Immune infiltration in invasive lobular breast cancer

Desmedt, Christine, Salgado, Roberto, Fornili, Marco, Pruneri, Giancarlo, Gert 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, Larsimont, Denis, Biganzoli, Elia M. and Sotiriou, Christos (2018) Immune infiltration in invasive lobular breast cancer. Journal of the National Cancer Institute . ISSN 1460-2105

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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 (TIL) and their association with clinico-pathological, and outcome variables in ILC, and to compare it with IDC.

Methods: We considered two patient series with TIL data: a multi-centric 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 TCGA patients. All ILC/IDC comparisons were done in ER-positive/HER2-negative tumors. All statistical tests were two-sided.

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

Conclusion: 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.

Item Type: Article
Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of the National Cancer Institute following peer review. The version of record 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 Ellis, Emad A Rakha, Denis Larsimont, Elia Biganzoli, Christos Sotiriou; Immune Infiltration in Invasive Lobular Breast Cancer, JNCI: Journal of the National Cancer Institute, , djx268, is available online at:
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
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Depositing User: Eprints, Support
Date Deposited: 12 Dec 2017 14:48
Last Modified: 20 Feb 2019 04:30

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