title: Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy.
abstract: Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p2lWaf1, p27KiP1, p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21Waf1, p27Kip1, p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21Waf1, p27Kip1, p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.
authors.affiliation: Department of Internal Medicine 1, Division of Oncology, University Hospital, Vienna, Austria.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Pohl
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Susanne
authors.initials: S
authors.lastname: Taucher
authors.forename: Thomas
authors.initials: T
authors.lastname: Stranzl
authors.forename: Günther G
authors.initials: GG
authors.lastname: Steger
authors.forename: Raimund
authors.initials: R
authors.lastname: Jakesz
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics; D017024:Chemotherapy, Adjuvant / Q000379:methods; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000187:drug effects / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000187:drug effects / Q000235:genetics; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011300:Preoperative Care; D011987:Receptors, Steroid / Q000187:drug effects; D043823:Taxoids; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000235:genetics
chemical_list: C534696:CCND3 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D011987:Receptors, Steroid; D043823:Taxoids; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate