Immune infiltration in invasive lobular breast cancer
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-patholog...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Oxford University Press
2018
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| Online Access: | https://eprints.nottingham.ac.uk/48695/ |
| _version_ | 1848797825253507072 |
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| author | 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. Sotiriou, Christos |
| author_facet | 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. Sotiriou, Christos |
| author_sort | Desmedt, Christine |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:10:01Z |
| format | Article |
| id | nottingham-48695 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:10:01Z |
| publishDate | 2018 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-486952024-08-15T15:26:45Z https://eprints.nottingham.ac.uk/48695/ 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. Sotiriou, Christos 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. Oxford University Press 2018-02-20 Article PeerReviewed 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 https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djx268/4881757 doi:10.1093/jnci/djx268 doi:10.1093/jnci/djx268 |
| spellingShingle | 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. Sotiriou, Christos Immune infiltration in invasive lobular breast cancer |
| title | Immune infiltration in invasive lobular breast cancer |
| title_full | Immune infiltration in invasive lobular breast cancer |
| title_fullStr | Immune infiltration in invasive lobular breast cancer |
| title_full_unstemmed | Immune infiltration in invasive lobular breast cancer |
| title_short | Immune infiltration in invasive lobular breast cancer |
| title_sort | immune infiltration in invasive lobular breast cancer |
| url | https://eprints.nottingham.ac.uk/48695/ https://eprints.nottingham.ac.uk/48695/ https://eprints.nottingham.ac.uk/48695/ |