continued after, the standard for stage II-III disease, with a 4.9-point overall survival gain at five years (86.6% against 81.7%). OlympiA (2021) added adjuvant olaparib for germline BRCA carriers with residual disease. In metastatic disease, pembrolizumab-chemotherapy (CPS ≥10) was joined by the TROP2 ADCs: sacituzumab govitecan (ASCENT, second line 2020; first-line ASCENT-03/04 2026) and datopotamab deruxtecan (TROPION-Breast02, first-line PD-1-ineligible, 2026, with an overall survival benefit), while T-DXd covers the roughly one third of TNBC that is HER2-low (24 to 37% by cohort). The EGFR×HER3 bispecific ADC iza-bren posted the first positive phase 3 for a bispecific ADC in pretreated TNBC in February 2026.
| Setting | Approach | Guideline |
|---|---|---|
| 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. | not mapped |
| 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. | NCCN Category 1, preferred: neoadjuvant pembrolizumab + chemotherapy (KEYNOTE-522); adjuvant olaparib for gBRCA Category 2A, preferred, ESMO-MCBS A (KEYNOTE-522); A (OlympiA) |
| Metastatic, first line, PD-L1 CPS ≥10 | Pembrolizumab + chemotherapy (KEYNOTE-355) or sacituzumab govitecan + pembrolizumab (ASCENT-04, approved 2026). | NCCN Category 1, preferred: sacituzumab govitecan + pembrolizumab (NCCN Breast, February 2026); pembrolizumab + chemotherapy Category 1, ESMO-MCBS 4 (KEYNOTE-355) |
| 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. | NCCN Category 1, preferred: sacituzumab govitecan monotherapy (NCCN Breast, 2026) |
| 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. | ESMO-MCBS 4 (ASCENT; re-scored 5 in the breast-cancer analysis); 4 (DESTINY-Breast04) |
| Suspected cancer in primary care | Suspected cancer pathway referral for an unexplained breast lump at 30 or over, or discharge, retraction or other change in one nipple at 50 or over; consider it for skin changes or an unexplained axillary lump at 30 or over; non-urgent referral for a lump under 30 (NICE NG12 1.4). The clinic does triple assessment: examination, mammogram, ultrasound and core biopsy. | not mapped |
| Receptor testing that defines the subtype | ER, PR and HER2 assessed together on the diagnostic biopsy by quality-assured immunohistochemistry and reported quantitatively (NG101 1.3.1 to 1.3.4): ER and PR negative under 1 percent, ER 1 to 10 percent reported as low positive, HER2 0 or 1+ or 2+ without amplification. HER2 0 versus 1+ is reported with a comment because HER2-low disease qualifies for trastuzumab deruxtecan. | not mapped |
| Germline testing at diagnosis | Germline BRCA1 and BRCA2 testing for women under 50 with triple-negative breast cancer including those with no family history (NG101 1.3.6); UK mainstream criteria extend to all triple-negative disease under 60 and any breast cancer under 40; CG164's 10 percent carrier-probability rule for everyone else. A pathogenic variant opens adjuvant olaparib (TA886), informs surgery, and starts cascade testing of relatives. | not mapped |