Kefah Mokbel, Chair of Breast Cancer Surgery at London Breast Institute and Honorary Professor of Medicine at Cardiff University School of Medicine, shared a post on LinkedIn:
“Why do only half of patients with triple-negative breast cancer respond to chemotherapy?
A landmark study published in Nature offers important new insights into this question.
The authors performed single-cell and spatial transcriptomic profiling of 427,857 cells from 101 treatment-naïve TNBC patients – one of the largest datasets of its kind – and identified a complex cellular ecosystem associated with chemotherapy response.
Key findings:
- Four cancer-cell archetypes (ARC1-4) identified purely from malignant cells – avoiding the confounding effects of the tumour microenvironment inherent to prior bulk-tissue subtyping.
- ARC3 (interferon-responsive) was strongly associated with pathological complete response (pCR), whereas ARC2 (basal-like) predicted residual disease.
- 13 intratumoral metaprograms defined, including interferon signalling (M5), HLA class II expression (M6), and S-phase cell cycling (M7), all enriched in pCR tumours.
- Macrophage subtypes emerged as stronger correlates of chemotherapy response than T-cell states in this dataset, highlighting an underappreciated component of TNBC immune biology.
- Eight cellular ‘ecotypes’ mapped the spatial architecture of the tumour microenvironment, linking cellular co-occurrence patterns to treatment outcomes.
- A 13-gene panel derived from single-cell data predicted neoadjuvant chemotherapy response (AUC 0.84) and overall survival across multiple independent TNBC cohorts.
This study significantly advances our understanding of TNBC biology and supports further exploration of macrophage-targeted therapies, predictive biomarkers, and more personalised treatment strategies.
Perhaps the broader lesson is this: in TNBC, the ecosystem matters as much as the cancer cell itself.”
Title: Ecotypes of triple-negative breast cancer in response to chemotherapy
Authors: Yun Yan, Yiyun Lin, Tapsi Kumar, Shanshan Bai, Aatish Thennavan, Jianzhuo Li, Emi Sei, Tuan Tran, Min Hu, Mitchell Rao, Chenling Tang, Siyuan He, Anna Casasent, Elizabeth Ravenberg, Gaiane Margishvili Rauch, Alyson R. Clayborn, Debu Tripathy, Alastair Thompson, Bora Lim, Lei Huo, Stacy Moulder, Clinton Yam, Nicholas Navin
Read The Full Article
Other articles about Breast Cancer on OncoDaily.