Treating itTriple-negative breast cancer (TNBC)

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.

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.

Pembrolizumab + chemotherapy (KEYNOTE-355) or sacituzumab govitecan + pembrolizumab (ASCENT-04, approved 2026).

Datopotamab deruxtecan (TROPION-Breast02, OS benefit) or sacituzumab govitecan (ASCENT-03), both approved 2026; PARP inhibitor if germline BRCA; chemotherapy.

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.

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.

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.

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.

Annual MRI from 30 to 49 and annual mammography from 40 to 69 for known BRCA1 or BRCA2 carriers (MRI sensitivity 77 percent against 40 percent for mammography in MARIBS); bilateral risk-reducing mastectomy for a small proportion of women from high-risk families after genetic counselling, cutting breast cancer risk by about 90 percent; tamoxifen or anastrozole are offered to women at high risk in general but did not reduce ER-negative breast cancer in the prevention trials.

TNM 8th edition with the AJCC prognostic stage note; sentinel node biopsy rather than axillary clearance to stage a clinically node-negative axilla (NG101 1.4); after neoadjuvant treatment the report gives pathological complete response or residual cancer burden, which drive the adjuvant choices in the residual-disease rows.

For most triple-negative cancers larger than 2 cm or with involved nodes, chemotherapy comes first (neoadjuvant): it can shrink the cancer so that breast-conserving surgery replaces a mastectomy, and the pathology report at surgery then shows how well it worked, which guides the treatment given afterwards. NICE NG101 (2025) says where neoadjuvant chemotherapy is indicated for triple-negative disease, offer a regimen containing a platinum, a taxane and an anthracycline, and discuss the trade-off: 85 rather than 81 out of 100 alive at 3 years with a platinum, against more neutropenic sepsis, low blood counts and anaemia. Very small node-negative cancers may go to surgery first, with chemotherapy afterwards decided on the final pathology. Macmillan: people with triple-negative breast cancer are more likely to have chemotherapy before surgery.

NICE TA851 recommends pembrolizumab with chemotherapy before surgery, then pembrolizumab alone for up to nine cycles after surgery, for triple-negative early breast cancer at high risk of recurrence or locally advanced disease (KEYNOTE-522: stage II to III). No PD-L1 test is needed at this stage: the trial's gain in complete responses (64.8% against 51.2%) and in survival (86.6% against 81.7% alive at 5 years) was seen whatever the PD-L1 result. The combined positive score of 10 or more decides pembrolizumab only for cancer that has spread. The cost is immune-related side effects, which can start at any time during or after treatment and occasionally leave a gland permanently underactive; carry the alert card and ring the 24-hour number for the symptoms on it.

The pathology report after neoadjuvant treatment is the strongest guide to what comes next. A pathological complete response (no invasive cancer left in breast or nodes) carries a good outlook and pembrolizumab simply continues. Residual disease is graded by residual cancer burden (RCB I to III); in triple-negative disease 10-year relapse-free survival fell from 86% after a complete response to 81%, 55% and 23% across the classes (Symmans 2017). For residual disease with a germline BRCA1 or BRCA2 variant, NICE TA886 recommends a year of olaparib (OlympiA: 4-year invasive disease-free survival 82.7% against 75.4%, with a survival gain). Without a BRCA variant, six to eight cycles of capecitabine is the usual offer (CREATE-X: 5-year survival 78.8% against 70.3% in triple-negative disease; hand-foot syndrome in 73%). Olaparib and capecitabine were not tested together, and there is no proven way to add both; trials, including ones guided by circulating tumour DNA, are the route beyond. The decision aid at /tools/tnbc-after-chemotherapy/ walks the report through these statements.

Breast-conserving surgery (wide local excision) followed by radiotherapy is usually as effective as mastectomy (Macmillan); mastectomy is advised when the cancer is large compared with the breast, there are several areas of cancer, or after earlier chest radiotherapy, and some people choose it. Chemotherapy first often makes conservation possible. Cancer at the margin means further surgery (NICE NG101: re-excise at 0 mm, consider within 1 mm). NICE says offer reconstruction to everyone having a mastectomy, offer both immediate and delayed options whether or not they are available locally, and offer immediate reconstruction even to those who may need radiotherapy; its table lists the trade-offs (implants more affected by radiotherapy than flaps; complications can delay chemotherapy or radiotherapy; more time to decide with delayed reconstruction). Some people prefer no reconstruction. The armpit is staged with a sentinel node biopsy (1 to 3 nodes); removing all the nodes raises the risk of lymphoedema and is reserved for involved nodes that need clearing.

After breast-conserving surgery the remaining breast is treated; after mastectomy the chest wall is treated when nodes were involved (macrometastases) or margins were involved, including after neoadjuvant chemotherapy where pretreatment tests showed involved nodes, and considered for node-negative T3 disease. NICE NG101 (2023): offer 26 Gy in 5 fractions over 1 week when the lymph nodes are not being treated (FAST-Forward: non-inferior to 40 Gy in 15 at 5 years), consider 40 Gy in 15 fractions over 3 weeks after implant reconstruction or where 3 weeks suits better, and offer 40 Gy in 15 fractions whenever regional nodes are irradiated (START-B). A boost to the tumour bed is offered where the risk of local recurrence is high. Partial-breast radiotherapy (IMPORT LOW) is reserved for low-risk ER-positive tumours in NICE's wording, so it rarely applies to triple-negative disease. Left-sided treatment often uses breath-hold to protect the heart. Skin reactions peak at the end and settle over 3 to 4 weeks.

Triple-negative breast cancer is more common under 40 and chemotherapy usually starts within weeks. NICE NG101 asks teams to advise everyone about options for preserving fertility and cross-refers to the NICE fertility guideline; Cancer Research UK says national guidelines expect the discussion at diagnosis. Options: embryo or egg freezing (about 2 to 3 weeks of ovarian stimulation, with random-start protocols to avoid delay), ovarian tissue freezing at a growing number of UK centres, and contraception during treatment because chemotherapy can damage eggs. NHS funding for freezing varies by area. Because this cancer has no hormone receptors there is no endocrine therapy to interrupt later; the question is protecting eggs before the first cycle, and asking early enough that the referral does not delay chemotherapy.

NICE NG101 says offer BRCA1 and BRCA2 testing to women under 50 with triple-negative breast cancer even with no family history; Breast Cancer Now says anyone diagnosed under 60 should be offered a referral to discuss testing, and the NHS test directory criteria that NICE points to for PARP inhibitor eligibility (R444.1) may make people over 60 eligible too. Testing is free on the NHS when a hospital specialist refers you, results take about 1 to 3 months, and a genetic counsellor helps with what the result means. A pathogenic variant: opens olaparib after chemotherapy for residual disease (NICE TA886) and a PARP inhibitor in metastatic disease; raises the question of risk-reducing surgery to the other breast and the ovaries, managed by a multidisciplinary team with counselling first (NICE CG164); and means each child has a 1 in 2 chance of carrying it, so relatives can be offered predictive testing. A variant of uncertain significance changes nothing yet. No variant found means relatives are not tested, though a strong family history may still raise risk.

Three results decide the first treatment for cancer that has spread, so ask that all three are back before the choice is made, ideally on a fresh biopsy because receptors can change: PD-L1 combined positive score (CPS 10 or more opens pembrolizumab with chemotherapy, NICE TA801, or with sacituzumab govitecan), germline BRCA status (a PARP inhibitor, olaparib or talazoparib), and HER2 score (1+ or 2+ without amplification, HER2-low, opens trastuzumab deruxtecan after chemotherapy). The TROP2 antibody-drug conjugates sacituzumab govitecan and datopotamab deruxtecan were approved first line in 2026 with different side-effect profiles; NHS funding follows NICE appraisals (sacituzumab govitecan is funded after two prior therapies under TA819), so ask what applies where you are treated. Ask for the palliative care team from the start, and think about a trial before the first line, because eligibility narrows with each treatment.

An antibody-drug conjugate carries chemotherapy into cells that show its target (TROP2 for sacituzumab govitecan and datopotamab deruxtecan, HER2 for trastuzumab deruxtecan), given as a drip in cycles: sacituzumab govitecan on days 1 and 8 of 21. The effects are still chemotherapy-like. Sacituzumab govitecan: low white cells (boxed warning; growth factor injections are sometimes used) and diarrhoea (boxed warning; Macmillan's rule is ring the 24-hour line for 4 or more stools a day, stools at night, or anti-diarrhoea medicine not working within 24 hours), plus sickness, tiredness and hair loss. Datopotamab deruxtecan: mouth soreness, eye problems (the label requires eye examinations) and rarely lung inflammation. Trastuzumab deruxtecan: interstitial lung disease in about 15% (2.2% fatal in the pooled analysis), mostly in the first year, so any new cough, breathlessness or fever is reported immediately; also sickness and low counts. Blood tests before each dose; doses are delayed or reduced rather than pushed through.

Triple-negative breast cancer spreads to the brain more often than other breast subtypes: about 29% of people with metastatic disease in a 433-patient series (25% within two years), and 46% before death in an older 116-patient series. For 1 to 3 metastases of a size suitable for radiosurgery, stereotactic radiosurgery alone is generally preferred: in a randomised trial it caused less cognitive decline at 3 months than radiosurgery plus whole-brain radiotherapy (63.5% against 91.7%) with no difference in survival. Whole-brain radiotherapy is kept for many or widespread metastases, with hippocampal-sparing planning and memantine where possible. Surgery is considered for a single large metastasis causing pressure. Drug treatment for the rest of the body usually continues; activity of the antibody-drug conjugates in the brain is emerging but unproven (the palliation term carries the ASCENT, real-world and DEBBRAH figures). Steroids relieve swelling in the short term. Ask what the plan is for symptoms (headache, seizures, weakness) and who to ring.

At every stage a trial can be a reasonable choice beside standard treatment: ask what the comparison arm is, whether a placebo is used (the NHS says only where no proven treatment exists; in KEYNOTE-522 the control arm had chemotherapy plus placebo, never placebo alone), what extra visits, tests and travel are involved and whether travel is paid, and that you can leave at any time without it affecting your care. Trials open to triple-negative breast cancer include ones testing less treatment after a complete response (OptimICE-pCR), anthracycline-free chemotherapy (SCARLET), circulating tumour DNA-guided escalation, and new antibody-drug conjugates in metastatic disease; the Triple Negative Breast Cancer Foundation and Cancer Research UK run trial finders. NICE NG101 asks teams to discuss research opportunities and encourage trial entry.

Carboplatin raises pathological complete response in every trial (GeparSixto 53.2 versus 36.9 percent, BrighTNess 58 versus 31, CALGB 40603) and improved disease-free survival in GeparSixto (hazard ratio 0.56) and event-free survival in BrighTNess (0.57) but not long-term outcomes in CALGB 40603 (not powered); it is part of the KEYNOTE-522 regimen and is standard in the UK. Adding veliparib to carboplatin added nothing (BrighTNess). Atezolizumab in place of pembrolizumab has no survival evidence (NeoTRIP, GeparDouze, ALEXANDRA).

About one in nine unselected triple-negative patients carries a germline BRCA1 or BRCA2 variant (11.2 percent, Couch 2015; 15.4 percent in a prospective registry, Sharma 2014; 17.2 percent in GeparSixto, Hahnen 2017); the testing rules are in the germline testing row. The result decides adjuvant olaparib (OlympiA, 82 percent triple-negative; NICE TA886), informs risk-reducing surgery, and in the UK offers PARTNER (olaparib with neoadjuvant carboplatin and paclitaxel, 30 sites). Platinum sensitivity is greatest in carriers (TNT: response 68 versus 33 percent with carboplatin versus docetaxel in metastatic disease).

Olaparib (OlympiAD: progression-free survival 7.0 versus 4.2 months, hazard ratio 0.58; no overall survival gain overall, hazard ratio 0.51 in patients untreated for metastatic disease; NICE TA1040) or talazoparib (EMBRACA: 8.6 versus 5.6 months, hazard ratio 0.54; final overall survival hazard ratio 0.85; NICE TA952), with the lower-cost option first in England; a platinum doublet is the alternative (BROCADE3 control arm median survival 28.2 months); PARP inhibitor added to chemotherapy (veliparib, BROCADE3) improved progression-free but not overall survival and is not licensed. Sequence relative to PD-1 or TROP2 ADC first-line therapy is untested.

Trastuzumab deruxtecan 5.4 mg/kg every 3 weeks (DESTINY-Breast04: overall survival 23.4 versus 16.8 months in all patients, hazard ratio 0.64; hormone-receptor-negative cohort of 63, progression-free survival 8.5 versus 2.9 months, hazard ratio 0.46; interstitial lung disease 12.1 percent, 0.8 percent fatal). Licensed in the US (2022) and EU (2023) for HER2-low regardless of hormone receptor status; not recommended by NICE (TA992, 29 July 2024; rapid review in development), so not commissioned in England. HER2-ultralow triple-negative disease has no licensed indication.

Single-fraction radiotherapy for painful bone metastases with denosumab or zoledronic acid to reduce skeletal events; urgent radiotherapy or surgery for spinal cord compression; drainage with talc pleurodesis or an indwelling catheter for malignant pleural effusion; radiotherapy and wound care for chest wall recurrence; management of drug toxicities (hand-foot syndrome on capecitabine, neutropenia and diarrhoea on sacituzumab govitecan, stomatitis and eye symptoms on datopotamab deruxtecan, interstitial lung disease on trastuzumab deruxtecan); early integrated palliative care from diagnosis of metastatic disease.