title: Prolonged tamoxifen treatment increases relapse-free survival for patients with primary breast cancer expressing high levels of VEGF.
abstract: Previous retrospective studies have shown that high intratumoural levels of vascular endothelial growth factor (VEGF) correlate with an inferior outcome for patients treated with adjuvant tamoxifen. Our objectives were to validate the impact of VEGF on survival after adjuvant tamoxifen and to investigate the interaction between VEGF and treatment duration. For this purpose tumour homogenates from 402 patients with operable oestrogen receptor positive breast cancer (BC), treated with tamoxifen for 2 (n=149) or 5 years (n=253) as the only systemic adjuvant therapy were included. The median follow-up time for surviving patients was 9.8 years (range 0.5-14.8 years). Expression of VEGF was assessed by an enzyme-linked immunosorbent assay and investigated in relation to the standard BC parameters and survival. In the total population, higher VEGF was significantly correlated with shorter recurrence-free survival (RFS) (HR=1.63, 95%CI=1.11-2.39, p=0.010), breast cancer corrected survival (BCCS) (HR=1.82, 95%CI=1.13-2.93, p=0.014) and overall survival (OS) (HR=1.51, 95%CI=1.11-2.05, p=0.009). High VEGF was significantly associated with reduced RFS (HR=2.61, 95%CI=1.45-4.70, p=0.001) after two years of tamoxifen, whilst no difference was seen in patients treated for five years (HR=1.09, 95%CI=0.64-1.84, p=0.760). A statistically significant interaction was observed between high VEGF expression and improved RFS after 5-year tamoxifen (p=0.034). In concordance with previous studies, high VEGF was significantly correlated with shorter survival. We present data not reported previously revealing that patients expressing high levels of VEGF display a better outcome provided that tamoxifen is given for five years. Further studies on the impact of VEGF on a 5-year regimen are motivated.
authors.affiliation: Karolinska Biomics Center, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: B C
authors.initials: BC
authors.lastname: Sanchez
authors.forename: M
authors.initials: M
authors.lastname: Sundqvist
authors.forename: H
authors.initials: H
authors.lastname: Fohlin
authors.forename: F
authors.initials: F
authors.lastname: Spyratos
authors.forename: B
authors.initials: B
authors.lastname: Nordenskjöld
authors.forename: O
authors.initials: O
authors.lastname: Stål
authors.forename: B K
authors.initials: BK
authors.lastname: Linderholm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015409:Mastectomy, Radical / Q000401:mortality; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen