Annals of Oncology Advance Access published online on February 13, 2008
Annals of Oncology, doi:10.1093/annonc/mdm547
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p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer
1 Department of Oncology, Ospedale Infermi, Rimini and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (FC) Italy
2 International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA, USA
3 Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy
4 Department of Oncology, Ospedale San Giovanni, Bellinzona, Switzerland
5 International Breast Cancer Study Group Coordinating Center, Bern, Switzerland
6 European Institute of Oncology, Milan, Italy and Oncology Institute of Southern Switzerland, Lugano, Switzerland
7 University of Sydney, Sydney, New South Wales, Australia
8 International Breast Cancer Study Group Statistical Center and Frontier Science and Technology Research Foundation, Boston, MA, USA
9 Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, UK
10 Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan, Milan, Italy
* Correspondence to: Dr Alberto Ravaioli, Department of Oncology, Ospedale Infermi, Rimini and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (FC), Italy Tel: +390541705014; Fax: +390541705567; E-mail: aravaiol{at}auslrn.net
Background: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer.
Patients and methods: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients.
Results: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2.
Conclusions: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.
breast cancer, chemotherapy, hormonal therapy, p27, Skp2
Received for publication September 17, 2007. Accepted for publication October 30, 2007.
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  M. Filipits, M. Rudas, H. Heinzl, R. Jakesz, E. Kubista, S. Lax, W. Schippinger, O. Dietze, R. Greil, W. Stiglbauer, et al. Low p27 Expression Predicts Early Relapse and Death in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients Receiving Adjuvant Tamoxifen Therapy Clin. Cancer Res., September 15, 2009; 15(18): 5888 - 5894. [Abstract] [Full Text] [PDF]
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