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.
To identify common adaptive mechanisms associated with resistance to aromatase inhibitors (AIs), we assessed changes in global gene expression during adaptation to long-term estrogen deprivation (LTED) in a panel of ER+ BC cell lines cultured in 2D on plastic (MCF7, T47D, HCC1428, SUM44 and ZR75.1) or in 3D on collagen (MCF7) to model the stromal compartment.
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).
miR-155 Drives Metabolic Reprogramming of ER+ Breast Cancer Cells Following Long-Term Estrogen Deprivation and Predicts Clinical Response to Aromatase Inhibitors.
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.
The discovery of potent, natural product-based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal-based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor-positive breast cancer and other hormone related indications.
Our study demonstrated genetic polymorphisms of ERalpha, CYP19A1, COMT and p53 genes frequently occur in ER-positive breast cancer in premenopausal Japanese women.
Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER⁺) breast cancer (BC) tumor growth and metastasis.
Anastrozole is an aromatase inhibitor that has been used more frequently over the last decade especially for oestrogen receptor-positive breast cancer.
Estrogen withdrawal by treatment with aromatase inhibitors is the most effective form of endocrine therapy for postmenopausal estrogen receptor-positive (ER+) breast cancer.
The MANTA trial is an open-label, phase 2 randomized clinical trial in which 333 patients with estrogen receptor-positive breast cancer progressing after prior aromatase inhibitor treatment underwent randomization (2:3:3:2) between April 1, 2014, and October 24, 2016, at 88 sites in 9 countries: 67 patients were assigned to receive fulvestrant, 103 fulvestrant plus vistusertib daily, 98 fulvestrant plus vistusertib intermittently, and 65 fulvestrant plus everolimus.
The aromatase inhibitors (AI) exemestane (EXE), letrozole (LET), and anastrozole suppress estrogen biosynthesis, and are effective treatments for estrogen receptor (ER)-positive breast cancer.
Osteoporosis treatment, including vitamin D and bisphosphonates, is associated with a 50% reduction of relapse and death in women treated with aromatase inhibitors for ER+ breast cancer.
Predictive markers in elderly patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors: an array-based pharmacogenetic study.
These findings suggest that patient-specific responses to hormone therapies can be modeled and studied organotypically <i>in vitro</i> and add to evidence advocating obesity as a parameter to consider when identifying treatments for patients with ER-positive breast cancer.-Morgan, M. M., Arendt, L. M., Alarid, E. T., Beebe, D. J., Johnson, B. P. Mammary adipose stromal cells derived from obese women reduce sensitivity to the aromatase inhibitor anastrazole in an organotypic breast model.
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.
This review outlines key issues in the implementation of pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of aromatase inhibitors in postmenopausal women with estrogen receptor positive breast cancer.
The objective of this study is to determine the influence of polymorphisms in the CYP19A1 gene on bone loss among patients taking aromatase inhibitors for ER+ breast cancer.
The USPSTF found convincing evidence that risk-reducing medications (tamoxifen, raloxifene, or aromatase inhibitors) provide at least a moderate benefit in reducing risk for invasive estrogen receptor-positive breast cancer in postmenopausal women at increased risk for breast cancer.
A recent analysis of cell-free DNA from blood samples found that ESR1 mutations are highly prevalent and associated with worse overall survival in women with advanced estrogen receptor-positive breast cancer that progressed on aromatase inhibitor therapy.