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Cyclin D1 Expression in Breast Cancer Patients Receiving Adjuvant Tamoxifen-Based Therapy

Authors' Affiliations: Departments of ¹ Pathology, ² Medicine I, ³ Surgery, and ⁴ Special Gynecology, Medical University of Vienna; Departments of ⁵ Pathology and Microbiology and ⁶ Surgery, Hanusch Medical Center, Vienna, Austria; ⁷ Department of Pathology, General Hospital Graz West; ⁸ Department of Internal Medicine, Medical University of Graz, Graz, Austria; Departments of ⁹ Pathology and ¹⁰ Internal Medicine III, General Hospital Salzburg, Paracelsus Private Medical University, Salzburg, Austria; and ¹¹ Institute of Pathology and ¹² Department of Surgery, General Hospital Wiener Neustadt, Wiener Neustadt, Austria

Requests for reprints: Martin Filipits, Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. Phone: 43-1-4277-65237; Fax: 43-1-4277-65196; E-mail: martin.filipits{at}meduniwien.ac.at.

Purpose: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor–positive breast cancer patients who were treated with tamoxifen-based therapy.

Experimental Design: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors.

Results: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1–positive tumors compared with patients with cyclin D1–negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1–positive tumors than in patients with cyclin D1–negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005].

Conclusion: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor–positive breast cancer who received adjuvant tamoxifen-based therapy.