Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

Fujii,Kimihito; Watanabe,Rie; Ando,Takahito; Kousaka,Junko; Mouri,Yukako; Yoshida,Miwa; Imai,Tsuneo; Nakano,Shogo; Fukutomi,Takashi

doi:10.3892/br.2017.1003

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

Authors:
- Kimihito Fujii
- Rie Watanabe
- Takahito Ando
- Junko Kousaka
- Yukako Mouri
- Miwa Yoshida
- Tsuneo Imai
- Shogo Nakano
- Takashi Fukutomi
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Affiliations: Division of Breast and Endocrine Surgery, Department of Surgery, Aichi Medical University, Nagakute, Aichi 480-1195, Japan, Department of Breast Surgery, Yodogawa Christian Hospital, Higashi Yodogawa Ku, Osaka 533-0024, Japan, Breast Clinic, Showa University Koto Toyosu Hospital, Koto ku, Tokyo 135-8577, Japan, Department of Surgery, Higashinagoya National Hospital, Meito ku, Nagoya, Aichi 465-8620, Japan, Department of Surgery, Saiseikai Central Hospital, Minato ku, Tokyo 108-0073, Japan
Published online on: October 19, 2017 https://doi.org/10.3892/br.2017.1003
Pages: 535-542

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Abstract

In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

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