title: Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer.
abstract: We wanted to study cyclin A as a marker for prognosis and chemotherapy response. A total of 283 women with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel to sequential methotrexate-fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin-embedded blocks of the primary tumour were available for 96 patients (34%). The proportion of cells expressing cyclin A was determined by immunohistochemistry using a mouse monoclonal antibody to human cyclin A. Response evaluation was performed according to WHO recommendations. The median cyclin A positivity of tumour cells was 14.5% (range 1.2-45.0). Cyclin A correlated statistically significantly to all other tested proliferation markers (mitotic count, histological grade and Ki-67). A high cyclin A correlated significantly to a shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24-3.03) and survival from diagnosis, RR 2.49 (95% CI 1.45-4.29), cutoff point for high/low proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or survival after anthracycline, docetaxel or MF therapy. Of all tumour biological factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to have the strongest prognostic value. Cyclin A is a good marker for tumour proliferation and prognosis in breast cancer. In the present study, cyclin A did not predict chemotherapy response.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, PO Box 180, 00029 HUS Helsinki, Finland. Paula.Poikonen@hus.fi
authors.forename: P
authors.initials: P
authors.lastname: Poikonen
authors.forename: J
authors.initials: J
authors.lastname: Sjöström
authors.forename: R-M
authors.initials: RM
authors.lastname: Amini
authors.forename: K
authors.initials: K
authors.lastname: Villman
authors.forename: J
authors.initials: J
authors.lastname: Ahlgren
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D044584:Carcinoma, Ductal / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D008727:Methotrexate / Q000008:administration & dosage; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D019925:Cyclin A; D005472:Fluorouracil; D008727:Methotrexate