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Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers

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Abstract

Background

The criteria for classifying hormone receptor (HR)-positive/HER2-negative breast cancers into low-risk and high-risk subgroups remain undetermined. Supportive data for optimal criteria to identify tumors in the high-risk subgroup are necessary for Japanese patients with HR-positive/HER2-negative breast cancers.

Methods

Using immunohistochemistry and fluorescence in situ hybridization, we identified 369 consecutive patients with HR-positive/HER2-negative, node-negative invasive breast cancers. We examined the prognostic impact of the Ki-67 labeling index (LI) based on 3 cutoff values, 10, 14, and 20 %, along with that of histological grade (HG) and nuclear grade (NG) by Cox’s univariate and multivariate analyses.

Results

The univariate analyses clearly showed that Ki-67 LI with any cutoff value divided the patients into distinct high-risk and low-risk groups, and that HG and NG were also powerful prognostic indicators. High Ki-67 LI with any cutoff value was strongly correlated with HG and NG, and when these parameters were included in the multivariate analyses, the impact of HG/NG was stronger than Ki-67 LIs. When the 10 % cutoff value was adopted, discordance between Ki-67 LI and grades was frequent in papillotubular-type invasive ductal carcinoma, predominantly intraductal carcinoma, and mucinous carcinoma.

Conclusions

Any of the Ki-67 LI values, regardless of cutoff value, could be applicable for the classification of high-risk and low-risk HR-positive/HER2-negative, node-negative invasive breast cancers. Luminal A/B subtyping according to Ki-67 LI, or HG/NG, in combination with histological type, appeared to be able to create an optimum risk estimation system for patients with HR-positive/HER2-negative, node-negative invasive breast cancers in Japan.

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Acknowledgments

This work was supported in part by the National Cancer Center Research and Development Fund (22-5), the Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (22501039), and Grant-in-Aid for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor, and Welfare, Japan (H22-023). We thank Sachiko Miura, M.T., Chizu Kina, M.T., Ms. Chinami Onuma (National Cancer Center Hospital), and Ms. Kozue Suzuki (National Defense Medical College) for technical support.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan

    Makiko Ono

  2. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hitoshi Tsuda

  3. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

    Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Kenji Tamura & Yasuhiro Fujiwara

  4. Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan

    Takayuki Kinoshita

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  1. Makiko Ono
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Correspondence to Hitoshi Tsuda.

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Ono, M., Tsuda, H., Yunokawa, M. et al. Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers. Breast Cancer 22, 141–152 (2015). https://doi.org/10.1007/s12282-013-0464-4

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  • DOI: https://doi.org/10.1007/s12282-013-0464-4

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