TY - JOUR
T1 - Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy
AU - de Jong, Vincent M T
AU - Wang, Yuwei
AU - Ter Hoeve, Natalie D
AU - Opdam, Mark
AU - Stathonikos, Nikolas
AU - Jóźwiak, Katarzyna
AU - Hauptmann, Michael
AU - Cornelissen, Sten
AU - Vreuls, Willem
AU - Rosenberg, Efraim H
AU - Koop, Esther A
AU - Varga, Zsuzsanna
AU - van Deurzen, Carolien H M
AU - Mooyaart, Antien L
AU - Córdoba, Alicia
AU - Groen, Emma J
AU - Bart, Joost
AU - Willems, Stefan M
AU - Zolota, Vasiliki
AU - Wesseling, Jelle
AU - Sapino, Anna
AU - Chmielik, Ewa
AU - Ryska, Ales
AU - Broeks, Annegien
AU - Voogd, Adri C
AU - Loi, Sherene
AU - Michiels, Stefan
AU - Sonke, Gabe S
AU - van der Wall, Elsken
AU - Siesling, Sabine
AU - van Diest, Paul J
AU - Schmidt, Marjanka K
AU - Kok, Marleen
AU - Dackus, Gwen M H E
AU - Salgado, Roberto
AU - Linn, Sabine C
PY - 2022/7/20
Y1 - 2022/7/20
N2 - 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-naive, 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 (chi(2) = 46.7, P < .001).CONCLUSION Chemotherapy-naive, 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. (c) 2022 by American Society of Clinical Oncology
AB - 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-naive, 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 (chi(2) = 46.7, P < .001).CONCLUSION Chemotherapy-naive, 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. (c) 2022 by American Society of Clinical Oncology
KW - GERMLINE MUTATIONS
KW - SURVIVAL OUTCOMES
KW - CHEMOTHERAPY
KW - TRIAL
KW - HISTOPATHOLOGY
KW - IMPACT
U2 - 10.1200/JCO.21.01536
DO - 10.1200/JCO.21.01536
M3 - Article
C2 - 35353548
SN - 0732-183X
VL - 40
SP - 2361
EP - 2375
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 21
ER -