Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor‑positive/human epidermal growth factor receptor type 2 negative breast cancer

Miyoshi,Yuichiro; Shien,Tadahiko; Ogiya,Akiko; Ishida,Naoko; Yamazaki,Kieko; Horii,Rie; Horimoto,Yoshiya; Masuda,Norikazu; Yasojima,Hiroyuki; Inao,Touko; Osako,Tomofumi; Takahashi,Masato; Tomioka,Nobumoto; Wanifuchi‑Endo,Yumi; Hosoda,Mitsuchika; Doihara,Hiroyoshi; Yamashita,Hiroko

doi:10.3892/ol.2018.9853

Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor‑positive/human epidermal growth factor receptor type 2 negative breast cancer

Authors:
- Yuichiro Miyoshi
- Tadahiko Shien
- Akiko Ogiya
- Naoko Ishida
- Kieko Yamazaki
- Rie Horii
- Yoshiya Horimoto
- Norikazu Masuda
- Hiroyuki Yasojima
- Touko Inao
- Tomofumi Osako
- Masato Takahashi
- Nobumoto Tomioka
- Yumi Wanifuchi‑Endo
- Mitsuchika Hosoda
- Hiroyoshi Doihara
- Hiroko Yamashita
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Affiliations: Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama 700‑8558, Japan, Department of Breast Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135‑8550, Japan, Department of Breast Surgery, Hokkaido University Hospital, Hokkaido 060‑8648, Japan, Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135‑8550, Japan, Department of Breast Oncology, Juntendo University School of Medicine, Tokyo 113‑8431, Japan, Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka 540‑0006, Japan, Department of Breast and Endocrine Surgery, Graduate School of Medical Science Kumamoto University, Kumamoto 860‑8556, Japan, Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto 862‑8505, Japan, Department of Breast Surgery, NHO Hokkaido Cancer Center, Hokkaido 003‑0804, Japan, Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan
Published online on: December 19, 2018 https://doi.org/10.3892/ol.2018.9853
Pages: 2177-2186
Copyright: © Miyoshi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The value of assessing tumor infiltrating lymphocytes (TILs) in estrogen receptor (ER) positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer has yet to be determined. In the present study, a total of 184 cases with early distant recurrence detected within 5 years following the primary operation, 134 with late distant recurrence diagnosed following 5 years or longer and 321 controls without recurrence for >10 years following starting the initial treatment for ER‑positive/HER2 negative breast cancer, registered in 9 institutions, were analyzed. The distributions of TILs and their clinical relevance were investigated. TIL distributions did not differ significantly among the early, late and no recurrence groups, employing a 30% cut‑off point as a dichotomous variable. In those who had received adjuvant chemotherapy as well as endocrine therapy, a trend toward higher TIL proportions was detected when the early recurrence group was compared with the no recurrence group employing the 30% cut‑off point (P=0.064). The TIL distributions were significantly associated with nodal metastasis (P=0.004), ER status (P=0.045), progesterone receptor (PgR) status (P=0.002), tumor grade (P=0.021), and the Ki67 labeling index (LI) (P=0.002) in the no recurrence group and with the Ki67 LI in the recurrence groups (P=0.002 in early recurrence group, P=0.023 in late recurrence group). High TIL distributions also predicted shorter survival time following the detection of recurrence (P=0.026). However, these prognostic interactions were not significant in multivariate analysis (P=0.200). The present retrospective study demonstrated no significant interaction between TIL proportions and the timing of recurrence. However, higher TIL proportions were observed in breast cancer patients with aggressive biological phenotypes, which tended to be more responsive to chemotherapy. The clinical relevance of stromal TILs for identifying patients who would likely benefit from additional therapies merits further investigation in a larger patient population.

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