Background: Scientific evidence strongly indicates that locoregional control in early-stage breast cancer (BC) by lumpectomy with radiation therapy or by mastectomy yields similar disease-free survival (DFS) and overall survival (OS). A recent retrospective review of a Danish prospective database demonstrated strong favorable interaction between radiotherapy (RT) and all BC subtypes that contain high amount of tumor infiltrating lymphocytes (TILs).

Objective: We aim to compare DFS and OS in patients with early-stage HER2-positive BC, whose tumors demonstrate high involvement by TILs after locoregional treatment by either mastectomy or lumpectomy and whole breast radiotherapy.

Methods: We retrospectively reviewed the charts and histopathology slides of patients with HER2-positive BC with clinical stage T1-T2 N0, who were treated in our center between January 2009 and December 2018. Locoregional management included either mastectomy (no radiation group) or lumpectomy with whole breast irradiation (radiation group). Stromal TILs were estimated using hematoxylin-eosin staining, according to the recommendations of the TILs working group 2014. This was performed by 3 independent pathologists who were blinded to the clinical course of the patients. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used to estimate correlations between TILs and clinical outcomes.

Results: A total of 110 charts were reviewed and 99 were included in the final analysis. Patients were dichotomized into groups of “low-TILs” and “high-TILs” using a 40% cut off. Approximately 25% of patients (26/99) were “high-TILs” and around 50% of the “high-TILs” and “low-TILs” patients received RT. In all groups, around 90% of patients received chemotherapy and anti-HER2 therapy. All hormone receptor-positive patients received adjuvant endocrine therapy. While RT did not result in significant DFS or OS advantage in the low-TILs group, patients with high-TILs had significant improvement of DFS and OS with the addition of RT. Table 1 depict the 5-year DFS and 5-year OS in "high-TILs" and "low-TILs" groups in relation to RT, respectively.

Conclusion: In this retrospective analysis, our findings indicate that in high-TILs early-stage HER2-positive BC, RT was associated with significant improvement of 5-year DFS and OS. The exact mechanism is not well understood. However, this observation is important and warrants confirmation in prospective clinical trials.

5-year DFS5-year OS
High TILsLow TILsHigh TILsLow TILs
RT group 100% 90% 100% 83% 
No RT group 65% 90% 72% 93% 
p-value 0.027 0.96 0.025 0.184 
5-year DFS5-year OS
High TILsLow TILsHigh TILsLow TILs
RT group 100% 90% 100% 83% 
No RT group 65% 90% 72% 93% 
p-value 0.027 0.96 0.025 0.184 

Citation Format: Jason A Mouabbi, Momal Chand, Ramen Sakhi, Ishaq A Asghar, Daniel Ockner, Tarik Hadid, Carrie L Dul, Mothaffar F Rimawi, Amer Aref. Radiation therapy improves survival in early-stage HER2-positive breast cancer with high-level of tumor infiltrating lymphocytes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-01.