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, Francois; Loi, Sherene; Viale, Giuseppe; Di Leo, Angelo; Green, Andrew R.; Ellis, Ian O.; Rakha, Emad A.; Larsimont, Denis; Biganzoli, Elia; Sotiriou, Christos

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 (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.

Citation

Desmedt, C., Salgado, R., Fornili, M., Pruneri, G., Gert 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, A. R., Ellis, I. O., …Sotiriou, C. (2018). Immune infiltration in invasive lobular breast cancer. JNCI: Journal of the National Cancer Institute, 110(7), 768–776. https://doi.org/10.1093/jnci/djx268

• Journal Article Type: Article
• Acceptance Date: Nov 20, 2017
• Online Publication Date: Feb 20, 2018
• Publication Date: Jul 1, 2018
• Deposit Date: Dec 12, 2017
• Publicly Available Date: Aug 10, 2018
• Journal: Journal of the National Cancer Institute
• Print ISSN: 0027-8874
• Electronic ISSN: 1460-2105
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 110
• Issue: 7
• Pages: 768–776
• DOI: https://doi.org/10.1093/jnci/djx268
• Public URL: https://nottingham-repository.worktribe.com/output/912394
• Publisher URL: https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djx268/4881757
• Contract Date: Aug 10, 2018