# TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line

Source: https://onco.cc/roadmaps/tnbc-history/  
OnCo record `tnbc-history` (Roadmap). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-04

## Sources

- KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer (New England Journal of Medicine 2022): https://doi.org/10.1056/NEJMoa2112651
- ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021): https://doi.org/10.1056/NEJMoa2028485

## Connected records

- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Olaparib](https://onco.cc/drugs/olaparib/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- technologies: [Dual-payload ADC](https://onco.cc/technologies/dual-payload-adc/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [Platinum agents](https://onco.cc/technologies/platinum/), [TROP2 PET](https://onco.cc/technologies/trop2-pet/)
- trials: [ASCENT](https://onco.cc/trials/ascent/), [ASCENT-03](https://onco.cc/trials/ascent-03/), [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/), [BL-B01D1-307](https://onco.cc/trials/bl-b01d1-307/), [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/), [IMpassion130](https://onco.cc/trials/impassion130/), [IZABRIGHT-Breast01](https://onco.cc/trials/izabright-breast01/), [KEYNOTE-355](https://onco.cc/trials/keynote-355/), [KEYNOTE-522](https://onco.cc/trials/keynote-522/), [OlympiA](https://onco.cc/trials/olympia/), [OptimICE-pCR (A012103)](https://onco.cc/trials/optimice-pcr/), [SCARLET (SWOG S2212)](https://onco.cc/trials/scarlet-s2212/), [TROPION-Breast02](https://onco.cc/trials/tropion-breast02/), [TROPION-Breast05](https://onco.cc/trials/tropion-breast05/)
- terms: [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- pathways: [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/)
- ideas: [ADC for residual disease after KEYNOTE-522](https://onco.cc/ideas/idea-post-neoadjuvant-adc/)

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