Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer

M Kochi, T Iwamoto, N Niikura, G Bianchini, S Masuda, T Mizoo, T Nogami, T Shien, T Motoki, N Taira, Y Tokuda, H Doihara, J Matsuoka, T Fujiwara

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Abstract

Purpose: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. Methods: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies. Results: Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P < 0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95% CI 1.30–3.14, P = 0.025). Conclusions: TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes. © 2017 Springer Science+Business Media, LLC
Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalBreast Cancer Research and Treatment
Volume167
Issue number1
DOIs
Publication statusPublished - 2018

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Tumor-Infiltrating Lymphocytes
Breast Neoplasms
Drug Therapy
Hematoxylin
Eosine Yellowish-(YS)
Neoplasms
Anthracyclines
Gene Expression Profiling
Transcriptome

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Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer. / Kochi, M; Iwamoto, T; Niikura, N; Bianchini, G; Masuda, S; Mizoo, T; Nogami, T; Shien, T; Motoki, T; Taira, N; Tokuda, Y; Doihara, H; Matsuoka, J; Fujiwara, T.

In: Breast Cancer Research and Treatment, Vol. 167, No. 1, 2018, p. 39-47.

Research output: Contribution to journalArticle

Kochi, M, Iwamoto, T, Niikura, N, Bianchini, G, Masuda, S, Mizoo, T, Nogami, T, Shien, T, Motoki, T, Taira, N, Tokuda, Y, Doihara, H, Matsuoka, J & Fujiwara, T 2018, 'Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer', Breast Cancer Research and Treatment, vol. 167, no. 1, pp. 39-47. https://doi.org/10.1007/s10549-017-4502-3
Kochi, M ; Iwamoto, T ; Niikura, N ; Bianchini, G ; Masuda, S ; Mizoo, T ; Nogami, T ; Shien, T ; Motoki, T ; Taira, N ; Tokuda, Y ; Doihara, H ; Matsuoka, J ; Fujiwara, T. / Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer. In: Breast Cancer Research and Treatment. 2018 ; Vol. 167, No. 1. pp. 39-47.
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abstract = "Purpose: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. Methods: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies. Results: Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P < 0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95{\%} CI 1.30–3.14, P = 0.025). Conclusions: TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes. {\circledC} 2017 Springer Science+Business Media, LLC",
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AU - Iwamoto, T

AU - Niikura, N

AU - Bianchini, G

AU - Masuda, S

AU - Mizoo, T

AU - Nogami, T

AU - Shien, T

AU - Motoki, T

AU - Taira, N

AU - Tokuda, Y

AU - Doihara, H

AU - Matsuoka, J

AU - Fujiwara, T

PY - 2018

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N2 - Purpose: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. Methods: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies. Results: Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P < 0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95% CI 1.30–3.14, P = 0.025). Conclusions: TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes. © 2017 Springer Science+Business Media, LLC

AB - Purpose: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. Methods: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies. Results: Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P < 0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95% CI 1.30–3.14, P = 0.025). Conclusions: TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes. © 2017 Springer Science+Business Media, LLC

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JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

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