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William J. Gradishar, MD, FACP, FASCO


ASCO 2023: Predicting Response to Neoadjuvant Chemoimmunotherapy for Triple-Negative Breast Cancer

By: Julia Fiederlein Cipriano
Posted: Friday, June 23, 2023

In patients with triple-negative breast cancer who underwent chemoimmunotherapy, Shane R. Stecklein, MD, PhD, of the University of Kansas Medical Center, Kansas City, and colleagues found that the degree of stromal tumor–infiltrating lymphocyte enrichment and a proliferation signature offered complementary information in predicting pathologic complete responses. The results of this biomarker analysis of the phase II NeoPACT trial were presented during the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting (Abstract 507).

The investigators focused on 110 patients with available whole-exome RNA sequencing data who underwent neoadjuvant chemoimmunotherapy with carboplatin plus docetaxel and pembrolizumab. They were grouped based on the degree of stromal tumor–infiltrating lymphocyte enrichment (immune-high: ≥ 20% cells, 51%; immune-low: < 20% cells, 49%). The samples were categorized as proliferation signature–high (≥ median) or –low (< median).

More than half of patients (57%) achieved a pathologic complete response. Both the degree of enrichment (odds ratio [OR] = 1.022, P = .001) and proliferation signature (OR = 2.682, P = .01) as continuous variables were found to be predictive of pathologic complete response. In the immune-low group, the proliferation signature appeared to be significantly associated with pathologic complete response, both as a continuous score (AUC = 0.74) and when assessed as high/low categories (57% vs. 29%, OR = 3.18, P = .045). However, this trend did not seem to hold true in the immune-high group (continuous score: AUC = 0.56; high/low: 78% vs. 67%, OR = 1.79, P = .34). Based on a multivariate analysis, both the degree of enrichment (OR = 1.02, P = .004) and proliferation signature (OR = 3.13, P = .004) were independent predictors of pathologic complete response.

“We hypothesize that the therapeutic response in [immune]-high tumors is dominated by lymphocyte-dependent cytotoxic mechanisms,” the investigators concluded. “In [immune]-low tumors, the response may be dominated by proliferation-dependent responses.”

Disclosure: Dr. Stecklein reported no conflicts of interest. For full disclosures of the other study authors, visit

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