A recombinant cell bioassay for measurement of overall estrogenic activity of serum: preliminary results in women with breast cancer.
The estrogenic status of patients with breast cancer may influence the prognosis and the response to treatment and is currently assessed by immunological measurement of serum estradiol. This does not account for estrogenic or anti-estrogenic activity related to growth factors able to activate the estrogen receptor, to anti-estrogenic drugs or to exogenous supply of estrogen-like compounds. We developed a recombinant bioassay based on a mammary cell line expressing luciferase in an estrogen receptor-dependent way. In a human serum matrix the MELN system was able to detect the transcriptional activity of estradiol, growth factors (epidermal growth factor (EGF), insulin at insulin-like growth factor 1 (IGF-1)-like concentrations), xeno-estrogens (diethylstilbestrol, phytoestrogens) and tamoxifen in a dose-dependent manner. The intra- and inter-assay variations were < 6% and < or = 15%, respectively, whatever the estradiol concentration; the functional sensitivity was < 10 pmol/l equivalents of estradiol. We assessed the overall estrogenic activity of serum (OEAS) in 16 healthy women and in 24 women with advanced breast cancer. The correlation between OEAS and serum log10 17-beta-estradiol (E2) was good for healthy women (r2=0.8568) but poor for patients (r2=0.0563). Assessment of the OEAS/E2 ratio as a prognostic and predictive factor would be of interest in clinical prospective trials involving ER+ breast cancer patients.
Séronie-Vivien
Sophie
S
Inserm U563, Centre de Physiopathologie de Toulouse Purpan, Département Innovation Thérapeutique et Oncologie Moléculaire, Institut Claudius Regaud, Toulouse, France. seronie@icr.fnclcc.fr
Dalenc
Florence
F
Balaguer
Patrick
P
Nicolas
Jean-Claude
JC
Roché
Henri
H
Faye
Jean-Charles
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay / Q000379:methods*; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D004967:Estrogens / Q000032:analysis / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008156:Luciferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013002:Somatomedins / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D004967:Estrogens; D011960:Receptors, Estrogen; D013002:Somatomedins; D013629:Tamoxifen; D004958:Estradiol; D008156:Luciferases