Background: High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown.Patients and methods: We evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination).Results: Of the 108 ER + BC patients enrolled in the VEX trial, 92 (85%) had sufficient tumor tissue and were assessed for TILs in H&E stained slides. TILs were evaluated in 38 primary BC samples and 54 metastatic sites. High (>= 10%) TILs levels were significantly correlated with high Ki-67 labeling index. At multivariable analysis, each 10% increase in TILs strongly predicted a worse TTP (HR: 1.27, p = 0.008). VEX trial patients, categorized by a 3 tiers system (0-4%, 5-9% and >10% TILs) showed significantly different progression free survival curves (p = 0.011).Conclusions: High TILs levels are significantly associated with a worse TTP in Luminal metastatic BC patients treated by metronomic chemotherapy. Our data confirm the reliability of TILs as a biomarker in the BC metastatic setting. The putative unfavorable prognostic role of TILs in Luminal BC patients might have clinical utility if validated by further studies.

Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy / E. Montagna, A. Vingiani, P. Maisonneuve, G. Cancello, F. Contaldo, G. Pruneri, M. Colleoni. - In: THE BREAST. - ISSN 0960-9776. - 34:(2017), pp. 83-88. [10.1016/j.breast.2017.05.009]

Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy

A. Vingiani
Secondo
;
G. Pruneri
Penultimo
;
2017

Abstract

Background: High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown.Patients and methods: We evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination).Results: Of the 108 ER + BC patients enrolled in the VEX trial, 92 (85%) had sufficient tumor tissue and were assessed for TILs in H&E stained slides. TILs were evaluated in 38 primary BC samples and 54 metastatic sites. High (>= 10%) TILs levels were significantly correlated with high Ki-67 labeling index. At multivariable analysis, each 10% increase in TILs strongly predicted a worse TTP (HR: 1.27, p = 0.008). VEX trial patients, categorized by a 3 tiers system (0-4%, 5-9% and >10% TILs) showed significantly different progression free survival curves (p = 0.011).Conclusions: High TILs levels are significantly associated with a worse TTP in Luminal metastatic BC patients treated by metronomic chemotherapy. Our data confirm the reliability of TILs as a biomarker in the BC metastatic setting. The putative unfavorable prognostic role of TILs in Luminal BC patients might have clinical utility if validated by further studies.
Breast cancer; Luminal; Metastatic; Metronomic therapy; Tumor infiltrating lymphocytes; Prognosis;
Settore MED/06 - Oncologia Medica
Settore MED/08 - Anatomia Patologica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/939386
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