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Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

VMT. de Jong, Y. Wang, ND. Ter Hoeve, M. Opdam, N. Stathonikos, K. Jóźwiak, M. Hauptmann, S. Cornelissen, W. Vreuls, EH. Rosenberg, EA. Koop, Z. Varga, CHM. van Deurzen, AL. Mooyaart, A. Córdoba, EJ. Groen, J. Bart, SM. Willems, V. Zolota, J....

. 2022 ; 40 (21) : 2361-2374. [pub] 20220330

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22025178

PURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies.

Cancer Center University Medical Center Utrecht Utrecht the Netherlands

Candiolo Cancer Institute FPO IRCCS Candiolo Italy

Charles University Medical Faculty and University Hospital Hradec Kralove Czech Republic

Core Facility Molecular Pathology and Biobanking Netherlands Cancer Institute Amsterdam the Netherlands

Departement of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland

Department of Clinical Genetics Leiden University Medical Centre Leiden the Netherlands

Department of Epidemiology Maastricht University Maastricht the Netherlands

Department of Health Technology and Services Research Technical Medical Centre University of Twente Enschede the Netherlands

Department of Medical Oncology Netherlands Cancer Institute Amsterdam the Netherlands

Department of Medical Sciences University of Torino Torino Italy

Department of Molecular Pathology Netherlands Cancer Institute Amsterdam the Netherlands

Department of Pathology Canisius Wilhelmina Ziekenhuis Nijmegen the Netherlands

Department of Pathology Complejo Hospitalario de Navarra Pamplona Spain

Department of Pathology Erasmus University Medical Center Rotterdam Rotterdam the Netherlands

Department of Pathology Gelre Ziekenhuizen Apeldoorn the Netherlands

Department of Pathology GZA ZNA Hospitals Antwerp Belgium

Department of Pathology Leiden University Medical Center Leiden the Netherlands

Department of Pathology Netherlands Cancer Institute Amsterdam the Netherlands

Department of Pathology Rion University Hospital Patras Greece

Department of Research and Development Netherlands Comprehensive Cancer Organization Utrecht the Netherlands

Division of Clinical Medicine and Research Peter MacCallum Cancer Centre Melbourne Australia

Division of Pathology University Medical Center Utrecht Utrecht the Netherlands

Institute of Biostatistics and Registry Research Brandenburg Medical School Theodor Fontane Neuruppin Germany

Service de Biostatistique et d'Epidémiologie Gustave Roussy Oncostat U1018 Inserm Paris Saclay University labeled Ligue Contre le Cancer Villejuif France

Tumor Pathology Department Maria Sklodowska Curie Memorial National Research Institute of Oncology Gliwice Poland

University of Groningen University Medical Center Groningen Department of Pathology and Medical Biology Groningen the Netherlands

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$a Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy / $c VMT. de Jong, Y. Wang, ND. Ter Hoeve, M. Opdam, N. Stathonikos, K. Jóźwiak, M. Hauptmann, S. Cornelissen, W. Vreuls, EH. Rosenberg, EA. Koop, Z. Varga, CHM. van Deurzen, AL. Mooyaart, A. Córdoba, EJ. Groen, J. Bart, SM. Willems, V. Zolota, J. Wesseling, A. Sapino, E. Chmielik, A. Ryska, A. Broeks, AC. Voogd, S. Loi, S. Michiels, GS. Sonke, E. van der Wall, S. Siesling, PJ. van Diest, MK. Schmidt, M. Kok, GMHE. Dackus, R. Salgado, SC. Linn
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$a PURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies.
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