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

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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.

Original languageEnglish
Pages (from-to)83-88
Number of pages6
JournalBreast
Volume34
DOIs
Publication statusPublished - Aug 1 2017

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Tumor-Infiltrating Lymphocytes
Hormones
Breast Neoplasms
Drug Therapy
Cyclophosphamide
Disease-Free Survival
Neoplasms

Keywords

  • Breast cancer
  • Luminal
  • Metastatic
  • Metronomic therapy
  • Prognosis
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Surgery

Cite this

@article{7152c7b585fe46a0926d9e96d71fda96,
title = "Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy",
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.",
keywords = "Breast cancer, Luminal, Metastatic, Metronomic therapy, Prognosis, Tumor infiltrating lymphocytes",
author = "Emilia Montagna and Andrea Vingiani and Patrick Maisonneuve and Giuseppe Cancello and Federica Contaldo and Giancarlo Pruneri and Marco Colleoni",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.breast.2017.05.009",
language = "English",
volume = "34",
pages = "83--88",
journal = "Breast",
issn = "0960-9776",
publisher = "Churchill Livingstone",

}

TY - JOUR

T1 - Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy

AU - Montagna, Emilia

AU - Vingiani, Andrea

AU - Maisonneuve, Patrick

AU - Cancello, Giuseppe

AU - Contaldo, Federica

AU - Pruneri, Giancarlo

AU - Colleoni, Marco

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Luminal

KW - Metastatic

KW - Metronomic therapy

KW - Prognosis

KW - Tumor infiltrating lymphocytes

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U2 - 10.1016/j.breast.2017.05.009

DO - 10.1016/j.breast.2017.05.009

M3 - Article

VL - 34

SP - 83

EP - 88

JO - Breast

JF - Breast

SN - 0960-9776

ER -