title: Plasminogen activator inhibitor-1 (PAI-1) is not related to response to neoadjuvant chemotherapy in breast cancer.
abstract: There is no information available on the relation between response to chemotherapy and the high-risk phenotype assessed by uPA and/or PAI-1. The clinical situation of neoadjuvant chemotherapy provides a means of rapidly assessing the sensitivity of the primary tumour to cytotoxic drug regimens. The goal of the study was to assess prospectively the predictive value of PAI-1 for response to first-line chemotherapy. PAI-1 concentration was measured on hypertonic cytosolic extracts (0.4 M potassium chloride) by ELISA before chemotherapy on a drill biopsy sample of the tumour in 69 T2 and T3 breast cancer patients (median age 46 years). Oestrogen receptor (ER) (51% ER+), progesterone receptor (PR) (58% PR+), S-phase (median 4.0%) and ploidy were also assessed in the majority of cases. The clinical response to treatment was evaluated after four cycles of FAC or FEC regimen (5-fluorouracil, epidoxorubicin or doxorubicin and cyclophosphamide) (one cycle every 4th week). PAI-1 could be assayed in 29 post-chemotherapy surgical samples. The objective response rate (complete response plus partial response) was 59% (41 out of 69). PAI-1 expressed as gram of tissue (range 19-2370 ng g(-1) tissue) was highly correlated (r = 0.98) to PAI-1 expressed as mg protein (range 0.5-68 ng mg(-1) protein). No correlation between PAI-1 level and response could be observed, with any cut-off. The post- and pre-chemotherapy PAI-1 levels were correlated (r = 0.66). Of all biological parameters, only high S-phase (cut-off 5%) was slightly correlated (chi2 = 3.91, P = 0.05) to response. These data suggest that PAI-1 is not a predictive marker of response to chemotherapy in breast cancer and that its level is not altered by neoadjuvant chemotherapy.
authors.affiliation: Physiopathology Laboratory and Medical Oncology Department, Institute Curie, Paris, France.
authors.forename: J Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: C
authors.initials: C
authors.lastname: Lainé-Bidron
authors.forename: P
authors.initials: P
authors.lastname: Beuzeboc
authors.forename: P
authors.initials: P
authors.lastname: De Crémoux
authors.forename: P
authors.initials: P
authors.lastname: Pouillart
authors.forename: H
authors.initials: H
authors.lastname: Magdelénat
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*
chemical_list: D017395:Plasminogen Activator Inhibitor 1