Abstract PS09-06: Tumor infiltrating lymphocytes as a predictor of pathologic complete response to neoadjuvant therapy in HER2 positive breast cancer
Authors: Alberto Monroy Chargoy, Haydee Cristina Verduzco-Aguirre, Javier Monroy Chargoy, Jose Rodrigo Espinosa-Fernandez, Jesus Antonio Martinez Ojeda, Paula Cabrera-Galeana
Journal: Cancer Research (2024)

Abstract Background The presence of tumor infiltrating lymphocytes (TILs) has shown positive prognostic relevance for certain subtypes of breast cancer, although its value as a predictive biomarker is still uncertain. The purpose of this study was to study the association between TILs expression with the pathologic complete response (pCR) following neoadjuvant therapy in Mexican patients with HER2+ breast cancer. Methods Retrospective cohort of patients with stage I-III HER2+ breast cancer who received neoadjuvant therapy between 2017 and 2020 at Instituto Nacional de Cancerología (INCan). We collected demographic and clinico-pathological characteristics. Stage was assigned using AJCC 7th criteria; hormone receptor (HR) and HER2 status were determined according to ASCO-CAP guidelines. Quantification of TILs was made by microscopy and stained with hematoxylin-eosin. TIL levels were defined as low (1-10%) intermediate (11-40%) and high ( &amp;gt;40%). Complete pathologic response was defined as the absence of invasive disease in breast and axilla (ypT0/is N0). pCR rates were compared using X2 and Fisher's exact tests according to demographic and clinicopathologic characteristics. Univariate logistic regression analysis was performed to estimate the probability of pCR according to relevant characteristics. Those parameters with p ≤0.10 on univariate analysis were included in a multivariate logistic regression model. A p&amp;lt; 0.05 was considered as statistically significant. Results We included 164 patients (mean age 51.0 years, SD 11.4). 86 patients (54.1%) were postmenopausal, 75 patients (47.2%) had T3-T4 tumors, 129 patients (81.1%) had positive lymph nodes, 133 patients (83.6%) presented Ki67 ≥30%, 59 patients (37.1%) had negative hormone receptors, 136 patients (85.5%) were treated with anthracyclines and 20 patients (12.6%) received dual anti-HER2 therapy with trastuzumab/pertuzumab. TIL expression was low in 84 patients (52.8%), intermediate in 47 (29.6%), and high in 28 patients (17.6%). The pathologic complete response (pCR) rate in the overall population was 50.9%. pCR rates according to the demographic and clinico-pathological features are listed in Table 1. In patients with intermediate-high TILs, pCR rates were 73.1% with trastuzumab, and 75.0% with dual HER2 blockade (p=0.91). Among patients with low TILs, pCR rates were 23.6% and 75.0%, respectively (p &amp;lt; 0.001). On univariate analysis, intermediate TILs (OR 3.59; 95% C.I 1.70-7.59; p= &amp;lt; 0.001), high TILs (OR 29.00; 95% C.I 6.40-131.37; p= &amp;lt; 0.001), Ki67 ≥30% (OR 2.73, 95% C.I 1.11-6.73; p=0.02), and dual anti-HER2 therapy (OR 3.31; 95% C.I 1.14-9.63 p= 0.021) were associated with a higher probability of pCR. T3/T4 tumor size (OR 0.43; 95% C.I 0.22-0.81; p = 0.009) was associated with a lower probability of pCR. Positive lymph nodes, HR status , and use of anthracyclines were not significantly associated. On multivariate analysis, intermediate TILs (OR 3.28; 95% C.I 1.46-7.32 p=.004), high TILs (OR 32.37; 95% C.I 6.84-153.04 p= &amp;lt; 0.001), and dual anti-HER2 therapy (OR 6.58; 95% CI 2.01-21.47 p= .002) remained significantly associated with pCR. Conclusions Intermediate/high TIL expression was significantly associated with pCR. Our results suggest that TIL expression could help select patients with locally advanced HER2+ breast cancer for treatment intensification with dual HER2 blockade in resource-limited settings. However, these findings require confirmation in larger, prospective studies before implementation into routine practice. TABLE 1. Pathologic complete response (pCR) rates according to demographic and clinical pathological features (n=164). Citation Format: Alberto Monroy Chargoy, Haydee Cristina Verduzco-Aguirre, Javier Monroy Chargoy, Jose Rodrigo Espinosa-Fernandez, Jesus Antonio Martinez Ojeda, Paula Cabrera-Galeana. Tumor infiltrating lymphocytes as a predictor of pathologic complete response to neoadjuvant therapy in HER2 positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS09-06.