estradiol levels and aromatase inhibitors in breast cancer

Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI Letrozole (20 μg, p.o.) on cognition, anxiety, thermoregulation, brain estrogen content, and hippocampal pyramidal cell physiology...

BACKGROUND: Invasive lobular breast carcinoma (ILC) is a histological subtype of breast cancer that is characterized by loss of E-cadherin and high expression of estrogen receptor alpha (ERα). In many cases, ILC is effectively treated with adjuvant aromatase inhibitors (AIs); however, acquired AI resistance remains a significant problem. METHODS: To identify underlying mechanisms of acquired anti-estrogen resistance in ILC, we recently developed six long-term estrogen-deprived (LTED) variant cell lines from the human ILC cell lines SUM44PE (SUM44; two lines) and MDA-MB-134VI (MM134; four lines)...

BACKGROUND: Medication adherence refers to whether a patient takes medication according to the frequency prescribed, or continues to take a prescribed medication. Inadequate adherence to medication may cause alterations in risk-benefit ratios, resulting in reduced benefits, increased risks or both, and is significantly associated with adverse clinical outcomes and higher healthcare costs. We aim to examine the effect of a computer generated short message service (SMS) reminder in improving medication adherence, and inhibiting the aromatisation process amongst breast cancer women receiving oral aromatase inhibitor therapy...

BACKGROUND: Among estrogens, estradiol (E2) has the strongest physiological activity as a stimulator in estrogen receptor (ER)-positive breast cancer. The aim of this study is to investigate E2 dynamics during endocrine therapy and to explore the optimal environment in which tamoxifen (TAM) exhibits better efficacy for ER-positive premenopausal early breast cancer patients. METHODS: This is a retrospective study enrolled 194 patients with premenopausal ER-positive early-stage breast cancer who aging ≤45 years at onset and receiving luteinizing hormone-releasing hormone-agonist (LHRH-a) and TAM-therapy...

Background: Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen. Methods: We identified all patients with chemotherapy-induced ovarian function failure...

BACKGROUND: Controlled ovarian hyperstimulation (COH) followed by oocyte retrieval is a leading option for fertility preservation before chemotherapy, yet this procedure causes excessive serum levels of estradiol (E2), which are often detrimental for cancer patients. Aromatase inhibitors are often used in breast cancer patients during COH to prevent elevated levels of E2. OBJECTIVES: To describe our experience with COH for oocyte cryopreservation in non-breast cancer patients using aromatase inhibitors...

Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...

Our previous study showed that the new synthetic methoxy-stilbenes, 3,4,2'-trimethoxy-trans-stilbene (3MS), 3,4,2',4'-tetramethoxy-trans-stilbene (4MS), and 3,4,2',4',6'-pentamethoxy-trans-stilbene (5MS), modulate the constitutive expression of enzymes and receptors involved in estrogen metabolism in breast immortalized epithelial MCF10 cells. In this study, we evaluated the effect of 3MS, 4MS, and 5MS in comparison to resveratrol activity in MCF7 estrogen-dependent and MDA-MB-231 estrogen-independent breast cancer cell lines...

BACKGROUND: Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history. METHODS: Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported at least moderate vaginal symptoms. Participants could be on tamoxifen or aromatase inhibitors (AIs). Women were randomized to 3...

Breast cancer patients who are taking adjuvant Aromatase Inhibitor (AI) therapy typically have extremely low estradiol levels, which are undetectable by routine clinical laboratories. Thus, it becomes difficult to assess the safety of interventions such as low-dose vaginal estrogen, which may increase estradiol levels. In this study, we aimed to assess the utility of enzyme-linked immunosorbent assay (ELISA) to measure low estradiol concentrations in breast cancer survivors on AI therapy treated with either vaginal estrogen or lubricant for atrophic vaginitis as a part of clinical trial...

PURPOSE: Aromatase inhibitors (AI) have been shown to reduce breast cancer-related mortality in women with estrogen positive (ER+) breast cancer. The use of AIs, however, has been associated with higher rates of hypertension, hyperlipidemia, and cardiovascular (CV) events. METHODS: A cross-sectional study of 25 healthy postmenopausal women and 36 women with curative intent breast cancer on an AI was performed to assess endothelial dysfunction, an indicator of risk for CV events...

PROBLEM IDENTIFICATION: Women taking aromatase inhibitors (AIs) as part of the management of hormone receptor-positive breast cancer experience more symptoms of sexual dysfunction, including vaginal atrophy, as opposed to postmenopausal women and women treated with tamoxifen (Nolvadex®). Vaginal testosterone could be an alternative to estrogen, which is contraindicated in this population.
. LITERATURE SEARCH: A systematic review was completed by searching PubMed and Scopus databases...

PURPOSE: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. EXPERIMENTAL DESIGN: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled...

Leptin plays a key role in the control of adipocyte formation, as well as in the associated regulation of energy intake and expenditure. The goal of this study was to determine if leptin-induced aromatase enhances estrogen production and induces tumor cell growth stimulation. To this end, breast cancer cells were incubated with leptin in the absence or presence of inhibitor pretreatment, and changes in aromatase and cyclooxygenase-2 (COX-2) expression were evaluated at the mRNA and protein levels. Transient transfection assays were performed to examine the aromatase and COX-2 gene promoter activities and immunoblot analysis was used to examine protein expression...

Objective  Obesity is associated with an increased risk for breast cancer. Recent studies have shown that aromatase inhibitors may be less effective in women with a high body mass index (BMI). The aim of this study was to establish the relationship between the BMI and plasma estrone and estradiol levels in postmenopausal women with hormone receptor-positive breast cancer using anastrozole. Methods  In this cohort study, the patients were divided into three groups according to BMI (normal weight, overweight and obese) to compare and correlate plasma hormone levels before starting anastrozole hormone therapy and three months after treatment...

Adjuvant treatment with aromatase inhibitors improves outcomes in postmenopausal women with hormone-sensitive early breast cancer; however, they should not be used in premenopausal women. Menopausal status is the most important factor in the choice of the hormonal treatment. There is no direct correlation between amenorrhea and ovarian function, as even the patients with amenorrhea may present with premenopausal plasma estradiol levels. The evaluation of hormonal status becomes more complicated in patients taking tamoxifen, which might lead to further increase of plasma estradiol levels...

BACKGROUND: The third generation aromatase inhibitors (anastrozole, letrozole, exemestane) have become standard endocrine treatment for postmenopausal estrogen receptor - positive breast cancers in all settings (neoadjuvant, adjuvant, metastatic breast cancer), based on superiority to tamoxifen. Aromatase inhibitors interfere with the conversion of androgens into estrogens by blocking the enzyme aromatase resulting in low estradiol levels. Aromatase inhibitors are contraindicated in women with functional ovaries...

PURPOSE: Research on the mechanism of Bushen Jianpi decoction (BJD) for preventing and treating osteoporosis caused by aromatase inhibitors (AI) during treatment for breast cancer resection. METHODS: An ovariectomized mouse model was established using random division into 6 groups: a sham ovariectomized group, a blank control group, a control group, an alendronate group, a BJD group, and a drug combination group. Mice breast cancer cell lines (4T1) were cultured and seeded into the armpits of 6 groups of BALB/c mice...

INTRODUCTION: The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice...

Importance: Aromatase inhibitors (AI) are associated with significant urogenital atrophy, affecting quality of life and drug compliance. Objective: To evaluate safety of intravaginal testosterone cream (IVT) or an estradiol-releasing vaginal ring (7.5 μg/d) in patients with early-stage breast cancer (BC) receiving an AI. Intervention was considered unsafe if more than 25% of patients had persistent elevation in estradiol (E2), defined as E2 greater than 10 pg/mL (to convert to pmol/L, multiply by 3...