Abstract P4-10-18: Changes in tumour infiltrating lymphocytes during neoadjuvant endocrine therapy and possible clinical implications for guiding therapy
Authors: Skriver Signe Korsgaard , Jensen Maj-Britt , Knoop Ann Soegaard , Ejlertsen Bent , Laenkholm Anne-Vibeke 
Published: March 2020

Abstract
Background: Stromal Tumour Infiltrating Lymphocytes (sTILs) has been established as a predictive biomarker for response to neoadjuvant chemotherapy irrespective of subtype. While increased sTIL levels is associated with prolonged survival among patients with triple-negative and HER2 positive breast cancer increased sTILs has in Estrogen Receptor positive (ER+) breast cancer been suggested to be an adverse prognostic factor. It has been hypothesised that differences in the cellular composition of immune cells may explain the dissimilarity in prognostic impact according to breast cancer subtype.
Here, we report data from a neoadjuvant phase II study, treating postmenopausal patients with primary ER+, HER2 negative, operable breast cancer with letrozole for four months by the Danish Breast Cancer Group (DBCG). We analysed the association of sTILs, and changes in sTILs during neoadjuvant endocrine treatment (NET), with pathological response and correlation with other clinicopathological variables such as Ki67, as potential biomarkers for risk-stratification of patients following NET.
Method: 113 postmenopausal patients with ER+, HER2 negative breast cancer were treated with NET for four months. Endpoint was pathological response assessed by a modified Miller Payne scale and the Residual Cancer Burden (RCB) score. Pretherapeutic core biopsies and post therapeutic surgical specimens were assessed centrally for the percentage of sTILs on HE sections according to the International TILs working group guidelines. sTILs association to pathological response were assessed with univariate logistic regression. Odds Ratio (OR) was estimated with a 95 % confidence interval. Correlation of sTILs and Ki67 were tested with Pearson´s correlation coefficient. Changes in sTILs with a paired t-test. Level of significance was set to 5 %.
Results: sTILs concentration increased with mean 6.8 % (p &lt;.0001) during treatment in the assessable patients (range -39 % - 60 %). Forty-four percent had no pathological response as assessed by the modified Miller Payne scale and 11 % had RCB-Class III after NET. Increase in sTILs was significantly associated with poorer pathological response with OR=1.38 (95 % CI: 1.05 - 1.82; p = 0.03) per 10 % increase for no pathological response, and correspondingly OR=1.78 (95 % CI: 1.27 - 2.50; p &lt;.0001) for higher level RCB-class per 10 % increase.
The correlation between pre-therapeutic sTILs and Ki67 was moderate (Pearson 0.4; p = 0.0004), however the association grew stronger post treatment (Pearson 0.5; p &lt;.0001).
Conclusion: Increased sTILs activity during NET was associated with poor treatment response. An increase in sTILs during NET could be considered indictive for potential immunogenic tumours, suggesting that patients with increasing sTIL in residual disease after NET might derive benefit from the addition of immunotherapy.
We found a significant correlation between sTILs and Ki67 levels. Ki67 has been established as a window of opportunity biomarker for antiproliferative response. Combining biomarkers of antiproliferative response such as Ki67 with biomarkers of immunogenetic significance might be important to determine optimal combination of adjuvant therapy. A window of opportunity study with an aromatase inhibitor could show if it is feasible to detect a rise in sTILs early enough to guide adjuvant treatment in the perioperative setting.
Citation Format: Signe Korsgaard Skriver, Maj-Britt Jensen, Ann Soegaard Knoop, Bent Ejlertsen, Anne-Vibeke Laenkholm. Changes in tumour infiltrating lymphocytes during neoadjuvant endocrine therapy and possible clinical implications for guiding therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-18.