Abstract P3-19-04: Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients
Authors: Currey Adam , Jorns Julie M , Desai Nina , Kelly Tracy R , Bovi Joseph , Kong Amanda L , Wadhwa Anubha , Paulson Eric , Bergom Carmen 
Published: March 2022

Abstract
Purpose/Objectives: Local immune activity as measured by tumor infiltrating lymphocytes (TILs) has been correlated with improved outcomes in triple negative breast cancer (TNBC) and HER2+ disease. Furthermore, increased TILs after pre-operative systemic therapy for TNBC are also correlated with improved outcomes. However, the role of TILs in predicting outcomes in ER/PR+ breast cancer is less well-established. Radiation therapy (RT) can enhance immune cell infiltration in various tumors. However, breast cancer RT is typically given post-operatively, limiting the ability to determine whether RT enhances the %TILs in breast tumors. Here we report %TILs and tumor responses after pre-operative accelerated partial breast irradiation (APBI) as part of a clinical trial to determine whether RT enhances %TILs and whether this correlates with RT response. Materials/Methods: A breast pathologist assessed blindly the % stromal TILs and % tumor cellularity in biopsy and post-RT surgical specimens for patients treated on an in-house pre-operative APBI trial in patients with ER/PR+ breast cancer (NCT02728076). Patients received APBI to 30 Gy in 5 fractions on non-consecutive days, followed by surgery after no less than 5 weeks. Correlation between %TILs and pathologic response was assessed. Results: Thirty-five patients were enrolled and completed treatment. Median age was 65 (50-80). All patients were clinically node-negative and ER/PR+; one was HER2+. Median MRI tumor size was 0.9 cm (0.4-2.1 cm); 54% were grade 2 and 46% grade 1. 23/35 patients had 21- or 70-gene recurrence scores (RS), with 1 high RS; 2 patients received adjuvant chemotherapy and 33/35 received endocrine therapy after surgery. Most patients demonstrated robust tumor responses to RT, with 16/35 (46%) having &lt5% cellularity after RT. With a median cellularity at diagnosis of 40%, 27/35 (77%) had a &gt;20% decrease in cellularity, with only 3 patients having no decrease (range 0-59%). All tumors had low levels of TILs (median 5%, range 1-20%). There was minimal change in %TILs from biopsy to surgery, with 10/35 (28%) patients having increase of TILs &gt4%, 2/35 with an increase of 10%, 2/35 having a decrease of 10% and the remainder with no %TIL increase. There were no correlations between %TILs (at diagnosis or post-RT) and tumor response to RT or RS. Conclusions: Pre-operative APBI in ER/PR+ breast cancers did not significantly increase the %TILs after 5 weeks, despite leading to significant tumor responses as measured by % cellularity. Low %TILs were seen, with no more than a 10% TIL increase after RT. These findings suggest this RT dose and fractionation schedule causes only mild immune changes, as measured by TILs, in this mostly favorable cohort of ER/PR+ cancers. Alternatively, the timing of surgery may have missed maximum TIL levels. Further characterization of TILs along with further studies in similar cohorts and in other breast cancer subtypes are warranted and will be performed to examine the role of pre-operative RT on breast cancer immune responses.
Citation Format: Adam Currey, Julie M Jorns, Nina Desai, Tracy R Kelly, Joseph Bovi, Amanda L Kong, Anubha Wadhwa, Eric Paulson, Carmen Bergom. Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-04.