Literature DB >> 12655514

Decreased immunoreactivity for p27 protein in patients with early-stage breast carcinoma is correlated with HER-2/neu overexpression and with benefit from one course of perioperative chemotherapy in patients with negative lymph node status: results from International Breast Cancer Study Group Trial V.

Vito J Spataro1, Heather Litman, Giuseppe Viale, Fausto Maffini, Michele Masullo, Rastko Golouh, Francisco J Martinez-Tello, Piergioranni Grigolato, Keith B Shilkin, Barry A Gusterson, Monica Castiglione-Gertsch, Karen Price, Jurii Lindtner, Hernan Cortés-Funes, Edda Simoncini, Michael J Byrne, John Collins, Richard D Gelber, Alan S Coates, Aron Goldhirsch.   

Abstract

BACKGROUND: The objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin-dependent kinase inhibitor p27(Kip1) in patients with early-stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers.
METHODS: Immunoreactivity for p27 protein was analyzed on tumor slides from 461 patients who were enrolled in the International Breast Cancer Study Group (IBCSG) Trial V (median follow-up, 13 years), including 198 patients with lymph node negative disease and 263 patients with lymph node positive disease. Tumors with < 50% immunoreactive neoplastic cells were considered low expressors. Immunoreactivity for p27 was correlated with several clinicopathologic characteristics. Disease free survival (DFS) and overall survival were analyzed according to p27 immunoreactivity and treatment group.
RESULTS: In the lymph node negative population, decreased p27 immunoreactivity was associated with higher tumor grade (P = 0.001) and HER-2/neu overexpression (P = 0.04). In the lymph node positive population, low p27 expression was associated with higher tumor grade (P = 0.01), low expression of thymidylate synthase (P = 0.001), and higher Ki-67 expression (P = 0.007). DFS was not significantly different according to p27 status in either lymph node negative patients (10-year DFS: low p27 expression, 53% +/- 5%; high p27 expression, 55% +/- 5%) or in lymph node positive patients (10 year DFS: low p27 expression, 33% +/- 4%; high p27 expression, 32% +/- 4%). However, in the lymph node negative population, the benefit of one course of perioperative chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil was confined exclusively to patients with tumors that showed reduced p27 immunoreactivity (P = 0.03; test for interaction).
CONCLUSIONS: This analysis indicates that p27 immunoreactivity has little if any prognostic value in patients with early-stage breast carcinoma. However, these findings suggest that, in patients with breast carcinoma who have negative lymph node status, reduced p27 immunoreactivity is associated with HER-2/neu overexpression and may be predictive of a benefit from the early administration of adjuvant chemotherapy. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11224

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Year:  2003        PMID: 12655514     DOI: 10.1002/cncr.11224

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  13 in total

1.  p27(Kip1) and cyclin E expression and breast cancer survival after treatment with adjuvant chemotherapy.

Authors:  Peggy L Porter; William E Barlow; I-Tien Yeh; Ming Gang Lin; Xiaopu P Yuan; Elizabeth Donato; George W Sledge; Charles L Shapiro; James N Ingle; Charles M Haskell; Kathy S Albain; James M Roberts; Robert B Livingston; Daniel F Hayes
Journal:  J Natl Cancer Inst       Date:  2006-12-06       Impact factor: 13.506

2.  A study to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.

Authors:  Komala Pillay; Heather McCleod; Runjan Chetty; Pauline Hall
Journal:  World J Surg Oncol       Date:  2011-03-16       Impact factor: 2.754

3.  Hunk is required for HER2/neu-induced mammary tumorigenesis.

Authors:  Elizabeth S Yeh; Thomas W Yang; Jason J Jung; Heather P Gardner; Robert D Cardiff; Lewis A Chodosh
Journal:  J Clin Invest       Date:  2011-03       Impact factor: 14.808

Review 4.  Role of the CDK inhibitor p27 (Kip1) in mammary development and carcinogenesis: insights from knockout mice.

Authors:  Elizabeth A Musgrove; Elizabeth A Davison; Christopher J Ormandy
Journal:  J Mammary Gland Biol Neoplasia       Date:  2004-01       Impact factor: 2.673

Review 5.  p27 deregulation in breast cancer: prognostic significance and implications for therapy.

Authors:  A Alkarain; R Jordan; J Slingerland
Journal:  J Mammary Gland Biol Neoplasia       Date:  2004-01       Impact factor: 2.673

Review 6.  The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis.

Authors:  M M Moasser
Journal:  Oncogene       Date:  2007-04-30       Impact factor: 9.867

7.  Prognostic value of p27 kip1 expression in adenocarcinoma of the pancreatic head region.

Authors:  Jerzy Mielko; Wojciech P Polkowski; Danuta G Skomra; Andrzej J Stanisławek; Andrzej M Kurylcio; Elzbieta M Korobowicz
Journal:  HPB (Oxford)       Date:  2006       Impact factor: 3.647

Review 8.  Measuring proliferation in breast cancer: practicalities and applications.

Authors:  Mark J Beresford; George D Wilson; Andreas Makris
Journal:  Breast Cancer Res       Date:  2006       Impact factor: 6.466

Review 9.  Deregulation of p27 by oncogenic signaling and its prognostic significance in breast cancer.

Authors:  Angel Alkarain; Joyce Slingerland
Journal:  Breast Cancer Res       Date:  2003-10-21       Impact factor: 6.466

Review 10.  Genetic Association Between CDKN1B rs2066827 Polymorphism and Susceptibility to Cancer.

Authors:  Yongchao Lu; Kejian Gao; Miao Zhang; Aiyan Zhou; Xiaoming Zhou; Zhongan Guan; Xuewen Shi; Shujian Ge
Journal:  Medicine (Baltimore)       Date:  2015-11       Impact factor: 1.817

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