Abstract
Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-β-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC) and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049). The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007). This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole.
Highlights
Breast cancer is one of the most prevalent malignancies in women worldwide
We found that the rs4646 variant of the CYP19A1 gene is associated with greater efficacy of anastrozole administered in postmenopausal women with metastatic breast carcinoma (MBC) and retained statistical significance after Bonferroni correction
The present study demonstrates that an association between clinical outcome of anastrozole therapy and genetic variant are biologically plausible for the following reasons
Summary
Breast cancer is one of the most prevalent malignancies in women worldwide. In 2012, 226,870 women were diagnosed with breast cancer in the United States, and nearly three million people are estimated to be living in the United States with a history of invasive breast cancer [1]. Aromatase inhibitors (AIs) are used in the treatment of metastatic breast cancer [3,4] and in the adjuvant setting [5,6,7]. Two thirds of breast cancer cases express estrogen (ER) and/or progesterone receptors (PgR) [12,13,14]; positivity of estrogen or progesterone receptors in breast cancer has been related to the efficacy of tamoxifen, as well as AIs. To date, only the presence and intensity of hormonal receptors (ER/PgR) are useful tools as predictive markers in clinical practice.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
