Baseline Stromal Tumor-Infiltrating Lymphocytes as Predictors of Pathologic Response in HER2-Positive Breast Cancer
Key Clinical Takeaways
- Design/Population: This secondary analysis evaluated sTIL density in 1328 patients with clinical stage II/III HER2-positive breast cancer treated in CompassHER2 with preoperative trastuzumab plus pertuzumab and taxane-based therapy. sTILs were quantified from diagnostic biopsies and assessed continuously and categorically, including exploratory thresholds.
- Key Outcomes: Higher sTIL levels were consistently associated with increased likelihood of pCR across HER2-positive/ER-positive and HER2-positive/ER-negative subgroups. The exploratory ≥30% cutoff predicted pCR in univariable analyses across subtypes, though significance persisted in multivariable models only for HER2-positive /ER-positive disease.
- Clinical Relevance: Findings reinforce the role of the immune microenvironment in predicting response to preoperative trastuzumab plus pertuzumab and taxane-based therapy in HER2-positive breast cancer. Baseline sTILs may serve as a useful biomarker to guide preoperative therapy selection and inform trial designs aiming to optimize HER2-targeted regimens.
According to secondary analysis results from the CompassHER2 pCR trial, baseline stromal tumor-infiltrating lymphocytes (sTILs) were associated with pathologic complete response (pCR) following preoperative trastuzumab plus pertuzumab and taxane-based therapy among patients with HER2-positive breast cancer.
These findings were presented by Sunil Badve, MD, Winship Cancer Institute, Atlanta, Georgia, at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.
In this study, researchers collected data from 1328 patients who underwent 4 cycles of trastuzumab and pertuzumab plus 12 cycles of paclitaxel or docetaxel prior to surgical resection. sTIL density was measured on hematoxylin and eosin-stained biopsy sections and analyzed both continuously (per 10% increment) and categorically (<10%; 10 to 60%; >60%). An exploratory 30% cutoff commonly used in triple-negative breast cancer was also assessed. Univariable and multivariable Cox proportional hazards models examined associations between sTILs and pCR and clinicopathologic correlations were evaluated using Fisher exact tests.
At analysis, the pCR rate was 44.5% overall, 64% in patients with HER2-positive or ER-negative disease, and 33% in patients with HER-positive or ER-positive disease. sTIL distribution included 47% with <10% sTILs and 53% with ≥10% sTILs. Increasing sTILs as a continuous variable was significantly associated with higher pCR rates across both HER2-positive or ER-negative and HER-positive or ER-positive subsets (P <.001). Categorical analysis (<10% vs ≥10%) also demonstrated significant associations with pCR in the overall population and in patients with HER-positive or ER-positive disease.
Using the exploratory <30% vs ≥30% cutoff, sTILs ≥30% were associated with increased pCR rates in univariable analyses in patients with both HER2-positive or ER-positive (P <.001) and HER2-positive or ER-negative disease (P = .045). In multivariable analysis, sTILs ≥30% remained significantly associated with pCR only in HER2-positive or ER-positive tumors.
“sTILs were associated with pCR after [trastuzumab plus pertuzumab and taxane-based therapy], further supporting the important role of immune mechanisms in [HER2-positive] breast cancer, and highlighting a potentially robust predictive tool to assess pathologic response,” concluded Dr Badve et al. “Baseline sTILs could potentially inform the preoperative design of future trials of therapy optimalization.”
Source:
Badve S, Zhao F, Tung N, et al. Tumor infiltrating lymphocytes (TILs) and pathologic complete response (pCR) in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): secondary results from the ECOG-ACRIN-1181/CompassHER2 pCR trial. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract GS1-04
