Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials

M. V. Dieci, M. C. Mathieu, V. Guarneri, P. Conte, S. Delaloge, F. Andre, Aicha Goubar

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. Patients and methods: A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. Results: TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P <0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20- 1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-). Conclusions: We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.

Original languageEnglish
Pages (from-to)1698-1704
Number of pages7
JournalAnnals of Oncology
Volume26
Issue number8
DOIs
Publication statusPublished - 2015

Fingerprint

Tumor-Infiltrating Lymphocytes
Breast Neoplasms
Anthracyclines
Estrogen Receptors
Confidence Intervals
Triple Negative Breast Neoplasms
Drug Therapy

Keywords

  • Adjuvant chemotherapy
  • Anthracyclines
  • Breast cancer
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. / Dieci, M. V.; Mathieu, M. C.; Guarneri, V.; Conte, P.; Delaloge, S.; Andre, F.; Goubar, Aicha.

In: Annals of Oncology, Vol. 26, No. 8, 2015, p. 1698-1704.

Research output: Contribution to journalArticle

Dieci, M. V. ; Mathieu, M. C. ; Guarneri, V. ; Conte, P. ; Delaloge, S. ; Andre, F. ; Goubar, Aicha. / Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. In: Annals of Oncology. 2015 ; Vol. 26, No. 8. pp. 1698-1704.
@article{c722272bf5af4f91a1d450b6398b688e,
title = "Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials",
abstract = "Background: Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. Patients and methods: A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. Results: TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P <0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95{\%} confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95{\%} CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89{\%} and 68{\%} for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95{\%} CI 0.18-1.10, P = 0.07) and 78{\%} and 57{\%} for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95{\%} CI 0.20- 1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-). Conclusions: We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.",
keywords = "Adjuvant chemotherapy, Anthracyclines, Breast cancer, Tumor-infiltrating lymphocytes",
author = "Dieci, {M. V.} and Mathieu, {M. C.} and V. Guarneri and P. Conte and S. Delaloge and F. Andre and Aicha Goubar",
year = "2015",
doi = "10.1093/annonc/mdv239",
language = "English",
volume = "26",
pages = "1698--1704",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "8",

}

TY - JOUR

T1 - Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials

AU - Dieci, M. V.

AU - Mathieu, M. C.

AU - Guarneri, V.

AU - Conte, P.

AU - Delaloge, S.

AU - Andre, F.

AU - Goubar, Aicha

PY - 2015

Y1 - 2015

N2 - Background: Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. Patients and methods: A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. Results: TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P <0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20- 1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-). Conclusions: We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.

AB - Background: Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. Patients and methods: A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. Results: TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P <0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20- 1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-). Conclusions: We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.

KW - Adjuvant chemotherapy

KW - Anthracyclines

KW - Breast cancer

KW - Tumor-infiltrating lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=84941623486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941623486&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdv239

DO - 10.1093/annonc/mdv239

M3 - Article

VL - 26

SP - 1698

EP - 1704

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 8

ER -