{"entity":{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","aka":["TNBC evidence roadmap","Basal-like breast cancer roadmap","Triple-negative breast cancer history"],"tldr":"Triple-negative breast cancer was named for what it lacks, the three receptors other breast cancers are treated through. This roadmap follows it from the receptor discoveries and the basal-like signature of 2000, through chemotherapy, platinum, PARP inhibitors, immunotherapy and antibody-drug conjugates, to the trials asking who can have less and who needs more, with registry dates to 2030.","summary":"For most of its history triple-negative breast cancer was a remainder. Oestrogen receptor testing, then HER2 (Slamon 1987), sorted breast cancers into those with a target; the tumours negative for all three were left with chemotherapy alone. Gene expression profiling gave the remainder a biology (Perou 2000; Sørlie 2001, 2003), linked it to germline BRCA1 (Sørlie 2003; Foulkes 2003; Atchley 2008) and to the founder mutations that concentrate hereditary disease in particular populations (Struewing 1997; Górski 2000), and registry studies of 2006 to 2007 gave it a name, a natural history (relapse peaking at three years, then subsiding) and a demography: younger women, Black and Hispanic women, poorer women, worse survival at every stage. In the United Kingdom the POSH cohort found the same excess in young Black women within a health service with equal access.\n\nChemotherapy was the whole of treatment until 2017, and it worked: anthracycline and taxane regimens cut breast cancer deaths by a third (EBCTCG 2012), tumours disappeared before surgery twice as often as in other subtypes (Liedtke 2008), and those that disappeared were largely cured (Cortazar 2014). Residual disease was the problem, graded from 2007 by the residual cancer burden score. Platinum raised the response rate (GeparSixto and CALGB 40603, 2014 to 2015) and later relapse-free survival (BrighTNess, GeparSixto follow-up), and capecitabine after residual disease became the first post-neoadjuvant treatment (CREATE-X 2017). Molecular subtyping (Lehmann 2011, 2016; Burstein 2015) showed the disease was several diseases, but pathway-targeted small molecules failed, most recently the AKT inhibitor capivasertib (CAPItello-290, 2026).\n\nThree classes then arrived in six years. PARP inhibitors for germline BRCA carriers (OlympiAD, EMBRACA 2017 to 2018; OlympiA 2021, with a survival benefit sustained at six years). Immunotherapy: atezolizumab first (IMpassion130, 2018, later withdrawn after IMpassion131 and an assay dispute), then pembrolizumab first line for PD-L1 combined positive score of 10 or more (KEYNOTE-355) and before and after surgery for stage II to III disease (KEYNOTE-522, with a 4.9-point overall survival gain at five years, 86.6 against 81.7 percent, reported in 2024). Antibody-drug conjugates: sacituzumab govitecan after two lines (ASCENT 2021), trastuzumab deruxtecan for the third of triple-negative tumours that are HER2-low (DESTINY-Breast04, 2022), then first line for all comers (ASCENT-03, ASCENT-04, TROPION-Breast02, 2025 to 2026), with median survival approaching two years against 13 months in 2008.\n\nThe open questions are now about selection and quantity. Who can have less: pembrolizumab omission after pathological complete response (OptimICE-pCR), anthracycline omission (SCARLET), chemotherapy omission in lymphocyte-rich stage I tumours. Who needs more: residual disease trials with antibody-drug conjugates (ASCENT-05, TROPION-Breast03) and the ctDNA-guided designs that c-TRAK TN showed must test earlier and more sensitively. And what the trials have not settled: PD-L1 assay concordance, the order of two topoisomerase-payload antibody-drug conjugates, brain metastases in half of metastatic patients, HER2-low scoring reproducibility, and a disparity in incidence and outcome that trial enrolment has not reflected. UK and NHS specifics are on the UK and NHS page for triple-negative breast cancer.","asOf":"2026-09-24","links":[{"label":"Slamon et al.: HER-2/neu amplification and survival in breast cancer (Science 1987)","url":"https://europepmc.org/article/MED/3798106"},{"label":"Perou et al.: molecular portraits of human breast tumours (Nature 2000)","url":"https://europepmc.org/article/MED/10963602"},{"label":"Sorlie et al.: repeated observation of breast tumour subtypes; BRCA1 predisposes to the basal subtype (PNAS 2003)","url":"https://europepmc.org/article/MED/12829800"},{"label":"Struewing et al.: cancer risk of BRCA1 and BRCA2 founder mutations among Ashkenazi Jews (NEJM 1997)","url":"https://europepmc.org/article/MED/9145676"},{"label":"Dent et al.: triple-negative breast cancer, clinical features and patterns of recurrence (Clin Cancer Res 2007)","url":"https://europepmc.org/article/MED/17671126"},{"label":"Carey et al.: race, breast cancer subtypes and survival in the Carolina Breast Cancer Study (JAMA 2006)","url":"https://europepmc.org/article/MED/16757721"},{"label":"Copson et al.: ethnicity and outcome of young breast cancer patients in the UK, the POSH study (Br J Cancer 2014)","url":"https://europepmc.org/article/MED/24149174"},{"label":"Lehmann et al.: identification of human triple-negative breast cancer subtypes (J Clin Invest 2011)","url":"https://europepmc.org/article/MED/21633166"},{"label":"EBCTCG: polychemotherapy regimens for early breast cancer, 100,000 women in 123 trials (Lancet 2012)","url":"https://europepmc.org/article/MED/22152853"},{"label":"Cortazar et al.: pathological complete response and long-term benefit, CTNeoBC pooled analysis (Lancet 2014)","url":"https://europepmc.org/article/MED/24529560"},{"label":"CREATE-X: adjuvant capecitabine after preoperative chemotherapy (NEJM 2017)","url":"https://europepmc.org/article/MED/28564564"},{"label":"OlympiA six-year update: sustained benefit of adjuvant olaparib (Ann Oncol 2026)","url":"https://europepmc.org/article/MED/42636977"},{"label":"Rugo et al.: PD-L1 assay comparison in IMpassion130 (J Natl Cancer Inst 2021)","url":"https://europepmc.org/article/MED/34097070"},{"label":"Leon-Ferre et al.: tumour-infiltrating lymphocytes in triple-negative breast cancer treated without chemotherapy (JAMA 2024)","url":"https://europepmc.org/article/MED/38563834"},{"label":"c-TRAK TN: ctDNA surveillance and pembrolizumab in early triple-negative breast cancer (Ann Oncol 2023)","url":"https://europepmc.org/article/MED/36423745"},{"label":"TROPION-Breast02: datopotamab deruxtecan first line (Ann Oncol 2026)","url":"https://europepmc.org/article/MED/41937088"},{"label":"CAPItello-290: capivasertib plus paclitaxel first line (Ann Oncol 2026)","url":"https://europepmc.org/article/MED/41422862"},{"label":"ESMO Clinical Practice Guideline: early breast cancer (Ann Oncol 2024)","url":"https://europepmc.org/article/MED/38101773"},{"label":"St Gallen 2025 consensus on early breast cancer (Ann Oncol 2025)","url":"https://europepmc.org/article/MED/41072918"},{"label":"ClinicalTrials.gov NCT03036488","url":"https://clinicaltrials.gov/study/NCT03036488"},{"label":"ClinicalTrials.gov NCT02032823","url":"https://clinicaltrials.gov/study/NCT02032823"},{"label":"ClinicalTrials.gov NCT05374512","url":"https://clinicaltrials.gov/study/NCT05374512"},{"label":"ClinicalTrials.gov NCT03997123","url":"https://clinicaltrials.gov/study/NCT03997123"},{"label":"ClinicalTrials.gov NCT05812807","url":"https://clinicaltrials.gov/study/NCT05812807"},{"label":"ClinicalTrials.gov NCT05929768","url":"https://clinicaltrials.gov/study/NCT05929768"},{"label":"ClinicalTrials.gov NCT05633654","url":"https://clinicaltrials.gov/study/NCT05633654"},{"label":"ClinicalTrials.gov NCT05629585","url":"https://clinicaltrials.gov/study/NCT05629585"},{"label":"ClinicalTrials.gov NCT06103864","url":"https://clinicaltrials.gov/study/NCT06103864"},{"label":"ClinicalTrials.gov NCT06926868","url":"https://clinicaltrials.gov/study/NCT06926868"},{"label":"ClinicalTrials.gov NCT06382142","url":"https://clinicaltrials.gov/study/NCT06382142"},{"label":"ClinicalTrials.gov NCT06419621","url":"https://clinicaltrials.gov/study/NCT06419621"}],"tags":["tnbc","breast","roadmap"],"related":["tnbc-history","trop2-adc-roadmap","adc-generations","immunotherapy-roadmap","chemotherapy-roadmap","targeted-therapy-roadmap","ctdna-tests","platinum-plus-hrd","germline-to-parp","idea-tnbc-de-escalation-for-exceptional-responders","idea-tnbc-ctdna-guided-adjuvant-decisions","idea-tnbc-disparities-in-access-and-outcomes","idea-tnbc-pd-l1-assay-harmonisation","idea-tnbc-adc-sequencing-trial","idea-tnbc-brain-metastasis-trials","idea-tnbc-her2-ultralow-testing-uptake","idea-tnbc-uk-trial-access-and-germline-testing-audit","idea-tnbc-uk-ethnicity-stratified-outcome-reporting"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive","her2-low-metastatic-breast-cancer"],"sections":["adcs","immunotherapy","chemotherapy","targeted-therapy"],"technologies":["adc","bispecific-adc","checkpoint-inhibitor","parp-inhibitor","platinum","liquid-biopsy","mrd-testing","germline-testing","digital-pathology-ai","rna-seq","trop2-pet"],"targets":["trop2","pdl1","her2","brca","androgen-receptor","akt"],"drugs":["pembrolizumab","atezolizumab","sacituzumab-govitecan","datopotamab-deruxtecan","trastuzumab-deruxtecan","izalontamab-brengitecan","olaparib","talazoparib","capecitabine","carboplatin","paclitaxel","nab-paclitaxel","doxorubicin","cyclophosphamide","capivasertib","ventana-pd-l1-sp142","signatera"],"companies":["merck","gilead","astrazeneca","daiichi-sankyo","roche-genentech","pfizer","bms","systimmune"],"institutions":["unc-lineberger","md-anderson","dana-farber","gbg","royal-marsden","mayo-clinic","nci","cruk","esmo","asco"],"pathways":["ddr","emt","pi3k-akt-mtor","pd1-checkpoint"],"terms":["pcr","rcb","tils","cps","hrd","her2-low","her2-ultralow","ctdna","mrd","de-escalation","neoadjuvant-adjuvant","germline-testing","brain-metastases","adc-sequencing","adc-after-adc-caution","pam50","anthracycline","taxane","efs","os","pfs"],"trials":["keynote-522","keynote-355","impassion130","impassion131","impassion031","ascent","ascent-03","ascent-04","ascent-05","olympia","olympiad","embraca","brightness","geparsixto","tropion-breast01","tropion-breast02","tropion-breast03","tropion-breast05","destiny-breast04","optimice-pcr","scarlet-s2212","izabright-breast01","bl-b01d1-307","nct03997123","nct06419621"],"people":["peter-schmid","javier-cortes","rebecca-dent","hope-rugo","sibylle-loibl","charles-perou","judy-garber","andrew-tutt","nicholas-turner","sara-tolaney","aditya-bardia","jennifer-litton","mark-robson","lajos-pusztai","nancy-lin","giuseppe-curigliano","charles-geyer","gunter-von-minckwitz","mary-claire-king","richard-peto"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-trial-diversity","b-resistance","b-brain-delivery","b-toxicity-qol","b-hereditary-risk","b-tumor-heterogeneity","b-immunotherapy-response","b-negative-results"],"keyPapers":["paper-slamon-her2-amplification-science-1987","paper-perou-molecular-portraits-breast-tumours-nature-2000","paper-sorlie-repeated-observation-subtypes-brca1-basal-pnas-2003","paper-struewing-brca-founder-mutations-ashkenazi-nejm-1997","paper-dent-tnbc-clinical-features-recurrence-ccr-2007","paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006","paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014","paper-lehmann-tnbc-subtypes-jci-2011","paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014","paper-symmans-j-clin-oncol","paper-yau-rcb-pooled-analysis-5161-lancet-oncol-2022","paper-geparsixto-lancet-oncol-2014","paper-create-x-adjuvant-capecitabine-nejm-2017","paper-olympiad-nejm-2017","paper-embraca-n-engl-j-med-2018","paper-olympia-nejm-2021","paper-olympia-6-year-update-ann-oncol-2026","paper-impassion130-n-engl-j-med-2018","paper-impassion131-ann-oncol-2021","paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","paper-keynote-355-nejm-2022","paper-keynote-522-n-engl-j-med-2020","paper-keynote-522-n-engl-j-med-2024-update","paper-ascent-nejm-2021","paper-destiny-breast04-nejm-2022","paper-tropion-breast02-ann-oncol-2026","paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026","paper-leon-ferre-tils-tnbc-no-chemotherapy-jama-2024","paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","paper-esmo-early-breast-cancer-guideline-ann-oncol-2024","paper-nccn-breast-cancer-v4-2026-jnccn-2026","paper-st-gallen-2025-consensus-ann-oncol-2025"],"journals":[],"dependsOn":[],"notes":["How this stays current: scripts/roadmap-watch.ts (npm run roadmap:watch) checks each trial here against ClinicalTrials.gov and searches Europe PMC for new papers on the acronyms since asOf. Anything it prints that this page does not say is an edit to make; then move asOf forward.","Dates in 'What to watch' are quoted from the registry as read on 2026-09-24 and are not predictions; estimated completion dates move.","The primary papers of the pivotal trials (KEYNOTE-522, KEYNOTE-355, IMpassion130 and 131, ASCENT, DESTINY-Breast04, OlympiA, OlympiAD, EMBRACA, BrighTNess, GeparSixto) are linked from the steps to their existing records; this deep dive adds the guideline, discovery, disparity, residual disease and 2026 trial papers around them.","UK and NHS specifics (referral routes, NICE positions, Cancer Drugs Fund status, germline testing criteria, trial access) are held on the UK and NHS page for triple-negative breast cancer and are not restated here."],"steps":[{"era":"1987-2010","title":"Defined by three negative tests","description":"Oestrogen receptor assays sorted breast cancers into those that would respond to endocrine therapy and those that would not; in 1987 Slamon and colleagues found HER-2/neu amplified in 30 percent of 189 tumours and predictive of early relapse, adding a third test. The tumours negative for all three were a remainder with chemotherapy as their only treatment. The thresholds that define the remainder are conventions: the 2010 ASCO and CAP guideline fixed oestrogen and progesterone receptor positivity at 1 percent of nuclei after finding up to 20 percent of tests worldwide might be wrong, and the 1 to 10 percent low-positive band it created still behaves like triple-negative disease in many series.","refs":["paper-slamon-her2-amplification-science-1987","paper-asco-cap-er-pr-testing-guideline-jco-2010","her2","ihc","tnbc"],"status":"historic"},{"era":"2000-2003","title":"The basal-like subtype and its link to BRCA1","description":"Perou and colleagues read 8,102 genes in 65 tumours in 2000 and found breast cancer fell into groups, one of them basal epithelial-like; Sørlie showed in 2001 that the basal-like group had the worst outcome and in 2003 that the subtypes reproduced in other laboratories' data and that tumours from BRCA1 carriers fell into the basal group. Foulkes confirmed the BRCA1 link the same year with a cytokeratin 5/6 stain (odds ratio 9.0). The remainder now had a biology and a hereditary cause; basal-like and triple-negative overlap but are not the same set.","refs":["paper-perou-molecular-portraits-breast-tumours-nature-2000","paper-sorlie-breast-carcinoma-subclasses-pnas-2001","paper-sorlie-repeated-observation-subtypes-brca1-basal-pnas-2003","paper-foulkes-brca1-basal-phenotype-jnci-2003","charles-perou","pam50","rna-seq","brca"],"status":"historic"},{"era":"1997-2008","title":"Founder mutations: hereditary disease has a geography","description":"Struewing's 1997 study of 5,318 Ashkenazi Jewish volunteers put the breast cancer risk of the three founder mutations carried by over 2 percent of that population at 56 percent by age 70; Górski found in 2000 that three BRCA1 changes accounted for 82 percent of the mutations in 66 Polish families, one of them (5382insC) shared with the Ashkenazi set. Atchley's 2008 MD Anderson series showed 57 percent of BRCA1 carriers' tumours were triple-negative against 14 percent in non-carriers, which made a triple-negative diagnosis itself a reason to test. Founder panels make population testing cheap where they exist; where they do not, full sequencing is needed and uptake lags.","refs":["paper-struewing-brca-founder-mutations-ashkenazi-nejm-1997","paper-gorski-brca1-founder-mutations-poland-ajhg-2000","paper-atchley-brca-status-triple-negative-jco-2008","paper-asco-hereditary-breast-cancer-guideline-jco-2020","germline-testing","brca","mary-claire-king","b-hereditary-risk","idea-tnbc-uk-trial-access-and-germline-testing-audit"],"status":"historic"},{"era":"2006-2008","title":"A name, a natural history and a disparity","description":"Dent's Toronto cohort (2007) found triple-negative disease in 11.2 percent of 1,601 patients with a distant relapse hazard ratio of 2.6 that peaked at three years and faded after five; Bauer's California registry study (2007) of 6,370 cases fixed its demography as younger, Black, Hispanic and poorer women with worse survival at every stage. Carey's Carolina Breast Cancer Study (2006) had found the basal-like subtype in 39 percent of premenopausal African American women against 16 percent of others, and Lin (2008) showed 46 percent of metastatic patients developed brain metastases with a median survival of 13.3 months. National counts followed: 12.2 percent of US cases in 2010 (Howlader 2014), odds ratio 2.27 for Black women in 1.15 million cases (Scott 2019). In the UK the POSH cohort of women under 41 found 26.1 percent triple-negative disease in Black women against 18.6 percent in White women and five-year survival of 71.1 versus 82.4 percent despite equal chemotherapy use.","refs":["paper-dent-tnbc-clinical-features-recurrence-ccr-2007","paper-bauer-triple-negative-california-registry-cancer-2007","paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006","paper-lin-tnbc-cns-metastases-dfci-cancer-2008","paper-howlader-us-incidence-breast-subtypes-jnci-2014","paper-scott-tnbc-disparities-uscs-cancer-2019","paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014","rebecca-dent","nancy-lin","brain-metastases","b-trial-diversity","idea-tnbc-disparities-in-access-and-outcomes","idea-tnbc-brain-metastasis-trials"],"status":"historic"},{"era":"1990s-2014","title":"Anthracycline and taxane chemotherapy, and the residual disease paradox","description":"The Oxford overview of 123 trials (EBCTCG 2012) showed taxane-plus-anthracycline regimens cut breast cancer deaths by about a third regardless of receptor status, so chemotherapy's absolute benefit was largest in the high-risk remainder. Liedtke's MD Anderson series (2008) found triple-negative tumours disappeared completely before surgery twice as often as others (22 versus 11 percent) yet survival was worse, because women with residual disease relapsed early. Symmans graded residual disease with the residual cancer burden score in 2007; the CTNeoBC pooled analysis (2014) found pathological complete response predicted survival most strongly in triple-negative disease (event-free survival hazard ratio 0.24) but could not validate it as a trial-level surrogate. The US regulator nonetheless built an accelerated approval pathway on it.","refs":["paper-ebctcg-polychemotherapy-regimens-meta-analysis-lancet-2012","paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","paper-symmans-j-clin-oncol","paper-symmans-rcb-long-term-prognosis-subtype-jco-2017","paper-yau-rcb-pooled-analysis-5161-lancet-oncol-2022","paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014","paper-asco-neoadjuvant-therapy-breast-guideline-jco-2021","anthracycline","taxane","pcr","rcb","neoadjuvant-adjuvant","chemotherapy"],"status":"historic"},{"era":"2011-2016","title":"Several diseases: molecular subtypes","description":"Lehmann's 2011 analysis of 587 tumours defined six subtypes (basal-like 1 and 2, immunomodulatory, mesenchymal, mesenchymal stem-like, luminal androgen receptor), each with candidate drugs from cell line work; the 2016 refinement showed two came from immune and stromal cells, cut the scheme to four, and found pathological complete response ranged from 41 percent in basal-like 1 to 18 percent in basal-like 2. Burstein's Baylor study (2015) reached a similar four-way split and showed immune activation within basal-like tumours separated good from poor prognosis. The subtypes shaped trial design (androgen receptor antagonists for the luminal androgen receptor group, platinum for basal-like 1) but no subtype-directed small molecule has succeeded in phase 3.","refs":["paper-lehmann-tnbc-subtypes-jci-2011","paper-lehmann-tnbctype-4-refinement-plos-one-2016","paper-burstein-tnbc-genomic-subtypes-ccr-2015","androgen-receptor","emt","ddr","b-tumor-heterogeneity"],"status":"historic"},{"era":"2014-2022","title":"Platinum","description":"GeparSixto (2014) and CALGB 40603 (2015) showed carboplatin raised pathological complete response, in CALGB 40603 from 41 to 54 percent in breast and axilla. Survival followed: GeparSixto's final analysis (2018) gave a disease-free survival hazard ratio of 0.56 in triple-negative disease and found 70 percent of tumours homologous recombination deficient whether or not BRCA was mutated, with the deficiency predicting response but not carboplatin benefit; BrighTNess at 4.5 years (2022) gave an event-free survival hazard ratio of 0.57 for carboplatin over paclitaxel alone and nothing for added veliparib. The TNT trial showed carboplatin's advantage in metastatic disease was confined to germline BRCA carriers. St Gallen 2025 made platinum a consensus recommendation for early triple-negative disease.","refs":["geparsixto","paper-geparsixto-lancet-oncol-2014","paper-loibl-geparsixto-survival-hrd-ann-oncol-2018","paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015","brightness","paper-brightness-lancet-oncol-2018","paper-geyer-brightness-4-year-follow-up-ann-oncol-2022","paper-tutt-nat-med","paper-st-gallen-2025-consensus-ann-oncol-2025","carboplatin","platinum","hrd","platinum-plus-hrd","sibylle-loibl","gbg"],"status":"current"},{"era":"2017","title":"Residual disease becomes treatable: capecitabine after neoadjuvant chemotherapy","description":"CREATE-X randomised 910 Japanese and Korean women with HER2-negative residual disease after neoadjuvant chemotherapy to six months of capecitabine or nothing: five-year overall survival 89.2 versus 83.6 percent (hazard ratio 0.59), and in the triple-negative group 78.8 versus 70.3 percent (0.52), with hand-foot syndrome in 73 percent. It was the first proof that the post-neoadjuvant window could be used, the design OlympiA, ASCENT-05 and TROPION-Breast03 inherited, and capecitabine remains the option for residual disease without a BRCA variant in ESMO, NCCN and UK practice. Whether it adds to adjuvant pembrolizumab has never been tested.","refs":["paper-create-x-adjuvant-capecitabine-nejm-2017","capecitabine","rcb","neoadjuvant-adjuvant","paper-esmo-early-breast-cancer-guideline-ann-oncol-2024","idea-tnbc-ctdna-guided-adjuvant-decisions"],"status":"current"},{"era":"2017-2026","title":"PARP inhibition for germline BRCA carriers","description":"OlympiAD (2017) and EMBRACA (2018) showed olaparib and talazoparib beat chemotherapy for progression-free survival in metastatic germline BRCA-mutated breast cancer, without a clear survival gain. OlympiA (2021) gave a year of adjuvant olaparib to 1,836 high-risk carriers, 82 percent with triple-negative disease, and improved invasive disease-free survival; the 2022 analysis showed an overall survival hazard ratio of 0.68 and the 2026 six-year update 0.72 (six-year survival 87.5 versus 83.2 percent) with no excess of leukaemia and fewer new BRCA-related cancers. Neoadjuvant PARP inhibition in unselected disease failed (BrighTNess veliparib arm). The 2020 ASCO, ASTRO and SSO hereditary guideline sets the surgical and systemic rules for carriers; whether olaparib adds to pembrolizumab or capecitabine in the same patient is untested.","refs":["olympiad","paper-olympiad-nejm-2017","embraca","paper-embraca-n-engl-j-med-2018","olympia","paper-olympia-nejm-2021","paper-olympia-overall-survival-ann-oncol-2022","paper-olympia-6-year-update-ann-oncol-2026","paper-asco-hereditary-breast-cancer-guideline-jco-2020","olaparib","talazoparib","parp-inhibitor","brca","germline-testing","germline-to-parp","judy-garber","andrew-tutt","mark-robson","jennifer-litton","astrazeneca","pfizer"],"status":"current"},{"era":"2018-2024","title":"Immunotherapy: an assay dispute, then a new standard for early disease","description":"IMpassion130 (2018) showed atezolizumab with nab-paclitaxel lengthened progression-free survival in PD-L1-positive metastatic disease by the SP142 assay; IMpassion131 with paclitaxel was negative, the US indication was withdrawn in 2021, and Rugo's assay comparison showed SP142, SP263 and 22C3 called 46, 75 and 73 percent of the same tumours positive with 69 percent concordance. KEYNOTE-355 (2020, survival 2022) established pembrolizumab with chemotherapy for 22C3 combined positive score of 10 or more. KEYNOTE-522 (2020) added pembrolizumab before and after surgery for stage II to III disease: pathological complete response 64.8 versus 51.2 percent, event-free survival gain in 2022, and in 2024 a 4.9-point five-year overall survival gain (86.6 against 81.7 percent), the first survival benefit of immunotherapy in early breast cancer. ASCO reversed its 2021 guideline within 15 months; ESMO, NCCN and St Gallen followed. Leon-Ferre (2024) showed lymphocyte-rich stage I tumours do well without any chemotherapy, and OptimICE-pCR now asks whether adjuvant pembrolizumab can be dropped after complete response.","refs":["impassion130","paper-impassion130-n-engl-j-med-2018","impassion131","paper-impassion131-ann-oncol-2021","paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","keynote-355","paper-keynote-355-nejm-2022","keynote-522","paper-keynote-522-n-engl-j-med-2020","paper-keynote-522-nejm-2022","paper-keynote-522-n-engl-j-med-2024-update","paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022","paper-leon-ferre-tils-tnbc-no-chemotherapy-jama-2024","optimice-pcr","pembrolizumab","atezolizumab","checkpoint-inhibitor","cps","tils","pdl1","peter-schmid","javier-cortes","hope-rugo","merck","roche-genentech","immunotherapy","idea-tnbc-pd-l1-assay-harmonisation","idea-tnbc-de-escalation-for-exceptional-responders"],"status":"current"},{"era":"2020-2026","title":"Antibody-drug conjugates move from third line to first","description":"ASCENT (2021) doubled survival with sacituzumab govitecan after two or more lines (12.1 versus 6.7 months); DESTINY-Breast04 (2022) showed trastuzumab deruxtecan worked in HER2-low tumours, which are 36.6 percent of triple-negative disease though biologically indistinguishable from HER2-zero (Schettini 2021). ASCENT-03 and ASCENT-04 (2025 to 2026) and TROPION-Breast02 (2026: progression-free survival 10.8 versus 5.6 months, overall survival 23.7 versus 18.7) moved TROP2 antibody-drug conjugates to first line, alone or with pembrolizumab, and the bispecific EGFR and HER3 conjugate izalontamab brengitecan posted a positive phase 3 in pretreated disease. The same year the AKT inhibitor capivasertib failed to improve survival first line (CAPItello-290), the latest pathway-targeted small molecule to do so. Median survival in first-line trials now approaches two years against 13.3 months in the 2008 Dana-Farber series.","refs":["ascent","paper-ascent-nejm-2021","destiny-breast04","paper-destiny-breast04-nejm-2022","paper-schettini-her2-low-features-npj-breast-cancer-2021","ascent-03","paper-ascent-03-n-engl-j-med-2025","ascent-04","paper-ascent-04-n-engl-j-med-2026","tropion-breast02","paper-tropion-breast02-ann-oncol-2026","bl-b01d1-307","nct03997123","paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026","sacituzumab-govitecan","datopotamab-deruxtecan","trastuzumab-deruxtecan","izalontamab-brengitecan","capivasertib","trop2","her2-low","adc","bispecific-adc","trop2-adc-roadmap","adc-generations","rebecca-dent","aditya-bardia","sara-tolaney","gilead","astrazeneca","daiichi-sankyo","adcs","idea-tnbc-adc-sequencing-trial","idea-tnbc-her2-ultralow-testing-uptake"],"status":"current"},{"era":"2020-2026","title":"Residual disease and the blood test that might guide it","description":"Radovich (2020) showed ctDNA after neoadjuvant chemotherapy in 142 residual-disease patients carried a distant relapse hazard ratio of 2.99 and a death hazard ratio of 4.16. The UK c-TRAK TN trial (2023) then tested acting on it: 27 percent of 161 women turned ctDNA-positive within a year, but 72 percent of those already had metastases on staging and none of five given pembrolizumab cleared their DNA, so later designs test earlier, with tumour-informed assays, and use drugs with more single-agent activity. Meanwhile the residual cancer burden score, validated across 5,161 patients (Yau 2022), became the entry criterion for antibody-drug conjugate trials after neoadjuvant therapy: ASCENT-05 (sacituzumab govitecan with pembrolizumab, 1,514 patients) and TROPION-Breast03 (datopotamab deruxtecan with or without durvalumab, 1,174 patients).","refs":["paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020","paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","paper-yau-rcb-pooled-analysis-5161-lancet-oncol-2022","ascent-05","tropion-breast03","ctdna","mrd","rcb","liquid-biopsy","mrd-testing","signatera","ctdna-tests","nicholas-turner","royal-marsden","b-dormancy-mrd","idea-tnbc-ctdna-guided-adjuvant-decisions"],"status":"emerging"},{"era":"2026-2030","title":"What the registry says is coming","description":"The de-escalation trials are large and slow: OptimICE-pCR (pembrolizumab versus observation after pathological complete response, 1,295 estimated, primary completion May 2033) and SCARLET (anthracycline-free chemo-immunotherapy, 2,400 estimated, March 2033). The escalation trials report sooner: ASCENT-05 (June 2027) and TROPION-Breast03 (September 2027) for residual disease. First-line combinations follow: TROPION-Breast05 (datopotamab deruxtecan with durvalumab against chemotherapy with pembrolizumab in PD-L1-positive disease, 625 estimated, July 2027), IZABRIGHT-Breast01 (izalontamab brengitecan first line in immunotherapy-ineligible disease, 600, March 2028) and the PD-L1 and VEGF bispecific PM8002 with nab-paclitaxel (392, July 2027). KEYNOTE-522 completed on the registry in October 2025; OlympiA's study completion is listed for May 2029.","refs":["optimice-pcr","scarlet-s2212","ascent-05","tropion-breast03","tropion-breast05","izabright-breast01","nct06419621","keynote-522","olympia","de-escalation","idea-tnbc-de-escalation-for-exceptional-responders","idea-tnbc-ctdna-guided-adjuvant-decisions"],"status":"emerging"},{"era":"What sets the pace","title":"Selection, sequence, sanctuary and who gets enrolled","description":"Four things the trials have not settled. PD-L1 assays disagree on a quarter of patients and only one, 22C3 combined positive score of 10, has an approved drug attached. Two TROP2 antibody-drug conjugates and trastuzumab deruxtecan share a topoisomerase I payload and no randomised trial has asked which to give first or whether the second works after the first. Brain metastases occur in about half of metastatic patients (Lin 2008) and most trials exclude active brain disease. And the disease is twice as common in Black women in the United States, with worse survival in the UK POSH cohort despite equal access, yet trial enrolment does not reflect it. Each has an idea on this page; the UK-specific gaps are set out on the UK and NHS page for triple-negative breast cancer.","refs":["paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","paper-lin-tnbc-cns-metastases-dfci-cancer-2008","paper-scott-tnbc-disparities-uscs-cancer-2019","paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014","adc-sequencing","adc-after-adc-caution","brain-metastases","b-biomarker-validation","b-resistance","b-brain-delivery","b-trial-diversity","idea-tnbc-pd-l1-assay-harmonisation","idea-tnbc-adc-sequencing-trial","idea-tnbc-brain-metastasis-trials","idea-tnbc-disparities-in-access-and-outcomes","idea-tnbc-uk-ethnicity-stratified-outcome-reporting"],"status":"current"}],"watch":[{"item":"TROPION-Breast02 study completion on the registry (datopotamab deruxtecan first line, immunotherapy-ineligible; primary completion 25 August 2025, actual)","expected":"2026-12-31","source":"https://clinicaltrials.gov/study/NCT05374512","refs":["tropion-breast02","datopotamab-deruxtecan"]},{"item":"CAPItello-290 study completion on the registry (capivasertib plus paclitaxel first line; published negative for overall survival in 2026)","expected":"2026-03-16","source":"https://clinicaltrials.gov/study/NCT03997123","refs":["nct03997123","capivasertib","paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026"]},{"item":"ASCENT-05 / OptimICE-RD primary completion: sacituzumab govitecan with pembrolizumab vs physician's choice for residual invasive disease after neoadjuvant therapy (1,514 estimated participants)","expected":"2027-06","source":"https://clinicaltrials.gov/study/NCT05633654","refs":["ascent-05","sacituzumab-govitecan","pembrolizumab","rcb"]},{"item":"TROPION-Breast05 primary completion: datopotamab deruxtecan with or without durvalumab vs chemotherapy with pembrolizumab, first line, PD-L1-positive (625 estimated participants)","expected":"2027-07-28","source":"https://clinicaltrials.gov/study/NCT06103864","refs":["tropion-breast05","datopotamab-deruxtecan","cps"]},{"item":"PM8002 (PD-L1 and VEGF bispecific) plus nab-paclitaxel vs placebo plus nab-paclitaxel, first line: primary completion (392 estimated participants)","expected":"2027-07","source":"https://clinicaltrials.gov/study/NCT06419621","refs":["nct06419621","nab-paclitaxel"]},{"item":"TROPION-Breast03 primary completion: datopotamab deruxtecan with or without durvalumab vs investigator's choice for stage I to III disease without pathological complete response (1,174 participants; active, not recruiting)","expected":"2027-09-20","source":"https://clinicaltrials.gov/study/NCT05629585","refs":["tropion-breast03","datopotamab-deruxtecan","rcb"]},{"item":"BL-B01D1-307 / PANKU-Breast02 study completion (izalontamab brengitecan vs chemotherapy in pretreated disease; primary completion 13 January 2026, actual)","expected":"2027-12","source":"https://clinicaltrials.gov/study/NCT06382142","refs":["bl-b01d1-307","izalontamab-brengitecan"]},{"item":"IZABRIGHT-Breast01 primary completion: izalontamab brengitecan vs chemotherapy, first line, anti-PD-(L)1-ineligible (600 estimated participants)","expected":"2028-03-13","source":"https://clinicaltrials.gov/study/NCT06926868","refs":["izabright-breast01","izalontamab-brengitecan","bispecific-adc"]},{"item":"OlympiA study completion on the registry (adjuvant olaparib; primary completion 27 March 2020, actual; six-year update published 2026)","expected":"2029-05-28","source":"https://clinicaltrials.gov/study/NCT02032823","refs":["olympia","olaparib","paper-olympia-6-year-update-ann-oncol-2026"]},{"item":"SCARLET (S2212) primary completion: shorter anthracycline-free chemo-immunotherapy vs the KEYNOTE-522 regimen (2,400 estimated participants)","expected":"2033-03-31","source":"https://clinicaltrials.gov/study/NCT05929768","refs":["scarlet-s2212","keynote-522","anthracycline","de-escalation"]},{"item":"OptimICE-pCR primary completion: adjuvant pembrolizumab vs observation after pathological complete response to chemotherapy plus pembrolizumab (1,295 estimated participants)","expected":"2033-05-31","source":"https://clinicaltrials.gov/study/NCT05812807","refs":["optimice-pcr","pembrolizumab","pcr","de-escalation"]},{"item":"A randomised trial of antibody-drug conjugate sequence (TROP2 conjugate then trastuzumab deruxtecan or the reverse, with or without chemotherapy between); none found on ClinicalTrials.gov on 24 September 2026","source":"https://europepmc.org/article/MED/41937088","refs":["adc-sequencing","idea-tnbc-adc-sequencing-trial"]},{"item":"A ctDNA-guided adjuvant trial in triple-negative breast cancer with early, tumour-informed sampling that reports after c-TRAK TN; the design lesson is recorded in the 2023 paper","source":"https://europepmc.org/article/MED/36423745","refs":["ctdna","mrd-testing","idea-tnbc-ctdna-guided-adjuvant-decisions"]}]},"route":"/roadmaps/tnbc-roadmap/","neighbours":{"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"},{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","route":"/roadmaps/tnbc-history/"},{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"pairing":[{"id":"adc-after-adc-caution","kind":"pairing","name":"Caution: TOP1 ADC immediately after TOP1 ADC","route":"/pairings/adc-after-adc-caution/"},{"id":"germline-to-parp","kind":"pairing","name":"Germline BRCA test → adjuvant PARP inhibitor","route":"/pairings/germline-to-parp/"},{"id":"platinum-plus-hrd","kind":"pairing","name":"Platinum chemotherapy in HRD tumours","route":"/pairings/platinum-plus-hrd/"}],"idea":[{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-tnbc-uk-trial-access-and-germline-testing-audit","kind":"idea","name":"A UK audit of trial access and germline testing uptake in triple-negative breast cancer","route":"/ideas/idea-tnbc-uk-trial-access-and-germline-testing-audit/"},{"id":"idea-tnbc-disparities-in-access-and-outcomes","kind":"idea","name":"Close the gap between who gets triple-negative breast cancer and who is in its trials","route":"/ideas/idea-tnbc-disparities-in-access-and-outcomes/"},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/"},{"id":"idea-tnbc-uk-ethnicity-stratified-outcome-reporting","kind":"idea","name":"Ethnicity-stratified outcome reporting for triple-negative breast cancer in NHS cancer statistics","route":"/ideas/idea-tnbc-uk-ethnicity-stratified-outcome-reporting/"},{"id":"idea-tnbc-de-escalation-for-exceptional-responders","kind":"idea","name":"Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease","route":"/ideas/idea-tnbc-de-escalation-for-exceptional-responders/"},{"id":"idea-tnbc-pd-l1-assay-harmonisation","kind":"idea","name":"Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance","route":"/ideas/idea-tnbc-pd-l1-assay-harmonisation/"},{"id":"idea-tnbc-her2-ultralow-testing-uptake","kind":"idea","name":"Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan","route":"/ideas/idea-tnbc-her2-ultralow-testing-uptake/"},{"id":"idea-tnbc-brain-metastasis-trials","kind":"idea","name":"Trials that include, and report, brain metastases in triple-negative breast cancer","route":"/ideas/idea-tnbc-brain-metastasis-trials/"}],"cancer":[{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"},{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"trop2-pet","kind":"technology","name":"TROP2 PET","route":"/technologies/trop2-pet/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","route":"/drugs/izalontamab-brengitecan/"},{"id":"nab-paclitaxel","kind":"drug","name":"Nab-paclitaxel","route":"/drugs/nab-paclitaxel/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"ventana-pd-l1-sp142","kind":"drug","name":"VENTANA PD-L1 (SP142) Assay","route":"/drugs/ventana-pd-l1-sp142/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"},{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"},{"id":"systimmune","kind":"company","name":"SystImmune / Sichuan Biokin","route":"/companies/systimmune/"}],"institution":[{"id":"asco","kind":"institution","name":"American Society of Clinical Oncology (ASCO)","route":"/institutions/asco/"},{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"},{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"},{"id":"esmo","kind":"institution","name":"European Society for Medical Oncology (ESMO)","route":"/institutions/esmo/"},{"id":"gbg","kind":"institution","name":"German Breast Group (GBG)","route":"/institutions/gbg/"},{"id":"mayo-clinic","kind":"institution","name":"Mayo Clinic","route":"/institutions/mayo-clinic/"},{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/"},{"id":"royal-marsden","kind":"institution","name":"The Royal Marsden","route":"/institutions/royal-marsden/"},{"id":"unc-lineberger","kind":"institution","name":"UNC Lineberger Comprehensive Cancer Center","route":"/institutions/unc-lineberger/"}],"pathway":[{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"term":[{"id":"adc-sequencing","kind":"term","name":"ADC 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(IHC)","route":"/terms/ihc/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pam50","kind":"term","name":"PAM50 / intrinsic subtypes","route":"/terms/pam50/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"},{"id":"taxane","kind":"term","name":"Taxanes (paclitaxel, docetaxel, nab-paclitaxel)","route":"/terms/taxane/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"biomarker":[{"id":"her2-ultralow","kind":"biomarker","name":"HER2-ultralow (IHC 0 with 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