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Reduced Expression of the Breast Cancer Metastasis Suppressor 1 mRNA Is Correlated with Poor Progress in Breast Cancer

Authors' Affiliations: ¹ Department of Breast and Endocrine Surgery, Nagoya City University Hospital, Nagoya, Japan; ² Department of Breast and Endocrine Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; and ³ Department of General Surgery, First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, China

Requests for reprints: Hirotaka Iwase, Department of Breast and Endocrine Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan. Phone: 81-96-373-5521; Fax: 81-96-373-5525; E-mail: hiwase{at}kaiju.medic.kumamoto-u.ac.jp.

Purpose: It is well established that breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of breast cancer in animal models without affecting the growth of the primary tumor. It has also been shown to suppress the metastasis of tumors derived from breast and melanoma cell lines. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to clarify its clinical significance.

Experimental Design: The level of expression of BRMS1 mRNA was assessed by LightCycler quantitative real-time reverse transcription-PCR in 161 cases of invasive carcinoma of the breast. Associations between BRMS1 mRNA expression and various clinicopathologic factors were sought.

Results: It was found that BRMS1 mRNA was expressed at significantly higher levels in patients >50 years of age, with tumor size <2 cm, or with progesterone receptor–positive and HER2-negative tumors. No differences were found between BRMS1 mRNA expression and axillary lymph node metastasis and histologic grade groups. Patients with high levels of expression of BRMS1 mRNA have a better prognosis than those with low expression. Univariate and multivariate prognostic analysis showed that BRMS1 mRNA is an independent prognostic factor for disease-free survival in breast cancer.

Conclusions: These results provide clinical evidence to support the notion that BRMS1 is a breast carcinoma metastasis suppressor gene. Our results also suggest that measuring BRMS1 expression will help to identify those breast cancer patients with worse disease-free survival.

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