The combination of these two polymorphisms was found to be more useful in the assessment of the ER-positive breast cancer risk (OR=3.00, 95% CI=1.56-5.74) than the CYP19 (TTTA)7(-3bp) polymorphism alone.
Our laboratory has also evaluated the growth-inhibiting activity of aromatase inhibitors in estrogen receptor-positive breast cancer using three-dimensional cell cultures of aromatase-over expressing MCF-7 and T-47D cell lines (i.e.MCF-7aro and T-47Daro).
Aromatase is the enzyme responsible for the conversion of androgens into estrogens, and synthetic aromatase inhibitors such as letrozole, anastrozole, and exemestane have proven to be effective endocrine regimens for ER-positive breast cancer.
Currently, the standard of care for estrogen receptor (ER)-positive breast cancer is 5 years of tamoxifen (TAM) or an aromatase inhibitor (AI) such as anastrozole.
In this model, tumors of human estrogen receptor (ER) positive breast cancer cells stably transfected with aromatase (Ac-1) are grown in immune-compromised mice.
Adjuvant endocrine treatment with aromatase inhibitors improves disease-free survival compared with tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer.
Our study demonstrated genetic polymorphisms of ERalpha, CYP19A1, COMT and p53 genes frequently occur in ER-positive breast cancer in premenopausal Japanese women.
Estrogen deprivation using aromatase inhibitors is one of the standard treatments for postmenopausal women with estrogen receptor (ER)-positive breast cancer.
In this model, human estrogen receptor-positive (ER+) breast cancer cells (MCF-7) stably transfected with aromatase (MCF-7Ca) are grown as tumors in ovariectomized female nude mice.
The association of SET index and ESR1 levels with distant relapse risk was evaluated from microarrays of ER-positive breast cancer in two cohorts who received 5 years of tamoxifen alone as adjuvant endocrine therapy (n = 225 and 298, respectively), a cohort who received neoadjuvant chemotherapy followed by tamoxifen and/or aromatase inhibition (n = 122), and two cohorts who received no adjuvant systemic therapy (n = 208 and 133, respectively).
Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.
Although aromatase inhibitors have been used as a first-line therapy for estrogen receptor-positive breast cancer in postmenopausal women, their potential as breast cancer chemopreventive agents has been limited due to toxicities and high costs.
Aromatase is responsible for the rate-determining reaction in estrogen synthesis and is a prime target for treating estrogen-receptor-positive breast cancer.
Lower levels of MLT in aging women may increase the risk of progressing ER-positive breast cancer through a decreased ability to suppress CYP19A1 expression and subsequent local estrogen production in BAFs/CAFs.
Despite the success of the aromatase inhibitors (AIs) in treating estrogen receptor positive breast cancer, 15-20 % of patients receiving adjuvant AIs will relapse within 5-10 years of treatment initiation.