Association of the polymorphisms CYP19 (TTTA)n in treatment response to hormone therapy based in aromatase inhibitors in breast cancer patients.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3033 Background Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first study in Mexican women examining associations between female with breast cancer and polymorphisms CYP19 (TTTA repeated polymorphism). Methods We conducted a study among 180 healthy women and 70 women with breast cancer underwent hormone therapy with aromatase inhibitor. DNA and questionnaire data was obtained. Tandem repeated (TTTA)n polymorphism in CYP19 gene was determined by PCR followed by electrophoresis on denaturalizing acrilamide gel stained with silver nitrate. Differences were visualized with Gel-Doc BioRad. Estrone, estradiol and FSH levels were measured by RIA and IRMA. We used likelihood-based statistical methods to examine allelic associations. Results: 250 women (age 55 ± 12 years) were included. BMI was 30 ± 7.1 Kg/m2. We found a distribution of different CYP19 allele frequencies. In healthy women the allele frequencies with 6 (32.7 %) and 7 (21.6 %) tandem repetitions were the most frequent, in women with breast cancer the alleles with 6(29%) and 10(26%) tandem repeated were the most frequent. A relationship between hormonal levels and number of (TTTA) repeated was not found. Anastrozol reduced significantly estrona and estradiol. Surpriseling we found in a patients with 10 or more (TTTA)n repeated an association with a mayor tumoral activity (p=0.04). Conclusion This study indicates that status of CYP19 >10 TTTA repeated might be related to increased breast cancer risk and with the clinical response (aromatase inhibitor). Because of this is the first study to report an association between CYP19 >10 TTTA repeated and treatment hormonal response in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3033.