Tumor-Infiltrating Lymphocytes in Patients With Stage I Triple-Negative Breast Cancer Untreated With Chemotherapy

Geurts, VCM; Balduzzi, S; Steenbruggen, TG; Linn, SC; Siesling, S; Badve, SS; DeMichele, A; Ignatiadis, M; Leon-Ferre, RA; Goetz, MP; Wolff, AC; Klar, N; Michiels, S; Loi, S; Adams, S; Horlings, HM; Sonke, GS; Salgado, R; Kok, M

Author(s): Geurts, VCM; Balduzzi, S; Steenbruggen, TG; Linn, SC; Siesling, S; Badve, SS; DeMichele, A; Ignatiadis, M; Leon-Ferre, RA; Goetz, MP; Wolff, AC; Klar, N; Michiels, S; Loi, S; Adams, S; Horlings, HM; Sonke, GS; Salgado, R; Kok, M;
Details: Publication Year 2024-08-01,Volume 10,Issue #8,Page 1077-1086
Journal Title: JAMA Oncology
Publication Type: Research article
Abstract: IMPORTANCE: The absolute benefit of chemotherapy for all patients with stage I triple-negative breast cancer (TNBC) is unclear, and biomarkers are not currently available for selecting patients with an excellent outcome for whom neoadjuvant or adjuvant chemotherapy may have negligible benefit. High levels of stromal tumor-infiltrating lymphocytes (sTILs) are associated with favorable survival in TNBC, but data solely in stage I TNBC are lacking. OBJECTIVE: To examine the outcomes of patients of all ages with stage I TNBC solely and who received neither neoadjuvant nor adjuvant chemotherapy, according to centrally reviewed sTIL levels at prespecified cutoffs. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Netherlands Cancer Registry to identify patients diagnosed with stage I TNBC between January 1, 2005, and December 31, 2015, who were not treated with chemotherapy. Only patients who did not receive neoadjuvant and/or adjuvant chemotherapy were selected. The clinical data were matched with their corresponding pathology data provided by the Dutch Pathology Registry. Data analysis was performed between February and October 2023. MAIN OUTCOMES AND MEASURES: The primary end point was breast cancer-specific survival (BCSS) at 5, 10, and 15 years for the prespecified sTIL level cutoffs of 30%, 50%, and 75%. Hematoxylin and eosin-stained slides were used for central review of histologic subtype, grade, and lymphovascular invasion. The International Immuno-Oncology Biomarker Working Group guidelines were used to score the sTIL levels; these levels were determined for 1041 patients. RESULTS: Of a total of 4511 females with stage I TNBC, patients who were not treated with chemotherapy were selected and tissue blocks requested; sTILs were scored in 1041 patients (mean [SD] age at diagnosis, 64.4 [11.1] years, median follow-up 11.4 [95% CI, 10.9-11.9] years) who were included in the analyses.. Most tumors (952 [91.5%]) were invasive carcinomas of nonspecial histologic subtype. Most patients (548 [52.6%]) had pT1cN0 tumors. Median (range) sTIL level was 5% (1%-99%). A total of 775 patients (74.4%) had sTIL levels below 30%, 266 (25.6%) had 30% or greater, 203 (19.5%) had 50% or greater, and 141 (13.5%) had 75% or greater. Patients with pT1abN0 tumors had a more favorable outcome vs patients with pT1cN0 tumors, with a 10-year BCSS of 92% (95% CI, 89%-94%) vs 86% (95% CI, 82%-89%). In the overall cohort, sTIL levels of at least 30% were associated with better BCSS compared with sTIL levels less than 30% (96% and 87%, respectively; hazard ratio [HR], 0.45; 95% CI, 0.26-0.77). High sTIL levels of 50% or greater were associated with a better outcome than low sTIL levels of less than 50% (HR, 0.27; 95% CI, 0.10-0.74) in patients with pT1C tumors, with a 10-year BCSS of 95% increasing to 98% with sTIL levels of 75% or greater. CONCLUSIONS AND RELEVANCE: Results of this study showed that patients with stage I TNBC and high level of sTILs who did not receive neoadjuvant or adjuvant chemotherapy had excellent 10-year BCSS. The findings further support the role of sTILs as integral biomarkers in prospective clinical trials of therapy optimization for this patient population.
Publisher: JAMA Network
Keywords: Humans; *Triple Negative Breast Neoplasms/drug therapy/pathology/immunology/mortality; *Lymphocytes, Tumor-Infiltrating/immunology; Female; Middle Aged; *Neoplasm Staging; Aged; Adult; Netherlands; Neoadjuvant Therapy; Chemotherapy, Adjuvant; Cohort Studies
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1001/jamaoncol.2024.1917
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-12 06:49:03

Last Modified: 2024-09-12 06:49:36