Clinical Study

British Journal of Cancer (2006) 94, 473–480. doi:10.1038/sj.bjc.6602958 www.bjcancer.com
Published online 24 January 2006

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

L Moureau-Zabotto1,8, S Ricci2, J P Lefranc3, F Coulet2,9, C Genestie4, M Antoine5, S Uzan6, J P Lotz7, E Touboul1 and R Lacave2

  1. 1Service d'Oncologie Radiothérapie, Hôpital Tenon, AP-HP, Cancerest, GHU EST, Université Paris VI, 4 rue de la Chine, Paris 75020, France
  2. 2Service d'Histologie-Biologie tumorale, Hôpital Tenon, AP-HP, Cancerest, GHU EST, Université Paris VI, 4 rue de la Chine, Paris 75020, France
  3. 3Service de Chirurgie Mammaire et Gynécologique, Groupe Hospitalier Pitié Salpêtrière, AP-HP, GHU EST, 47-83 Boulevard de l'hôpital, Paris 75013, France
  4. 4Service d'Anatomopathologie, Groupe Hospitalier Pitié Salpêtrière, AP-HP, GHU EST, 47-83 Boulevard de l'hôpital, Paris 75013, France
  5. 5Service d'Anatomopathologie, Hôpital Tenon, AP-HP, Cancerest, GHU EST, Université Paris VI, 4 rue de la Chine, Paris 75020, France
  6. 6Service de Gynécologie Obstétrique, Hôpital Tenon, AP-HP, Cancerest, GHU EST, Université Paris VI, 4 rue de la Chine, Paris 75020, France
  7. 7Service d'Oncologie Médicale, Hôpital Tenon, AP-HP, Cancerest, GHU EST, Université Paris VI, 4 rue de la Chine, Paris 75020, France

Correspondence: Dr L Moureau-Zabotto, E-mails: moureaul@marseille.fnclcc.fr or laurence.moureau.zabotto@tiscali.fr

8Current address: Service de Radiothérapie, Institut Paoli Calmettes, 232 boulevard de Sainte Marguerite, Marseille 13009, France

9Current address: Laboratoire d'Onco-Angio-Génétique, Fédération de Génétique, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, GHU EST, 47-83 Boulevard de l'hôpital, 75013 Paris, France

Received 15 September 2005; Revised 13 December 2005; Accepted 13 December 2005; Published online 24 January 2006.

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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 chemotherapyplusminusradiotherapyplusminushormonal 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 greater than or equal to5 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.

Keywords:

MDR1, MRP1, GSTP1, rt–PCR, breast cancer, prognosis