Excretion of estrogens, catecholestrogens and phytoestrogens in carriers of BRCA1 gene mutations: effects of metformin.
BRCA1 gene mutation is associated with a combination of excessive aromatase activity/expression, predominantly estrogen receptor-negative phenotypes of tumors, and only scarce information about estrogen contents in body fluids. In the present work, isotope dilution capillary gas chromatography/mass spectrometry was used to study urinary excretion of estrogens, their catechol metabolites, and phytoestrogens in 22 women (11 with BCRA1 gene mutations and 11 without these mutations) in average 5.1+/-0.4 years before surgery for breast cancer. BCRA1 mutation carriers (including 3 premenopausal females) compared with respective controls showed significantly higher urinary estradiol and estrone excretion and a trend to an increased 2-OH-E2 excretion. In the subgroup of untreated postmenopausal women, BCRA1 mutation carriers showed a trend to increased estradiol and estrone excretion and to a higher value of the mean levels of all estrogen metabolites tested. The treatment after the baseline laboratory investigation of 6 women from postmenopausal group with the antidiabetic biguanide metformin for 3 months was associated with decreases in the excretion rates of 4-hydroxyestradiol, 2-methoxyestradiol, and 16-epiestriol and did not influence phytoestrogen excretion. The decrease in 2-methoxyestrogen excretion was more consistent in women without BCRA1 mutations than in BCRA1 mutation carriers. The data suggest the possibility that aromatase complex activation in BCRA1 mutation carriers is combined with increases in both, estrogen metabolism into catecholestrogens and their inactivation by methoxylation, and that metformin may affect both of these pathways.
Berstein
L M
LM
N.N. Petrov Research Insititute of Oncology, St. Petersburg, Russia. levmb@endocrin.spb.ru
Koskela
A
A
Boyarkina
M P
MP
Adlercreutz
H
H
D001943:Breast Neoplasms / Q000235:genetics / Q000652:urine*; D004967:Estrogens / Q000652:urine*; D002393:Estrogens, Catechol / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D048789:Phytoestrogens / Q000652:urine*; D010865:Pilot Projects; D017698:Postmenopause / Q000187:drug effects; D011379:Prognosis
D004967:Estrogens; D002393:Estrogens, Catechol; D007004:Hypoglycemic Agents; D048789:Phytoestrogens; D008687:Metformin