title: Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole.
abstract: Estrogen synthesis suppression induced by aromatase inhibitors in breast cancer (BC) patients may be affected by single nucleotide polymorphisms (SNPs) of the gene encoding aromatase enzyme, CYP19A1. We assessed the association between plasma estrone sulfate (ES), letrozole treatment, and four SNPs of CYP19A1 gene (rs10046 C>T, rs4646 G>T, rs749292 C>T, rs727479 T>G) which seem to be related to circulating estrogen levels. Patients were enrolled into a prospective, Italian multi-center clinical trial (Gruppo Italiano Mammella, GIM-5) testing the association of CYP19A1 SNPs with the efficacy of letrozole adjuvant therapy, in postmenopausal early BC patients. SNPs were identified from peripheral blood cell DNA. Plasma ES concentrations were evaluated by Radio Immuno Assay. Blood samples were obtained immediately before letrozole therapy (N = 204), at 6-weeks (N = 178), 6 (N = 152) and 12-months (N = 136) during treatment. Medians (IQR) of ES were 160 pg/mL (85-274) at baseline, 35 pg/mL (12-64) at 6-weeks, 29 pg/mL (17-48) at 6 months and 25 pg/mL (8-46) after 12 months treatment. No statistically significant association was evident between polymorphisms and ES circulating levels during letrozole therapy. Letrozole suppression of the aromatase enzyme function is not affected by polymorphisms of CYP19A1 gene in postmenopausal BC patients.
authors.affiliation: Oncology Unit, Ospedale Sacro Cuore Don Calabria, Via Sempreboni, 5, 37024 Negrar, VR, Italy. gianluigi.lunardi@sacrocuore.it
authors.forename: G
authors.initials: G
authors.lastname: Lunardi
authors.forename: P
authors.initials: P
authors.lastname: Piccioli
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: R
authors.initials: R
authors.lastname: Notaro
authors.forename: S
authors.initials: S
authors.lastname: Lastraioli
authors.forename: M
authors.initials: M
authors.lastname: Serra
authors.forename: P
authors.initials: P
authors.lastname: Marroni
authors.forename: C
authors.initials: C
authors.lastname: Bighin
authors.forename: M
authors.initials: M
authors.lastname: Mansutti
authors.forename: F
authors.initials: F
authors.lastname: Puglisi
authors.forename: M
authors.initials: M
authors.lastname: Porpiglia
authors.forename: R
authors.initials: R
authors.lastname: Ponzone
authors.forename: G
authors.initials: G
authors.lastname: Bisagni
authors.forename: O
authors.initials: O
authors.lastname: Garrone
authors.forename: G
authors.initials: G
authors.lastname: Cavazzini
authors.forename: M
authors.initials: M
authors.lastname: Clavarezza
authors.forename: L
authors.initials: L
authors.lastname: Del Mastro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001141:Aromatase / Q000235:genetics*; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D002986:Clinical Trials as Topic; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011446:Prospective Studies; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077289:Letrozole; D001141:Aromatase; C561410:CYP19A1 protein, human; C017296:estrone sulfate