title: The role of cathepsin D and PAI-1 in primary invasive breast cancer as prognosticators and predictors of treatment benefit with adjuvant tamoxifen.
abstract: In the last few years there has been an increased interest in treatment predictive factors in breast cancer patients. The aim of the study was to analyse the role of cathepsin D and plasminogen activator inhibitor-1 (PAI-1) expression as independent prognosticators and to assess their predictive value with respect to tamoxifen treatment. This study comprises 1851 patients with primary breast cancer diagnosed during 1988-1992. Their median age was 62 years (range: 24-91). The end-point was distant disease recurrence-free interval. Adjuvant treatment with tamoxifen was given to 1136 patients (61%). The median follow-up time was 59 months (range: 39-88). Cathepsin D content was shown to be a significant independent prognosticator in multivariate Cox analysis (P=0.02). The optimal cut-off level was 10 fmol/mg protein, other cut-off levels did not improve the results. The level of cathepsin D also appeared to predict the benefit of tamoxifen among oestrogen receptor (ER)-positive patients although this result did not reach statistical significance (P=0.09). In a multivariate Cox analysis including 497 patients PAI-1 content was shown to be a significant independent prognosticator (P=0.003) but did not appear to predict the benefit of tamoxifen treatment. The optimal cut-off level appeared to be 3 ng/mg protein, which was close to the median value 2.5 ng/mg (range: 0-51). We conclude that cathepsin D is a significant independent prognosticator and may possibly also predict the benefit of tamoxifen amongst ER-positive patients. PAI-1 was also found to be a strong independent prognosticator but no treatment interaction with adjuvant tamoxifen was found.
authors.affiliation: Department of Oncology and Pathology, Oncologic Center, Radiumhemmet, Karolinska Hospital, S 171 76, Stockholm, Sweden. a.billgren@telia.com
authors.forename: A M
authors.initials: AM
authors.lastname: Billgren
authors.forename: L E
authors.initials: LE
authors.lastname: Rutqvist
authors.forename: H
authors.initials: H
authors.lastname: Johansson
authors.forename: T
authors.initials: T
authors.lastname: Hägerström
authors.forename: L
authors.initials: L
authors.lastname: Skoog
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D002402:Cathepsin D / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D015411:Mastectomy, Modified Radical / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D013629:Tamoxifen; D002402:Cathepsin D