High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer.
Variants of survivin with differing subcellular localizations might mediate the different functions of survivin, i.e. cell-cycle regulation and apoptosis inhibition. Highly proliferative tumors are more sensitive to chemotherapy, whereas apoptosis resistant cells would be refractory to endocrine therapy. Possibly, this explains incongruent data on the association of survivin with prognosis in breast cancer. Survivin levels were measured using ELISA in 800 x g pellets and 100,000 x g supernatants of breast cancer tissues from patients that were treated with either chemotherapy or endocrine therapy for advanced disease. These fractions might be enriched with nuclear or cytoplasmatic located survivin variants. Survivin levels were associated with tumors with poor prognostic clinical characteristics. For the patients treated with endocrine therapy, the patients with high survivin levels exhibited a significantly shorter progression free survival (PFS) than those who had low levels (pellet survivin Hazard Ratio (HR)=2.74, 95% Confidence Interval (CI)=1.31-5.72, p=0.008 and median PFS 5.8 versus 8.6 months, p=0.006, log-rank; cytosolic survivin HR=3.03, 95% CI=1.45-6.35, p=0.003). In contrast, for patients treated with chemotherapy, those with high cytosolic survivin had a significantly longer PFS than those with low levels (median PFS of 6.2 months, versus 4.7 months for patients with low cytosolic concentrations, p=0.024, log-rank). Thus, high levels of survivin are mainly related with a poor response to endocrine therapy, but a good response to chemotherapy. This phenomenon might be related to the different functions of survivin.
Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. p.span@ace.umcn.nl
Paul N
PN
Span
Vivianne C G
VC
Tjan-Heijnen
Peggy
P
Manders
Doorlene
D
van Tienoven
Jeffrey
J
Lehr
Fred C G J
FC
Sweep
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D000077022:Survivin; D013629:Tamoxifen / Q000627:therapeutic use
D047072:Aromatase Inhibitors; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D013629:Tamoxifen; D017258:Medroxyprogesterone Acetate