Low p27 Expression Predicts Early Relapse and Death in Postmenopausal Hormone Receptor–Positive Breast Cancer Patients Receiving Adjuvant Tamoxifen Therapy

Abstract

Purpose: Previously, we have shown that p27 may be a potential predictive biomarker for the selection of premenopausal women with early-stage hormone-responsive breast cancer for adjuvant endocrine therapy. The purpose of the present study was to assess the clinical relevance of p27 expression in postmenopausal hormone receptor-positive breast cancer patients who were treated with adjuvant tamoxifen therapy. Experimental Design: We determined the expression of p27 by immunohistochemistry in the surgical specimens of breast carcinoma patients who had been enrolled in Austrian Breast and Colorectal Cancer Study Group Trial 06 and received tamoxifen for 5 years. Early relapse and death within the first 5 years of follow-up were analyzed using Cox models adjusted for clinical and pathologic factors. Results: p27 expression was high (>70% p27-positive tumor cells) in 252 of 483 (52%) tumor specimens and was associated with favorable outcome of the patients. Women with high p27 expression had a significantly longer disease-free survival (adjusted hazard ratio for relapse, 0.22; 95% confidence interval, 0.11-0.42; P < 0.001) and overall survival (adjusted hazard ratio for death, 0.39; 95% confidence interval, 0.21-0.72; P = 0.002) as compared with women with low p27 expression. Conclusion: Low p27 expression independently predicts early relapse and death in postmenopausal women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen for 5 years. (Clin Cancer Res 2009;15(18):5888-94)

PPM1H Is a p27 Phosphatase Implicated in Trastuzumab Resistance

“…Based on the mechanism of PPM1H, this trend is consistent with many studies in the literature that have established low p27 expression and high SKP2 expression as poor prognostic indicators in breast cancer (26,(37)(38)(39)(40)(41)(42)(43)(44). Furthermore, the cell-cycle inhibitory activity of p27 on cyclin E/CDK2 complexes can be abrogated by cyclin D/CDK4, which binds p27 and titrates it away from cyclin E/CDK2.…”

In vivo and in vitro demonstration of herb-drug interference in human breast cancer cells treated with tamoxifen and trastuzumab

“…27,28 Recent studies have demonstrated that p27(Kip1) is a predictive factor for Tam treatment response in premenopausal and postmenopausal women with breast cancer. 29,30 In contrast to other tumor suppressor proteins, p27 expression levels in tumor cells are frequently regulated by ubiquitin-dependent proteolysis, which is controlled by the phosphorylation of p27 at a conserved threonine (T187) and facilitates polyubiquitylation of p27; this prevents binding to its critical cellular targets such as the cyclin E/Cdk2 and A/Cdk2 complexes. In addition, the phosphorylation of p27 by AKT and SRC kinases at either T157 (AKT) or tyrosine 74/88 (SRC) induces cellular mislocalization or functional inactivation, which disables p27 as a tumor suppressor protein.…”

Validation of p27KIP1 expression levels as a candidate predictive biomarker of response to rapalogs in patient-derived breast tumor xenografts

“…P27kip1 is a well-known tumor suppressor gene, its expression levels have both prognostic and therapeutic implications [13][14][15][16][17][18]. In this study, we intend to validate p27KIP1 expression levels as a predictive marker for the response of rapalogs based on primary breast cancer cells and patientderived breast tumor xenograft models.…”