Impact of prior systemic therapy on lymphocytic infiltration in surgically resected breast cancer brain metastases Journal Article


Authors: Chew Minmin, S.; Bacotti, A.; Chen, Y.; Anders, C.; Sambade, M.; Deal, A. M.; Trembath, D.; McKee, M. J.; Brogi, E.; Seidman, A. D.
Article Title: Impact of prior systemic therapy on lymphocytic infiltration in surgically resected breast cancer brain metastases
Abstract: Purpose: Tumor-infiltrating lymphocytes (TILs) have been positively correlated with response to systemic therapy for triple-negative and HER2 + subtypes and improved clinical outcomes in early breast cancer (BC). Less is known about TILs in metastatic sites, particularly brain metastases (BM), where unique immune regulation governs stromal composition. Reactive glial cells actively participate in cytokine-mediated T cell stimulation. The impact of prior medical therapy (chemotherapy, endocrine, and HER2-targeted therapy) on the presence of TILs and gliosis in human breast cancer brain metastases (BCBM) has not been previously reported. Methods: We examined prior treatment data for 133 patients who underwent craniotomy for resection of BMs from the electronic medical record. The primary endpoint was overall survival (OS) from the time of BM diagnosis. We examined the relationship between prior systemic therapy exposure and the histologic features of gliosis, necrosis, hemorrhage, and lymphocyte infiltration (LI) in BCBMs resected at subsequent craniotomy in univariate analyses. Results: Complete treatment data were available for 123 patients. BCBM LI was identified in 35 of 116 (30%) patients who had received prior systemic treatment versus 5 of 7 (71.4%) who had not {significant by Fisher’s exact test p = 0.045}. There were no statistically significant relationships between prior systemic therapy and the three other histologic variables examined. Conclusions: This observation suggests that systemic therapy may interfere with the immune response to BCBMs and cause exhaustion of anti-tumor immunity. This motivates clinical investigation of strategies to enhance LI for therapeutic benefit to improve outcomes for patients with BCBMs. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: adult; cancer chemotherapy; controlled study; human tissue; middle aged; cancer surgery; excision; human cell; major clinical study; overall survival; histopathology; systemic therapy; cancer patient; brain tumor; brain neoplasms; antineoplastic agent; cancer diagnosis; tumor associated leukocyte; lymphocytes, tumor-infiltrating; breast cancer; epidermal growth factor receptor 2; gliosis; cohort analysis; pathology; breast neoplasms; retrospective study; cancer hormone therapy; electronic medical record; immune response; breast tumor; brain metastasis; tumor immunity; receptor, erbb-2; craniotomy; lymphocytic infiltration; observational study; trastuzumab; univariate analysis; tumor bleeding; tumor-infiltrating lymphocytes; tumor microenvironment; molecularly targeted therapy; tissue necrosis; clinical outcome; humans; prognosis; human; female; article
Journal Title: Breast Cancer Research and Treatment
Volume: 199
Issue: 1
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2023-05-01
Start Page: 99
End Page: 107
Language: English
DOI: 10.1007/s10549-023-06908-0
PUBMED: 36930347
PROVIDER: scopus
PMCID: PMC10865424
DOI/URL:
Notes: Article -- Export Date: 31 May 2023 -- Source: Scopus
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  1. Andrew D Seidman
    318 Seidman
  2. Edi Brogi
    515 Brogi
  3. Yuan Chen
    38 Chen