title: Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients.
abstract: Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.
authors.affiliation: Service d'Oncologie Radiothérapie, Hôpital Tenon, AP-HP, Cancerest, GHU EST, Université Paris VI, 4 rue de la Chine, Paris 75020, France. moureau@marseille.fnclcc.fr
authors.forename: L
authors.initials: L
authors.lastname: Moureau-Zabotto
authors.forename: S
authors.initials: S
authors.lastname: Ricci
authors.forename: J P
authors.initials: JP
authors.lastname: Lefranc
authors.forename: F
authors.initials: F
authors.lastname: Coulet
authors.forename: C
authors.initials: C
authors.lastname: Genestie
authors.forename: M
authors.initials: M
authors.lastname: Antoine
authors.forename: S
authors.initials: S
authors.lastname: Uzan
authors.forename: J P
authors.initials: JP
authors.lastname: Lotz
authors.forename: E
authors.initials: E
authors.lastname: Touboul
authors.forename: R
authors.initials: R
authors.lastname: Lacave
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D019450:Genes, MDR; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics; D015999:Multivariate Analysis; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051549:Glutathione S-Transferase pi; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C496556:GSTP1 protein, human; C421109:multidrug resistance-associated protein 1