Therapy In Postmenopausal Women Research Articles

Effects of raloxifene on cognition in postmenopausal women with schizophrenia: A double-blind, randomized, placebo-controlled trial

Studies of estrogen therapy in postmenopausal women provide evidence of an effect of sex hormones on cognitive function. Estrogen has demonstrated some utility in the prevention of normal, age-related decline in cognitive functions, especially in memory. The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator (SERM), appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems, and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. We assessed the utility of raloxifene as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments. Thirty-three postmenopausal women with schizophrenia (DSM-IV) were randomized to receive either adjuvant raloxifene (16 women) or adjuvant placebo (17 women) for three months. The main outcome measures were: Memory, attention and executive functions. Assessment was conducted at baseline and week 12. The total sample is homogenous with respect to: age, years of schooling, illness duration, baseline symptomatology and pharmacological treatment. The addition of raloxifene (60mg) to regular antipsychotic treatment showed: we found significant differences in some aspects of memory and executive function in patients treated with raloxifene. This improvement does not correlate with clinical improvement. The use of raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia seems to be useful in improving cognitive symptoms.

POSSIBILITY OF THE PRIMARY PREVENTION OF STROKE: DEVELOPING AT THE POPULATION LEVEL

Review is devoted to primary prevention of stroke. Detailed analysed the prevalence of stroke and its contribution to the development of complications and deaths. The basic principles for the prevention of stroke are proved. The article presents the current international recommendations for correction of risk factors (hypertension, smoking, lipid metabolism, diabetes, atrial fibrillation). The significance of asymptomatic carotid artery stenosis as a predictor of stroke presented separately. Modern methods of diagnosis and treatment of carotid artery stenosis are presented. We consider the appropriateness of hormone replacement therapy in postmenopausal women for the prevention of stroke, as well as antiplatelet therapy for primary prevention of stroke, particularly aspirin, which can be used only when there is a high risk of cardiovascular complications. According to the authors, the success of prevention of stroke depends on the implementation of comprehensive and long-term national programs.

Uric Acid and Coronary Collateral Circulation

Coronary collateral (CC) artery development is usually attributed to ischemia, but these anastomotic channels are also present in individuals who do not have coronary artery disease (CAD). The CCs are present in one-fourth of the patients with normal coronary arteries or nonobstructive CAD. Currently, there is no noninvasive method for evaluating CC circulation in humans. The most widely used strategy is visual assessment of collateral arteries as described by Rentrop et al. This method involves balloon occlusion of the contralateral coronary artery, which is rarely performed. In clinical practice, this method is applied without occluding the contralateral vessels. As a result, underestimation of collateralization is inevitable. Other limitations of this visual method include observer variability, influence by the blood pressure, and the force of contrast injection as well as the duration of filming. The most accurate assessment could be obtained by measuring the pressure-derived collateral flow index. Several clinical and angiographic variables including the degree of coronary stenosis, proximal lesion location, longer duration of symptoms, and occlusion as well as resting bradycardia have been reported as variables that correlated with the degree of collateralization. Also, in patients without CAD, the baseline heart rate has been described as the main predictor of collateralization. The most important trigger for collateral growth is tangential (radial) fluid shear stress at the endothelial level with the recruitment of bone marrow-derived mononuclear cells. It is a remodeling process of preexisting small collateral arterioles rather than the growth of new capillary vessels, which is induced by ischemia. Collateral growth is induced by fluid shear stress in preformed collateral vessels caused by a pressure gradient between the area proximal to a coronary stenosis and the low-pressure poststenotic area. The CCs play a role in preserving myocardial function, limiting infarct size, and increasing survival. However, a meta-analysis showed that a well-developed collateral circulation was a risk factor for restenosis after coronary revascularization. In humans, uric acid (UA) is generated from purine catabolism with the conversion of hypoxanthine to xanthine and of xanthine to UA by the enzyme xanthine oxidoreductase. It is further oxidized to allantoin in most species except humans and some higher primates who lack uricase. Therefore, serum UA (SUA) levels in humans are appreciably higher than in other mammals. Because of this difference in urate metabolism, the results of animal studies can be difficult to interpret. Also, different methods of measuring collateral flow may be applied in animal studies. Many patients with CAD use at least 1 drug that can influence SUA levels (eg, aspirin, statins, fibrates, and some antihypertensive agents). The SUA levels are higher in men than in women at all ages due to gender steroids. Sumino et al showed that hormone replacement therapy in postmenopausal women was associated with a significant reduction in SUA level. Also, dietary, environmental, and genetic factors are important determinants of SUA levels. It is important to note that UA is a potent antioxidant, but it can also be a prooxidant if the level is >6 mg/dL in women and 6.5 to 7.0 mg/dL in men. Therefore, elevated SUA level might be an indicator of increased burden of oxidant attack. Besides its dual oxidant effect, if UA is a harmful product, why do our kidneys recover 90% of filtered UA instead of eliminating it? Despite the antioxidant properties of UA, several studies have indicated that high SUA levels are associated with several disorders, including CAD, peripheral arterial disease, heart failure, metabolic syndrome, hypertension, and stroke. These associations have been mainly attributed to upregulation of renin release and the subsequent cascade-related reduction in endothelial function. However, instead of proven causal associations, possible explanations with small study groups could be reverse causality. For example, preclinical atherosclerosis could lead to higher levels of SUA. In contrast, experts from the Framingham Heart Study group have reported no association between the SUA and the cardiovascular disease. In a recently published study, Palmer et al investigated the association of plasma UA with CAD and hypertension using Mendelian randomization. They found no evidence of a causal effect of UA or hyperuricemia on the risk of CAD and hypertension. Recently, some studies have demonstrated an association between SUA and CC development in patients with CAD and

Strengthening the bones in primary biliary cirrhosis

Strengthening the bones in primary biliary cirrhosis

Expansion of CD11b(+)Ly6G (+)Ly6C (int) cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions.

The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored whether exposure to MPA during mammary tumor growth affects myeloid-derived suppressor cells (MDSCs; CD11b(+)Gr-1(+), mostly CD11b(+)Ly6G(+)Ly6C(int) and CD11b(+)Ly6G(-)Ly6C(high) cells) and natural killer (NK) cells, potentially restraining tumor immunosurveillance. We used the highly metastatic 4T1 breast tumor (which does not express the classical progesterone receptor and expands MDSCs) to challenge BALB/c mice in the absence or in the presence of MPA. We observed that MPA promoted the accumulation of NK cells in spleens of tumor-bearing mice, but with reduced degranulation ability and in vivo cytotoxic activity. Simultaneously, MPA induced a preferential expansion of CD11b(+)Ly6G(+)Ly6C(int) cells in spleen and bone marrow of 4T1 tumor-bearing mice. In vitro, MPA promoted nuclear mobilization of the glucocorticoid receptor (GR) in 4T1 cells and endowed these cells with the ability to promote a preferential differentiation of bone marrow cells into CD11b(+)Ly6G(+)Ly6C(int) cells that displayed suppressive activity on NK cell degranulation. Sorted CD11b(+)Gr-1(+) cells from MPA-treated tumor-bearing mice exhibited higher suppressive activity on NK cell degranulation than CD11b(+)Gr-1(+) cells from vehicle-treated tumor-bearing mice. Thus, MPA, acting through the GR, endows tumor cells with an enhanced capacity to expand CD11b(+)Ly6G(+)Ly6C(int) cells that subsequently display a stronger suppression of NK cell-mediated anti-tumor immunity. Our results describe an alternative mechanism by which MPA may affect immunosurveillance and have potential implication in breast cancer incidence.

Evaluating the 21-gene assay Recurrence Score® as a predictor of clinical response to 24 weeks of neoadjuvant exemestane in estrogen receptor-positive breast cancer

The aim of this study was to investigate the association between the results of the Recurrence Score (RS) assay and the clinical response to neoadjuvant endocrine therapy in postmenopausal women with breast cancer. Core biopsy samples at baseline and post-treatment surgical samples were obtained from 80 and 77 of 116 patients, respectively, enrolled in the multicenter prospective study of neoadjuvant exemestane therapy (JFMC34-0601). The 21-gene assay was performed after appropriate manual microdissection. The estrogen receptor (ER), progesterone receptor, HER2 and Ki-67 were assayed by immunohistochemistry at a central laboratory. Clinical response was assessed based on the RECIST (Response Evaluation Criteria In Solid Tumors) guideline. Sixty-four core biopsy samples and 52 resection samples met the RS quality requirements. The clinical response rate in those patients with a low RS result (low RS group; 19/32, 59.4 %) was significantly higher than that in those patients with a high RS result (high RS group; 3/15, 20.0 %) (P = 0.015) and similar to that in patients with an intermediate RS result (intermediate RS group; 10/17, 58.8 %). The rates of breast-conserving surgery (BCS) were 90.6 % (29/32) in the low RS group, 76.5 % (13/17) in the intermediate RS group and 46.7 % (7/15) in the high RS group. The odds ratio for BCS adjusted for continuous baseline Ki-67 was 0.114 [95 % confidence interval (CI) 0.014-0.721; P = 0.028] between the high and low RS groups. RS values in pre-treatment samples were highly correlated with those in post-treatment samples (Spearman correlation coefficient 0.745, 95 % CI 0.592-0.846). Our results demonstrate the predictive value of the RS for clinical response to neoadjuvant exemestane therapy in postmenopausal women with ER-positive breast cancer.

Circulation Editors’ Picks

<i>Circulation</i> Editors’ Picks

Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer

BackgroundThe progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies. Patients and methodsThis randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer. ResultsPatients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥6 months. Overall, 61 of 68 patients (90%) had ≥1 adverse event (AE), the most frequent (≥10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs. ConclusionLonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.

The Risk of Ischemic Heart Disease With Adjuvant Endocrine Therapy in Postmenopausal Women With Early Stage Breast Cancer

The Risk of Ischemic Heart Disease With Adjuvant Endocrine Therapy in Postmenopausal Women With Early Stage Breast Cancer

Immunohistochemical BAG1 expression improves the estimation of residual risk by IHC4 in postmenopausal patients treated with anastrazole or tamoxifen: a TransATAC study

BAG1 is a multifunctional anti-apoptotic protein located on chromosome 9q12, which binds to Bcl-2. BAG1 is present as a separate module in the GHI-RS 21-gene panel. It may provide additional prognostic information as an immunohistochemical marker when added to IHC4. Analysis of BAG1 was performed on archival tumour blocks from patients from the anastrozole and tamoxifen arms of the ATAC trial of 5years endocrine therapy in postmenopausal women with oestrogen receptor (ER)-positive primary breast cancer. Staining was scored separately as nuclear or cytoplasmic. Statistical analyses were performed on data from median 10-year follow-up with distant recurrence as primary endpoint. Data on both nuclear and cytoplasmic BAG1 as well as the IHC4 markers (ER, PgR, HER2 and Ki67) were available on 963 ER-positive cases of which 860 were HER2-negative. Cytoplasmic and nuclear BAG1 were highly correlated (Spearman r=0.79, p<00001). Women with higher BAG1 expression developed 30% fewer distant recurrences compared to those with low expression. Nuclear BAG1 contributed significantly to the clinical and IHC4 models with added information being greater in node-positive cases. Similar results were seen if all recurrences were the endpoints. BAG1 expression provides significant prognostic information when added to the classical clinicopathological parameters and IHC4, particularly in node-positive patients.

Quantitative Determination of Anastrozole by Liquid Chromatography–Tandem Mass Spectrometry

Anastrozole is a potent and selective non-steroidal aromatase inhibitor and is used for therapy of postmenopausal women with hormone-receptor-positive breast cancer. This paper provides a detailed description of the determination of anastrozole in human plasma by liquid chromatography–mass spectrometry (LC–MS–MS). Plasma-sample pretreatment involved solid-phase extraction using Accubond SPE ODS-C18 cartridges. Chromatographic separation was carried out on a Zorbax Bonus-RP column with a mobile phase consisting of aqueous formic acid (0.2%) (eluent A) and MeOH (eluent B) with a ratio A:B = 30:70 (v/v) that was supplied at flow rate 0.2 mL/min. Detection was performed on an Agilent 6410-2K triple quadrupole tandem mass spectrometer by multiple reaction monitoring in the preset mass range 294.2 → 225.1 using atmospheric-pressure chemical ionization in positive-ion mode. A calibration curve for anastrozole was linear (R2 ≥ 0.97) over the concentration range 0.5 – 20.0 ng/mL with a lower detection limit of 0.5 ng/mL. The described procedures can be applied successfully to both therapeutic monitoring of anastrozole and drug bioequivalence studies.

Potential Role of Labisia pumila in the Prevention and Treatment of Chronic Diseases

&lt;p&gt;&lt;em&gt;Labisia pumila&lt;/em&gt; (Myrsinaceae), also called Kacip Fatimah, is a herbal medicine that has been widely used in South East Asian communities mainly for women’s health. The extensive use of this plant has led to many speculations and studies on its phytoestrogenic properties. This review highlights the studies that involved&lt;em&gt; Labisia pumila,&lt;/em&gt; which include phytochemical profiling and its safety. In addition, we also look into its use as an alternative to hormonal therapy in postmenopausal women, and its role in cardiovascular protection and osteoporosis. Further studies are needed to highlight the potential benefits of this plant in promoting advantageous health properties. &lt;em&gt;&lt;/em&gt;&lt;/p&gt;

The Patient's Anastrozole Compliance to Therapy (PACT) Program: a randomized, in-practice study on the impact of a standardized information program on persistence and compliance to adjuvant endocrine therapy in postmenopausal women with early breast cancer

BackgroundCompliance and persistence are often overlooked in adjuvant breast cancer treatment. Patients and methodsPACT was a prospective, multicenter, randomized, open, parallel-group study assessing whether educational materials (EMs) enhanced compliance with aromatase inhibitor (AI) therapy in postmenopausal women with early, hormone-receptor-positive (HR+) breast cancer. The primary end points were compliance (proportion taking ≥80% anastrozole) at 12 months and persistence (proportion reporting anastrozole intake during the study period). ResultsFour thousand eight hundred and forty-four patients were randomly assigned 1:1 to receive standard therapy or standard therapy with EMs. There was no difference between arms in compliance (N = 2740; 88.5%/88.8%, respectively, P = 0.81) or persistence rates (N = 2740; 40.5%/43.0%, respectively, P = 0.18). Modified end point analyses found no differences in compliance between arms based on the classification of: (i) patients with missing documentation or follow-up visit <9 months as non-compliant (N = 4397, P = 0.15); (ii) patients with early (≤292 days) 12-month follow-up documentation excluded (N = 4091, P = 0.19); (iii) patients reaching ≥80% compliance during individual follow-up as compliant (N = 4397, P = 0.26). Modified persistence analyses found no difference between arms (N = 4397, P = 0.37). ConclusionsAddition of EMs to standard therapy did not significantly affect compliance and persistence with adjuvant anastrozole. ClinicalTrials IDNCT00555867.

Evaluation of DNA Damage in the Lymphocytes of Young, Elderly and Alzheimer’s Disease Patients Treated with β-Estradiol in the Comet Assay

Summary Background: The antioxidant activity of estrogen has a be ne - ficial impact in Alzheimer’s disease. A variety of clinical stu - dies have demonstrated that estrogen replacement therapy in postmenopausal women results in a lower frequency of AD, delaying the onset of the neurodegenerative cascade. On the other hand, it has been demonstrated that estrogens may exhibit genotoxic effects, especially at elevated tissue concentrations. Therefore, the aim of this study was to determine whether b-estradiol induces DNA damage in the peripheral blood lymphocytes of healthy young females and males, healthy elderly females and males and females and males with Alzheimer’s disease. Methods: All experiments were performed using the alkaline version of the Comet assay (single cell gel electrophoresis), on six donors per each experimental group and controls. Results: In the Comet assay, a significant increase of DNA migration was observed in the lymphocytes of all treated groups (young and elderly females, young and elderly males, AD females and AD males) at all b-estradiol concentrations (50 mmol/L, 100 mmol/L and 250 mmol/L) used in this investigation. In all the experiments cell viability was over 80%. Conclusions: Lymphocytes are sensitive to the test concentrations of b-estradiol in the Comet assay regardless of gender, age and health condition of the examined subjects. Therefore, the role of b-estradiol in cellular DNA damage has been confirmed.

THU0385 Utility of the Treatment Thresholds in Frax Proposed by the NOF and the NOGG in Patients with Breast Cancer in Adjuvant Treatment with Aromatase Inhibitors

BackgroundAromatase Inhibitors (AI) are an important component in adjuvant therapy in postmenopausal women with positive estrogenic receptors in breast cancer. They inhibit the enzyme Cytochrome P450 CYP19, which causes a...

53O_PR - Predicting Risk for Late Metastasis: the PAM50 Risk of Recurrence (ROR) Score After 5 Years of Endocrine Therapy in Postmenopausal Women with Hr+ Early Breast Cancer: a Study On 1,478 Patients from the Abcsg-8 Trial

53O_PR - Predicting Risk for Late Metastasis: the PAM50 Risk of Recurrence (ROR) Score After 5 Years of Endocrine Therapy in Postmenopausal Women with Hr+ Early Breast Cancer: a Study On 1,478 Patients from the Abcsg-8 Trial

Blood pressure regulation in women – differences emerge when challenged by orthostasis

Blood pressure regulation in women – differences emerge when challenged by orthostasis

Patient's Anastrozole Compliance to Therapy (PACT) Program: Baseline Data and Patient Characteristics from a Population-Based, Randomized Study Evaluating Compliance to Aromatase Inhibitor Therapy in Postmenopausal Women with Hormone-Sensitive Early Breast Cancer

Background: The Patient's Anastrozole Compliance to Therapy (PACT) program is a large randomized study designed to assess whether the provision of educational materials (EM) could improve compliance with aromatase inhibitor therapy in postmenopausal women with early, hormone receptor-positive breast cancer. Patients and Methods: The PACT study presented a large, homogeneous dataset. The baseline analysis included patient demographics and initial treatments and patient perceptions about treatment and quality of life. Results: Overall, 4,923 patients were enrolled at 109 German breast cancer centers/clinics in cooperation with 1,361 office-based gynecologists/oncologists. 4,844 women were randomized 1:1 to standard therapy (n = 2,402) or standard therapy plus EM (n = 2,442). Prior breast-conserving surgery and mastectomy had been received by 76% and 24% of the patients, respectively. Radiotherapy was scheduled for 85% of the patients, adjuvant chemotherapy for 38%. Reflecting the postmenopausal, hormone-sensitive nature of this population, only 285 patients (7%) had received neoadjuvant chemotherapy. Conclusions: A comparison with epidemiological data from the West German Breast Center suggests that the patients in the PACT study are representative of a general postmenopausal early breast cancer population and that the findings may be applicable to ‘real-world' Germany and beyond. Compliance data from PACT are eagerly anticipated.

Applications of CYP450 Testing in the Clinical Setting

Interindividual variability in drug response is a major clinical problem. Polymedication and genetic polymorphisms modulating drug-metabolising enzyme activities (cytochromes P450, CYP) are identified sources of variability in drug responses. We present here the relevant data on the clinical impact of the major CYP polymorphisms (CYP2D6, CYP2C19 and CYP2C9) on drug therapy where genotyping and phenotyping may be considered, and the guidelines developed when available. CYP2D6 is responsible for the oxidative metabolism of up to 25 % of commonly prescribed drugs such as antidepressants, antipsychotics, opioids, antiarrythmics and tamoxifen. The ultrarapid metaboliser (UM) phenotype is recognised as a cause of therapeutic inefficacy of antidepressant, whereas an increased risk of toxicity has been reported in poor metabolisers (PMs) with several psychotropics (desipramine, venlafaxine, amitriptyline, haloperidol). CYP2D6 polymorphism influences the analgesic response to prodrug opioids (codeine, tramadol and oxycodone). In PMs for CYP2D6, reduced analgesic effects have been observed, whereas in UMs cases of life-threatening toxicity have been reported with tramadol and codeine. CYP2D6 PM phenotype has been associated with an increased risk of toxicity of metoprolol, timolol, carvedilol and propafenone. Although conflicting results have been reported regarding the association between CYP2D6 genotype and tamoxifen effects, CYP2D6 genotyping may be useful in selecting adjuvant hormonal therapy in postmenopausal women. CYP2C19 is responsible for metabolising clopidogrel, proton pump inhibitors (PPIs) and some antidepressants. Carriers of CYP2C19 variant alleles exhibit a reduced capacity to produce the active metabolite of clopidogrel, and are at increased risk of adverse cardiovascular events. For PPIs, it has been shown that the mean intragastric pH values and the Helicobacter pylori eradication rates were higher in carriers of CYP2C19 variant alleles. CYP2C19 is involved in the metabolism of several antidepressants. As a result of an increased risk of adverse effects in CYP2C19 PMs, dose reductions are recommended for some agents (imipramine, sertraline). CYP2C9 is responsible for metabolising vitamin K antagonists (VKAs), non-steroidal anti-inflammatory drugs (NSAIDs), sulfonylureas, angiotensin II receptor antagonists and phenytoin. For VKAs, CYP2C9 polymorphism has been associated with lower doses, longer time to reach treatment stability and higher frequencies of supratherapeutic international normalised ratios (INRs). Prescribing algorithms are available in order to adapt dosing to genotype. Although the existing data are controversial, some studies have suggested an increased risk of NSAID-associated gastrointestinal bleeding in carriers of CYP2C9 variant alleles. A relationship between CYP2C9 polymorphisms and the pharmacokinetics of sulfonylureas and angiotensin II receptor antagonists has also been observed. The clinical impact in terms of hypoglycaemia and blood pressure was, however, modest. Finally, homozygous and heterozygous carriers of CYP2C9 variant alleles require lower doses of phenytoin to reach therapeutic plasma concentrations, and are at increased risk of toxicity. New diagnostic techniques made safer and easier should allow quicker diagnosis of metabolic variations. Genotyping and phenotyping may therefore be considered where dosing guidelines according to CYP genotype have been published, and help identify the right molecule for the right patient.

Abstract 199: Short-term treatment with pregnancy levels of estradiol prevents breast cancer by delaying promotion and progression.

Abstract A full term pregnancy early in life reduces the risk of breast cancer in women. A similar phenomenon is also observed in rats and mice. Recent findings indicate that estradiol alone replacement therapy in postmenopausal women also reduces the risk of breast cancer. We have earlier demonstrated that short-term treatment with pregnancy levels of estradiol (STET) is very effective in preventing mammary carcinogenesis. In the current study our objective was to determine whether STET conferred protection against mammary carcinogenesis by blocking initiation or promotion. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age and divided into 2 groups. One group (n=30) did not receive any further treatment and served as controls and the second group (n=30) of rats was treated with 1 microgram of estradiol per day for 3 weeks using a subcutaneous implant of Alzet osmotic mini pump. A subset (n=5) were terminated 3 and 6 months post carcinogen treatment. The other animals were terminated 9 months post carcinogen treatment. Mammary gland wholemounts were prepared at each termination timepoint and examined for the presence of latent microscopic mammary cancers (LMMC). In another experiment we surgically isolated LMMC and transplanted them back into a host from the same group (control to control or STET to STET) or to a host from the other group (control to STET or STET to control). Short-term treatment with pregnancy levels of estradiol drastically reduced the incidence of overt mammary cancers. Although a significant reduction of overt cancers was observed in the pregnancy levels of estradiol treated groups, there was no difference in the incidence of LMMC between the estradiol treated and the controls. LMMC were isolated from the mammary glands. Breast cancer and estrogen receptor signaling specific microarrays were performed to find differences in gene expression in LMMC between the controls and STET groups. We were able to identify clear differences in gene expression in LMMC between the two groups. Genes involved in angiogenesis (Thbs1, Vegfa), apoptosis (Bad, Bcl2) and cell cycle (Ccnd1, Cdk2) were differentially expressed. Further several transcription factors (Esr1, Esr2, Gata3, Rb1) were also differentially expressed in LMMC between the controls and STET groups. The transplantation experiment indicated that the progression of LMMC was dependent on the systemic environment it is exposed to. The LMMC derived from control were not able to progress further to make overt cancers when transplanted STET hosts, while the LMMC derived from STET were able to progress to overt cancers when transplanted to control hosts. These findings demonstrate that STET confers protection against mammary cancer development by blocking promotion and progression of transformed cells. Understanding this phenomenon shall assist in the design of novel prevention and therapeutic strategies against breast cancer. Citation Format: Arunkumar Arumugam, Maricarmen Stout, Cathy Tsin, Amar Bhat, Taylor Yong, Sushmita Nandy, Christina Gutierrez, Rebecca Lopez, Thiyagarajan Boopalan, Jacqueline Parada, Rajkumar Lakshmanaswamy. Short-term treatment with pregnancy levels of estradiol prevents breast cancer by delaying promotion and progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 199. doi:10.1158/1538-7445.AM2013-199