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Ki-67 evaluation at the hottest spot predicts clinical outcome of patients with hormone receptor-positive/HER2-negative breast cancer treated with adjuvant tamoxifen monotherapy

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Abstract

Background

The clinicopathological importance of Ki-67 in breast cancers has been intensely studied; however, there have been few systematic large studies of patients treated with predefined adjuvant therapy. Further, Ki-67 evaluation methodology differed among studies, which prevents Ki-67 from being used for clinical practice. We performed a large systematic study using routinely processed tissues and compared various scoring methods.

Methods

Representative slides of archival tissue blocks of 442 consecutive invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and having a long follow-up period were subjected to immunohistochemistry using anti-Ki-67 monoclonal antibody, Mib-1. Both the average score across the section and the score at the hottest spot were assessed.

Results

Ki-67 evaluated at the hottest spot, not the average score across the section, independently predicted poor clinical outcomes of patients with hormone receptor-positive/HER2-negative cancer. Ki-67 was not a predictor of clinical outcome in patients with triple-negative breast cancer. Overall, high Ki-67 level significantly correlated with classic unfavorable clinicopathological factors, correlating negatively with the status of estrogen receptor (ER)-α and progesterone receptor (PR), and positively with HER2 status and grade. ER-β status positively correlated with the Ki-67 level.

Conclusions

Ki-67 evaluation at the hottest spot was superior to that determined by average score across the section as a predictor of outcome in patients with hormone receptor-positive/HER2-negative breast cancers treated with endocrine monotherapy. The different result obtained in patients with triple-negative carcinomas needs to be further investigated.

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Acknowledgments

We thank Drs. Goi Sakamoto and Kaiyo Takubo for their administrative support, and Ms. Tomoyo Kakita, Ms. Mayumi Ogawa, Mr. Genkichi Iwakoshi, Ms. Kazuko Yokokawa, and the technical staff of the Department of Pathology, Cancer Institute for their excellent technical support. This work was supported by JSPS KAKENHI (17590324) and a grant-in-aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (No. 17-7).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan

    Naoko Honma

  2. Department of Pathology, Cancer Institute, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Naoko Honma, Rie Horii & Futoshi Akiyama

  3. Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Takuji Iwase

  4. Department of Target Therapy Oncology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Shigehira Saji

  5. Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, 6413 Fannin, Houston, TX, 77030, USA

    Mamoun Younes

  6. Breast Medical Oncology, Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Yoshinori Ito

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  1. Naoko Honma
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Correspondence to Naoko Honma.

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Honma, N., Horii, R., Iwase, T. et al. Ki-67 evaluation at the hottest spot predicts clinical outcome of patients with hormone receptor-positive/HER2-negative breast cancer treated with adjuvant tamoxifen monotherapy. Breast Cancer 22, 71–78 (2015). https://doi.org/10.1007/s12282-013-0455-5

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  • DOI: https://doi.org/10.1007/s12282-013-0455-5

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