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Clinical Importance of Estrogen Receptor-β Evaluation in Breast Cancer Patients Treated With Adjuvant Tamoxifen Therapy

Naoko Honma, Rie Horii, Takuji Iwase, Shigehira Saji, Mamoun Younes, Kaiyo Takubo, Masaaki Matsuura, Yoshinori Ito, Futoshi Akiyama, Goi Sakamoto

From the Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology; Departments of Breast Pathology and Cancer Genomics, Cancer Institute; Departments of Breast Oncology and Medical Oncology, Cancer Institute Hospital; Division of Clinical Trials and Research, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; and the Department of Pathology, Baylor College of Medicine, Houston, TX

Corresponding author: Naoko Honma, MD, Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Sakaecho 35-2, Itabashi-ku, Tokyo 173-0015, Japan; e-mail: nhonma{at}tmig.or.jp

Purpose The clinicopathologic importance of a second estrogen receptor (ER), ER-β, in breast cancers has been intensely studied; however, there is still no real consensus regarding the clinical utility of an ER-β assay, probably because of the lack of standardized methodology, the presence of several ER-β isotypes (ER-β1-5, and so on), and, more importantly, the lack of convincing data on whether the ER-β status provides clinically useful information over what is already provided by the traditional ER-/progesterone receptor (PR) assay. A large and systematic study is needed to address these important issues.

Patients and Methods Archival materials of 442 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and with a long follow-up period (median, 11.1 years) were subjected to immunohistochemical study using three commercially available anti–ER-β antibodies that detect ER-β1-3 (ER-βN), ER-β1, and ER-βcx (ER-β2).

Results Positive staining for ER-βN or ER-β1 was associated with significantly better survival. By contrast, ER-βcx status did not influence survival. In multivariate analysis, ER-β1 status emerged as an independent predictor of recurrence and mortality. ER-β1 status was significantly associated with survival in postmenopausal, but not premenopausal, women. Importantly, ER-β1 positivity was associated with significantly better survival in patients with ER-–negative/PR-negative or ER-–negative/PR–negative/human epidermal growth factor receptor 2–negative (triple-negative) tumors, which are widely believed to be hormone unresponsive, have poor prognosis, and require chemotherapy.

Conclusion Immunohistochemical examination of ER-β1 in addition to ER- and PR is clinically important in patients with breast cancer treated with tamoxifen monotherapy. Further studies are needed to confirm our findings.

Supported by Grant-in-Aid for Scientific Research No. 17590324 from the Japan Society for the Promotion of Science and Grant-in-Aid for Cancer Research No. 17-7 from the Ministry of Health, Labour and Welfare of Japan.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Clinical Importance of Estrogen Receptor β Isoforms in Breast Cancer
  Valerie Speirs, Andrew R. Green, Thomas A. Hughes, Ian O. Ellis, Philippa T.K. Saunders, and Abeer M. Shaaban
  JCO 2008 26: 5825 [Full Text]

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				V. Speirs, A. R. Green, T. A. Hughes, I. O. Ellis, P. T.K. Saunders, and A. M. Shaaban Clinical Importance of Estrogen Receptor {beta} Isoforms in Breast Cancer J. Clin. Oncol., December 10, 2008; 26(35): 5825 - 5825. [Full Text] [PDF]

				N. Honma, S. Saji, and M. Younes In Reply J. Clin. Oncol., December 10, 2008; 26(35): 5825 - 5826. [Full Text] [PDF]