Bold takeaway: Baseline stromal tumor–infiltrating lymphocytes (sTILs) strongly predict how likely patients with stage II/III HER2-positive breast cancer are to achieve a pathologic complete response (pCR) after neoadjuvant THP therapy. And this is the part some readers may find provocative: the strength and consistency of that link vary across subgroups, raising important questions about how we tailor preoperative treatment.
A secondary analysis of the EA1181 CompassHER2-pCR trial (phase 2 ECOG-ACRIN Cancer Research Group) examined whether the baseline percentage of sTILs could forecast pCR in patients receiving neoadjuvant therapy. The trial enrolled individuals with stage II/III HER2-positive breast cancer who were treated with four cycles of trastuzumab (H) and pertuzumab (P) plus 12 weeks of taxane chemotherapy (paclitaxel or docetaxel), followed by surgery. Baseline sTIL density was measured on full-face hematoxylin and eosin–stained tumor biopsy sections, focusing on stromal TILs. The analysis looked at sTILs both as a continuous variable (per 10% increase) and categorically using prespecified cutoffs: <10% vs ≥10%, with an exploratory cutoff of <30% vs ≥30%.
Among 2,141 eligible EA1181 participants, tumor slides suitable for sTIL assessment existed for 1,328 individuals (62%), and this subcohort reflected the broader study population. The overall pCR rate across evaluable patients was 44.5%. Notably, pCR rates differed by hormone receptor status: 64% for HER2-positive/ER-negative disease versus 33% for HER2-positive/ER-positive disease.
sTIL levels fell into two broad realities: roughly half of tumors had low sTILs (<10%), while a little over half had 10% or more sTILs (47% and 53%, respectively).
In both univariable and multivariable analyses, each 10% rise in baseline sTILs (analyzed continuously) correlated with higher odds of achieving pCR across the entire cohort and within both ER-positive and ER-negative subgroups (P<0.001 in all cases). Specifically, in multivariable modeling, every 10% increase in sTILs translated to a 26% higher chance of pCR (odds ratio [OR] 1.26; 95% CI, 1.13–1.41).
When treated as a categorical variable, tumors with ≥10% sTILs were more likely to reach pCR than those with <10% sTILs in the overall group (OR 1.93; 95% CI, 1.55–2.41) and in the ER-positive subset (OR 1.80; 95% CI, 1.35–2.41). The categorical association did not reach statistical significance in the ER-negative subset (OR 1.32; 95% CI, 0.90–1.94).
Exploratory analyses using a higher cutoff of ≥30% sTILs showed a similar association with pCR in univariable testing for both hormone receptor groups. After adjustment, however, the ≥30% cutoff remained a significant independent predictor of pCR only in HER2-positive/ER-positive disease.
Overall, these findings reinforce the idea that immune activity within tumors—reflected by sTILs—plays a meaningful role in the response of HER2-positive breast cancer to THP therapy. They also suggest baseline sTILs could become a useful predictive biomarker to guide preoperative trial design and treatment optimization in future studies, helping clinicians tailor neoadjuvant strategies to individual tumor immune landscapes.
Do these results imply we should routinely measure baseline sTILs to decide who gets THP therapy preoperatively, or should we reserve their use for refining trial designs? Share your perspective on the balance between biomarker-guided personalization and broader treatment accessibility in the comments.
