{"entity":{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","aka":[],"tldr":"How triple-negative breast cancer went from the subtype with no targeted therapy to one with immunotherapy, PARP inhibitors, three ADCs, and a positive bispecific ADC in six years.","summary":"The TNBC roadmap begins in the chemotherapy-only years, when the basal-like subtype was defined, anthracycline-taxane regimens with carboplatin were all that existed and EGFR, VEGF and PARP inhibitor trials failed. Immunotherapy and PARP inhibitors arrived with IMpassion130, OlympiAD, EMBRACA, KEYNOTE-355 and ASCENT, then KEYNOTE-522 and OlympiA transformed the curative setting and DESTINY-Breast04 opened T-DXd to HER2-low disease. Now ADCs move to first line through ASCENT-03, ASCENT-04 and TROPION-Breast02, with OptimICE-pCR, SCARLET, ctDNA-guided escalation and post-neoadjuvant ADCs as the emerging steps. The turning point was recognising that TNBC could be targeted without an oncogenic driver; the route links the TNBC record and the ADC and immunotherapy sections.","asOf":"2026-09-04","links":[{"label":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2112651"},{"label":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"}],"tags":[],"related":["tnbc-roadmap"],"cancers":["tnbc"],"sections":["adcs","immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"2000-2015","title":"Chemotherapy only","description":"Basal-like subtype defined (2000); TNBC named by exclusion (2007). Anthracycline-taxane chemotherapy; carboplatin added (2014). Median metastatic OS was about 13-18 months, and EGFR, VEGF, and PARP inhibitor (iniparib) trials failed repeatedly.","refs":["carboplatin","platinum"],"status":"historic"},{"era":"2018-2020","title":"Immunotherapy and PARP arrive","description":"The pivotal trials are IMpassion130 (atezolizumab, later withdrawn), OlympiAD/EMBRACA (PARP inhibitors in gBRCA), KEYNOTE-355 (pembrolizumab CPS ≥10 first line), ASCENT (sacituzumab govitecan).","refs":["impassion130","olaparib","talazoparib","keynote-355","ascent"],"status":"historic"},{"era":"2021-2022","title":"Curative setting transformed","description":"KEYNOTE-522 makes chemo-immunotherapy the standard for stage II-III; OlympiA adds adjuvant olaparib for gBRCA. DESTINY-Breast04 makes HER2-low TNBC eligible for T-DXd.","refs":["keynote-522","olympia","destiny-breast04"],"status":"historic"},{"era":"2024-2026","title":"ADCs move to first line; bispecific ADC succeeds","description":"KEYNOTE-522 OS benefit confirmed. ASCENT-03/04 and TROPION-Breast02 read out positive, bringing first-line approvals for sacituzumab govitecan and Dato-DXd (2026). Iza-bren posts a positive phase 3 (2026). TIL-based de-escalation in stage I gains evidence.","refs":["ascent-03","ascent-04","tropion-breast02","bl-b01d1-307","tils"],"status":"current"},{"era":"2026-2029","title":"Next: residual disease, de-escalation, selection","description":"OptimICE-pCR (omit adjuvant pembrolizumab after pCR), SCARLET (drop anthracycline), ctDNA-guided escalation for RCB II-III, ADCs in the post-neoadjuvant setting, sac-TMT and TROPION-Breast05 first-line readouts, IZABRIGHT-Breast01, TROP2 PET.","refs":["optimice-pcr","scarlet-s2212","tropion-breast05","izabright-breast01","sacituzumab-tirumotecan","trop2-pet","mrd-testing"],"status":"emerging"},{"era":"2029+","title":"Speculative: cure for most, control for the rest","description":"Neoadjuvant ADC + IO replacing anthracyclines; personalised vaccines in the adjuvant setting for high-risk residual disease; payload-switching ADC algorithms guided by PET and ctDNA; mesenchymal-subtype-specific therapy; brain-penetrant ADCs.","refs":["neoantigen-mrna-vaccine","dual-payload-adc","emt","idea-post-neoadjuvant-adc"],"status":"speculative"}],"watch":[]},"route":"/roadmaps/tnbc-history/","neighbours":{"roadmap":[{"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","route":"/roadmaps/tnbc-roadmap/"}],"cancer":[{"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":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"}],"technology":[{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","route":"/technologies/dual-payload-adc/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"id":"trop2-pet","kind":"technology","name":"TROP2 PET","route":"/technologies/trop2-pet/"}],"trial":[{"id":"ascent","kind":"trial","name":"ASCENT","route":"/trials/ascent/"},{"id":"ascent-03","kind":"trial","name":"ASCENT-03","route":"/trials/ascent-03/"},{"id":"ascent-04","kind":"trial","name":"ASCENT-04 / KEYNOTE-D19","route":"/trials/ascent-04/"},{"id":"bl-b01d1-307","kind":"trial","name":"BL-B01D1-307","route":"/trials/bl-b01d1-307/"},{"id":"destiny-breast04","kind":"trial","name":"DESTINY-Breast04","route":"/trials/destiny-breast04/"},{"id":"impassion130","kind":"trial","name":"IMpassion130","route":"/trials/impassion130/"},{"id":"izabright-breast01","kind":"trial","name":"IZABRIGHT-Breast01","route":"/trials/izabright-breast01/"},{"id":"keynote-355","kind":"trial","name":"KEYNOTE-355","route":"/trials/keynote-355/"},{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"},{"id":"olympia","kind":"trial","name":"OlympiA","route":"/trials/olympia/"},{"id":"optimice-pcr","kind":"trial","name":"OptimICE-pCR (A012103)","route":"/trials/optimice-pcr/"},{"id":"scarlet-s2212","kind":"trial","name":"SCARLET (SWOG S2212)","route":"/trials/scarlet-s2212/"},{"id":"tropion-breast02","kind":"trial","name":"TROPION-Breast02","route":"/trials/tropion-breast02/"},{"id":"tropion-breast05","kind":"trial","name":"TROPION-Breast05","route":"/trials/tropion-breast05/"}],"term":[{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"pathway":[{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"}],"idea":[{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/"}]}}