Giuseppe Floris1, François Richard2, Anne-Sophie Hamy3, Lynn Jongen4, Hans Wildiers4,5, Jan Ardui6, Kevin Punie4,5, Ann Smeets4,7, Patrick Berteloot6, Ignace Vergote4,6, Diane De Croze8, Didier Meseure8, Anne Salomon8, Marick Laé9, Fabien Reyal3, Elia Biganzoli10, Patrick Neven4,6, Christine Desmedt2. 1. Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research and University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium. 2. Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, 3000 Leuven, Belgium. 3. Lab Residual Tumor and Response to Treatment, Université Paris-Descartes, Paris, France. 4. Department of Oncology, KU Leuven, 3000 Leuven, Belgium. 5. Department of General Medical Oncology, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium. 6. Department of Gynecology and Obstetrics, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium. 7. Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium. 8. Department of Pathology, Institut Curie, Paris, France. 9. Department of Pathology, Centre Henri Becquerel, INSERM U1245, UNIROUEN, University of Normandie, Rouen, France. 10. Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro," Department of Clinical Sciences and Community Health & Data Science Research Center (DSRC), University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Abstract
BACKGROUND: High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI). METHODS: sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445). sTIL and BMI were considered as binary (sTIL: <30.0% vs ≥30.0%; BMI: lean vs overweight and obese) and continuous variables. Associations with pCR (ypT0/isN0) were assessed using logistic regression, and associations with event-free survival and overall survival were assessed using Cox regressions. RESULTS: 236 (53.0%) patients were lean and 209 (47.0%) overweight and obese. pCR was achieved in 181 of 445 (41.7%) patients. Median sTIL was 11.0%, and 99 of 445 (22.2%) tumors had high sTIL. A statistically significant interaction between sTIL and BMI, considered as categorical or continuous variables, for predicting pCR was observed in the multivariable analysis (Pinteraction = .03 and .04, respectively). High sTIL were statistically significantly associated with pCR in lean (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.10 to 8.56; P < .001) but not in heavier patients (OR = 1.48, 95% CI = 0.75 to 2.91; P = .26) in the multivariable analysis. High sTIL were further associated with increased event-free survival in lean (hazard ratio [HR] = 0.22, 95% CI = 0.08 to 0.62; P = .004) but not in heavier patients (HR = 0.53, 95% CI = 0.26 to 1.08; P = .08). Similar results were obtained for overall survival. CONCLUSION: BMI is modifying the effect of sTIL on pCR and prognosis in TNBC patients treated with neoadjuvant chemotherapy.
BACKGROUND: High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI). METHODS: sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445). sTIL and BMI were considered as binary (sTIL: <30.0% vs ≥30.0%; BMI: lean vs overweight and obese) and continuous variables. Associations with pCR (ypT0/isN0) were assessed using logistic regression, and associations with event-free survival and overall survival were assessed using Cox regressions. RESULTS: 236 (53.0%) patients were lean and 209 (47.0%) overweight and obese. pCR was achieved in 181 of 445 (41.7%) patients. Median sTIL was 11.0%, and 99 of 445 (22.2%) tumors had high sTIL. A statistically significant interaction between sTIL and BMI, considered as categorical or continuous variables, for predicting pCR was observed in the multivariable analysis (Pinteraction = .03 and .04, respectively). High sTIL were statistically significantly associated with pCR in lean (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.10 to 8.56; P < .001) but not in heavier patients (OR = 1.48, 95% CI = 0.75 to 2.91; P = .26) in the multivariable analysis. High sTIL were further associated with increased event-free survival in lean (hazard ratio [HR] = 0.22, 95% CI = 0.08 to 0.62; P = .004) but not in heavier patients (HR = 0.53, 95% CI = 0.26 to 1.08; P = .08). Similar results were obtained for overall survival. CONCLUSION: BMI is modifying the effect of sTIL on pCR and prognosis in TNBC patients treated with neoadjuvant chemotherapy.
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