Yukie Fujimoto1, Takahiro Watanabe2, Akira I Hida3, Tomoko Higuchi1, Yoshimasa Miyagawa1, Hiromi Ozawa1, Ayako Bun1, Reiko Fukui1, Atsushi Sata1, Michiko Imamura1, Seiichi Hirota2, Yasuo Miyoshi4. 1. Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya City, Hyogo, 663-8501, Japan. 2. Department of Surgical Pathology, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya City, Hyogo, 663-8501, Japan. 3. Department of Pathology, Matsuyama Shimin Hospital, 2-6-5 Otemachi, Matsuyama, Ehime, 790-0067, Japan. 4. Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya City, Hyogo, 663-8501, Japan. ymiyoshi@hyo-med.ac.jp.
Abstract
BACKGROUND: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been established in breast cancers with estrogen receptor (ER)-negative and human epithelial growth factor receptor 2 (HER2)-negative or HER2-positive subtypes; however, its utility concerning the ER + /HER2 - subtype remains unclear. METHODS: We evaluated the prognostic value of TILs by analyzing 717 invasive breast cancer operation cases. TILs were classified into three groups based on the proportion of area within the tumor: low ( < 10%), intermediate (10-50%), and high ( > 50%). Disease-free survival (DFS) and overall survival (OS) were calculated according to TIL levels. RESULTS: Although there was no significant association between TIL levels and DFS or OS in all patients, high TILs were significantly associated with favorable DFS in Ki67-high (n = 238, p = 0.035) but not in Ki67-low (n = 470, p = 0.46) breast cancers. Multivariable analysis showed that high TILs were a significant and independent factor for DFS (HR 0.34; 95% CI 0.10-0.87; p = 0.023) among the Ki67-high group. In the ER + /HER2 - subtype, high-TILs showed favorable DFS in the Ki67-high group, although this was not statistically significant (p = 0.48); in contrast, unfavorable DFS was observed in the Ki67-low group (p = 0.027). CONCLUSIONS: In Ki67-high breast cancers, high TILs were associated with favorable DFS, irrespective of subtype, but increasing TIL levels correlated with worse DFS in the Ki67-low group with the ER + /HER2 - subtype. These results highlight variation in TIL prognostic significance between Ki67-high and -low breast cancers, particularly for the ER + /HER2 - subtype.
BACKGROUND: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been established in breast cancers with estrogen receptor (ER)-negative and human epithelial growth factor receptor 2 (HER2)-negative or HER2-positive subtypes; however, its utility concerning the ER + /HER2 - subtype remains unclear. METHODS: We evaluated the prognostic value of TILs by analyzing 717 invasive breast cancer operation cases. TILs were classified into three groups based on the proportion of area within the tumor: low ( < 10%), intermediate (10-50%), and high ( > 50%). Disease-free survival (DFS) and overall survival (OS) were calculated according to TIL levels. RESULTS: Although there was no significant association between TIL levels and DFS or OS in all patients, high TILs were significantly associated with favorable DFS in Ki67-high (n = 238, p = 0.035) but not in Ki67-low (n = 470, p = 0.46) breast cancers. Multivariable analysis showed that high TILs were a significant and independent factor for DFS (HR 0.34; 95% CI 0.10-0.87; p = 0.023) among the Ki67-high group. In the ER + /HER2 - subtype, high-TILs showed favorable DFS in the Ki67-high group, although this was not statistically significant (p = 0.48); in contrast, unfavorable DFS was observed in the Ki67-low group (p = 0.027). CONCLUSIONS: In Ki67-high breast cancers, high TILs were associated with favorable DFS, irrespective of subtype, but increasing TIL levels correlated with worse DFS in the Ki67-low group with the ER + /HER2 - subtype. These results highlight variation in TIL prognostic significance between Ki67-high and -low breast cancers, particularly for the ER + /HER2 - subtype.
Entities:
Keywords:
Breast cancer; Ki67; Prognosis; Tumor-infiltrating lymphocytes
Authors: Jing Zhang; Mustapha Abubakar; Pei Yuan; Hela Koka; Lei Guo; Xin Li; Xiaohong R Yang; Jianming Ying; Ning Lyu Journal: Am J Transl Res Date: 2021-11-15 Impact factor: 4.060
Authors: Signe Korsgaard Skriver; Maj-Britt Jensen; Ann Soegaard Knoop; Bent Ejlertsen; Anne-Vibeke Laenkholm Journal: Breast Cancer Res Date: 2020-05-14 Impact factor: 6.466