Disease relevance of Women

• Indeed, the proposed use of tamoxifen to prevent breast cancer in high-risk women could result in its extended use during the childbearing years [1].
• BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk [2].
• Jewish Israeli high-risk women who were tested for being carriers of the predominant BRCA1/BRCA2 mutations in Jewish high-risk families were analyzed for the sex of offspring and the rate of spontaneous miscarriages [3].
• Phosphatidylserine-dependent antiprothrombin antibodies are not useful markers for high-risk women with recurrent miscarriages [4].
• With the recent identification of BRCA1, an important predisposition gene for breast and ovarian cancer, genetic testing is becoming available to high-risk women and their families [5].

Psychiatry related information on Women

• Large chemoprevention trials have reported significant breast cancer risk reduction and increased risk of serious adverse events in tamoxifen-treated, high-risk women, which illustrates the need to carefully assess the risk/benefits of this therapy [6].

High impact information on Women

• We developed strategies that entailed no screening for low-risk women, usual care for intermediate-risk women, and universal screening with lower thresholds -- plasma glucose values of 130 mg per deciliter (7.2 mmol per liter) or 128 mg per deciliter (7.1 mmol per liter) -- for high-risk women [7].
• In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women [8].
• RESULTS.--Among 394 subjects from six trials, the RR of PIH among women who took aspirin was 0.35 (95% confidence interval [CI], 0.22 to 0.55) and the number needed to be treated was 4.4, meaning that between four and five high-risk women would need to be treated with aspirin to prevent one case of PIH [9].
• Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women [10].
• Our results failed to support the hypothesis that high-risk women (those with a family history of breast cancer) have relatively lower estriol proportions, and we concluded that whatever family history contributes to breast cancer risk, that risk is not likely to be transmitted by the estrogen profile [11].

Chemical compound and disease context of Women

• RESULTS: Total cholesterol and triglycerides levels were similar in the healthy and the overweight women groups (6.49+/-1.25 vs 6.52+/-1.18 mmol/l; p>0.05 and 1.21+/-0.71 vs 1.41+/-0.98 mmol/l; p>0.05, respectively) [12].

Biological context of Women

• GH response to 67 challenge tests (in control and 'high risk' women) increased between days 4 or 5 and six weeks postpartum (P < 0.05) [13].
• Missense mutations in the BRCT domain of BRCA-1 from high-risk women frequently perturb strongly hydrophobic amino acids conserved among mammals [14].
• The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5% [15].
• The differences in distributions of alleles in AGT M235T (P(a)=0.02) and genotypes in AGT G(-6)A (P(g)=0.017) were found within women groups [16].
• Restricting the analysis to those 3 biomarkers most frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of high-risk women with normal cytology, 19% of high-risk women with epithelial hyperplasia, and 49% of high-risk women with hyperplasia with atypia had abnormalities of 2 or more of these 3 biomarkers (P = .00004) [17].

Anatomical context of Women

• Our findings suggest that defects in the regulation of glucose clearance, glucose production, and plasma FFA concentrations, together with defects in pancreatic beta-cell function, precede the development of type 2 diabetes in these high-risk women [18].
• We report here the baseline findings from a study designed to assess the utility of ductal lavage in this setting.METHODS: Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides [19].
• These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response [20].

Associations of Women with chemical compounds

• High-risk lesions in high-risk women: a high-risk formalin-based biology [21]!
• Effect of long-term therapy with ramipril in high-risk women [22].
• We evaluated mammograms from 28 high-risk women who were taking tamoxifen [23].
• Raloxifene administration is associated with an increase in IGFBP-3 and leptin in premenopausal high risk women [24].
• Vitamin and folic acid supplements were supplied before conception to 44 high risk women before conception [25].

Gene context of Women

• METHOD: Nipple aspiration was performed on 33 high-risk women (defined as having a 5-year Gail model index of more than 1.7, a personal or family history of breast cancer, and/or a BRCA1 or BRCA2 germline mutation) to identify ductal orifices for lavage procedures [26].
• Use of CA-125 and ultrasound in high-risk women [27].
• Overexpression of ER and HER-2/neu occurred in 7 and 20% of high-risk women but in none of the low-risk subjects [17].
• TNF-receptor levels in preeclampsia--results of a longitudinal study in high-risk women [28].
• RESULTS: After adjustment for age and risk-related behaviors, hostility was significantly associated with glucose level and LMD in high-risk women, with LMD in average-risk women, with PAI-1 and LMD in high-risk men, and with fibrinogen level in average-risk men [29].

Analytical, diagnostic and therapeutic context of Women

• Omission of chemotherapy, especially in high-risk women with estrogen receptor-negative tumors who were 50 to 69 years of age, was the most frequent inconsistency with guidelines [30].
• Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women [31].
• Although tamoxifen is approved for the treatment of hormone-dependent breast cancer as well as for the prevention of breast cancer in high-risk women, several studies in animal models have shown that tamoxifen is heptocarcinogenic, and in humans, tamoxifen has been associated with an increased risk of endometrial cancer [32].
• We have undertaken a double-blind placebo-controlled pilot study to assess the feasibility of mounting a large multicentre study of tamoxifen in the prevention of breast cancer in high risk women [33].
• A severely abnormal scan (summed stress score > 8) during adenosine technetium-99m sestamibi myocardial perfusion SPECT had a high sensitivity of 91% and a moderately high specificity of 70% for identifying high-risk women with severe or extensive CAD [34].

References