Immune Infiltration in Invasive Lobular Breast Cancer

Christine Desmedt, Roberto Salgado, Marco Fornili, Giancarlo Pruneri, Gert Van den Eynden, Gabriele Zoppoli, Françoise Rothé, Laurence Buisseret, Soizic Garaud, Karen Willard-Gallo, David Brown, Yacine Bareche, Ghizlane Rouas, Christine Galant, François Bertucci, Sherene Loi, Giuseppe Viale, Angelo Di Leo, Andrew R Green, Ian O EllisEmad A Rakha, Denis Larsimont, Elia Biganzoli, Christos Sotiriou

Research output: Contribution to journalArticle

Abstract

Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.

Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.

Results: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.

Conclusions: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.

Original languageEnglish
Pages (from-to)768-776
Number of pages9
JournalJournal of the National Cancer Institute
Volume110
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Breast Neoplasms
Tumor-Infiltrating Lymphocytes
Neoplasms
Estrogen Receptors
Atlases
Lymph Nodes
Genome
Confidence Intervals

Cite this

Desmedt, C., Salgado, R., Fornili, M., Pruneri, G., Van den Eynden, G., Zoppoli, G., ... Sotiriou, C. (2018). Immune Infiltration in Invasive Lobular Breast Cancer. Journal of the National Cancer Institute, 110(7), 768-776. https://doi.org/10.1093/jnci/djx268

Immune Infiltration in Invasive Lobular Breast Cancer. / Desmedt, Christine; Salgado, Roberto; Fornili, Marco; Pruneri, Giancarlo; Van den Eynden, Gert; Zoppoli, Gabriele; Rothé, Françoise; Buisseret, Laurence; Garaud, Soizic; Willard-Gallo, Karen; Brown, David; Bareche, Yacine; Rouas, Ghizlane; Galant, Christine; Bertucci, François; Loi, Sherene; Viale, Giuseppe; Di Leo, Angelo; Green, Andrew R; Ellis, Ian O; Rakha, Emad A; Larsimont, Denis; Biganzoli, Elia; Sotiriou, Christos.

In: Journal of the National Cancer Institute, Vol. 110, No. 7, 01.07.2018, p. 768-776.

Research output: Contribution to journalArticle

Desmedt, C, Salgado, R, Fornili, M, Pruneri, G, Van den Eynden, G, Zoppoli, G, Rothé, F, Buisseret, L, Garaud, S, Willard-Gallo, K, Brown, D, Bareche, Y, Rouas, G, Galant, C, Bertucci, F, Loi, S, Viale, G, Di Leo, A, Green, AR, Ellis, IO, Rakha, EA, Larsimont, D, Biganzoli, E & Sotiriou, C 2018, 'Immune Infiltration in Invasive Lobular Breast Cancer', Journal of the National Cancer Institute, vol. 110, no. 7, pp. 768-776. https://doi.org/10.1093/jnci/djx268
Desmedt C, Salgado R, Fornili M, Pruneri G, Van den Eynden G, Zoppoli G et al. Immune Infiltration in Invasive Lobular Breast Cancer. Journal of the National Cancer Institute. 2018 Jul 1;110(7):768-776. https://doi.org/10.1093/jnci/djx268
Desmedt, Christine ; Salgado, Roberto ; Fornili, Marco ; Pruneri, Giancarlo ; Van den Eynden, Gert ; Zoppoli, Gabriele ; Rothé, Françoise ; Buisseret, Laurence ; Garaud, Soizic ; Willard-Gallo, Karen ; Brown, David ; Bareche, Yacine ; Rouas, Ghizlane ; Galant, Christine ; Bertucci, François ; Loi, Sherene ; Viale, Giuseppe ; Di Leo, Angelo ; Green, Andrew R ; Ellis, Ian O ; Rakha, Emad A ; Larsimont, Denis ; Biganzoli, Elia ; Sotiriou, Christos. / Immune Infiltration in Invasive Lobular Breast Cancer. In: Journal of the National Cancer Institute. 2018 ; Vol. 110, No. 7. pp. 768-776.
@article{1ecaa46b6e104e8886c8f6b4263d82fa,
title = "Immune Infiltration in Invasive Lobular Breast Cancer",
abstract = "Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.Results: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95{\%} confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.Conclusions: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.",
author = "Christine Desmedt and Roberto Salgado and Marco Fornili and Giancarlo Pruneri and {Van den Eynden}, Gert and Gabriele Zoppoli and Fran{\cc}oise Roth{\'e} and Laurence Buisseret and Soizic Garaud and Karen Willard-Gallo and David Brown and Yacine Bareche and Ghizlane Rouas and Christine Galant and Fran{\cc}ois Bertucci and Sherene Loi and Giuseppe Viale and {Di Leo}, Angelo and Green, {Andrew R} and Ellis, {Ian O} and Rakha, {Emad A} and Denis Larsimont and Elia Biganzoli and Christos Sotiriou",
year = "2018",
month = "7",
day = "1",
doi = "10.1093/jnci/djx268",
language = "English",
volume = "110",
pages = "768--776",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - Immune Infiltration in Invasive Lobular Breast Cancer

AU - Desmedt, Christine

AU - Salgado, Roberto

AU - Fornili, Marco

AU - Pruneri, Giancarlo

AU - Van den Eynden, Gert

AU - Zoppoli, Gabriele

AU - Rothé, Françoise

AU - Buisseret, Laurence

AU - Garaud, Soizic

AU - Willard-Gallo, Karen

AU - Brown, David

AU - Bareche, Yacine

AU - Rouas, Ghizlane

AU - Galant, Christine

AU - Bertucci, François

AU - Loi, Sherene

AU - Viale, Giuseppe

AU - Di Leo, Angelo

AU - Green, Andrew R

AU - Ellis, Ian O

AU - Rakha, Emad A

AU - Larsimont, Denis

AU - Biganzoli, Elia

AU - Sotiriou, Christos

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.Results: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.Conclusions: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.

AB - Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.Results: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.Conclusions: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.

U2 - 10.1093/jnci/djx268

DO - 10.1093/jnci/djx268

M3 - Article

C2 - 29471435

VL - 110

SP - 768

EP - 776

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 7

ER -