title: The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas.
abstract: Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospective series of 202 patients with stage T1a,b invasive breast carcinomas was evaluated. The clinicopathological features (age, histological grade, extensive in situ carcinoma, hormone receptor status, and nodal metastasis) as well as microvessel density and the expression of c-erb-B2, p53, MIB-1/Ki-67, and cdc25B were assessed. In addition, expression of the cell cycle inhibitor p27 was evaluated. Nineteen patients (18% of patients who had axillary dissection) had locoregional lymph node metastases. Forty-two % of them died of disease (median survival, 112 months), whereas mortality was 11% in node-negative patients (median survival, 168 months; P = 0.0055). Patients with low p27 expression had a median survival of 139 months (17% mortality) versus 174 months (9% mortality) in the group with high p27 expression (P = 0.0233). Lack of p27 was associated with poor prognosis when node-positive patients were excluded (P = 0.0252). Nodal status and low p27 were found to be the only independent prognostic parameters by both univariate and multivariate analysis, with relative risks of dying of disease of 4.9 (P = 0.001) and 3.4 (P = 0.0306), respectively. Assessment of p27, which yields prognostic information in node-negative patients, could be useful to identify patients with small, invasive breast carcinomas who might benefit from adjuvant therapy.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: P
authors.initials: P
authors.lastname: Tan
authors.forename: B
authors.initials: B
authors.lastname: Cady
authors.forename: M
authors.initials: M
authors.lastname: Wanner
authors.forename: P
authors.initials: P
authors.lastname: Worland
authors.forename: B
authors.initials: B
authors.lastname: Cukor
authors.forename: C
authors.initials: C
authors.lastname: Magi-Galluzzi
authors.forename: P
authors.initials: P
authors.lastname: Lavin
authors.forename: G
authors.initials: G
authors.lastname: Draetta
authors.forename: M
authors.initials: M
authors.lastname: Pagano
authors.forename: M
authors.initials: M
authors.lastname: Loda
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D018797:Cell Cycle Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D010749:Phosphoprotein Phosphatases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases