Computationally Derived Spatial Immune Signature Identifies Trastuzumab Responders in HER2+ Breast Cancer: NSABP B41 Clinical Trial Validation.
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OpenAlex 토픽 ·
HER2/EGFR in Cancer Research
Cancer Immunotherapy and Biomarkers
Monoclonal and Polyclonal Antibodies Research
[PURPOSE] Trastuzumab-based chemotherapy has improved outcomes in human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but treatment benefit varies among patients.
- 표본수 (n) 250
- p-value p = 0.006
- p-value p = 0.024
- 95% CI 0.01-0.77
- HR 0.09
APA
Satvika Bharadwaj, Germán Corredor, et al. (2026). Computationally Derived Spatial Immune Signature Identifies Trastuzumab Responders in HER2+ Breast Cancer: NSABP B41 Clinical Trial Validation.. Clinical cancer research : an official journal of the American Association for Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-4185
MLA
Satvika Bharadwaj, et al.. "Computationally Derived Spatial Immune Signature Identifies Trastuzumab Responders in HER2+ Breast Cancer: NSABP B41 Clinical Trial Validation.." Clinical cancer research : an official journal of the American Association for Cancer Research, 2026.
PMID
41915435 ↗
Abstract 한글 요약
[PURPOSE] Trastuzumab-based chemotherapy has improved outcomes in human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but treatment benefit varies among patients. Predictive signatures are needed to identify patients most likely to respond to these therapies.
[EXPERIMENTAL DESIGN] We developed DeSTIL (Density and Spatial architecture of Tumor-Infiltrating Lymphocytes), a computational signature derived from hematoxylin and eosin slides. The signature captures spatial organization of immune cells and interactions with non-immune cells. DeSTIL was trained on HER2+ breast cancer slides from The Cancer Genome Atlas (n = 250) and validated in phase III NSABP B-41 randomized clinical trial (n=221), which compared chemotherapy plus trastuzumab, lapatinib, or combination. The DeSTIL scores were dichotomized into positive and negative groups, and event-free survival (EFS) was assessed using Cox proportional hazards with interaction terms.
[RESULTS] In NSABP B41, DeSTIL-positive patients (n=61) showed significantly improved EFS with trastuzumab compared to the combination arm (HR = 0.09, 95% CI 0.01-0.77; p = 0.006) and a significant signature-treatment interaction (p = 0.024). No EFS difference was observed in DeSTIL-negative patients (n=160). Gene expression analysis supported the image-derived signature stratifying DeSTIL-positive and DeSTIL-negative tumors. In an exploratory pCR analysis, a classifier trained on University Hospitals Cleveland slides achieved an AUC of 0.70 in the training cohort and 0.63 in the trastuzumab arm of the NSABP B-41 validation cohort.
[CONCLUSIONS] DeSTIL identifies a subset of HER2+ patients who derive greater benefit from trastuzumab. These findings support the potential of computationally derived immune architecture to inform selection of standard HER2-targeted therapies.
[EXPERIMENTAL DESIGN] We developed DeSTIL (Density and Spatial architecture of Tumor-Infiltrating Lymphocytes), a computational signature derived from hematoxylin and eosin slides. The signature captures spatial organization of immune cells and interactions with non-immune cells. DeSTIL was trained on HER2+ breast cancer slides from The Cancer Genome Atlas (n = 250) and validated in phase III NSABP B-41 randomized clinical trial (n=221), which compared chemotherapy plus trastuzumab, lapatinib, or combination. The DeSTIL scores were dichotomized into positive and negative groups, and event-free survival (EFS) was assessed using Cox proportional hazards with interaction terms.
[RESULTS] In NSABP B41, DeSTIL-positive patients (n=61) showed significantly improved EFS with trastuzumab compared to the combination arm (HR = 0.09, 95% CI 0.01-0.77; p = 0.006) and a significant signature-treatment interaction (p = 0.024). No EFS difference was observed in DeSTIL-negative patients (n=160). Gene expression analysis supported the image-derived signature stratifying DeSTIL-positive and DeSTIL-negative tumors. In an exploratory pCR analysis, a classifier trained on University Hospitals Cleveland slides achieved an AUC of 0.70 in the training cohort and 0.63 in the trastuzumab arm of the NSABP B-41 validation cohort.
[CONCLUSIONS] DeSTIL identifies a subset of HER2+ patients who derive greater benefit from trastuzumab. These findings support the potential of computationally derived immune architecture to inform selection of standard HER2-targeted therapies.