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While advances in science and technology have increased options for treating breast cancer, current social trends have changed the way people deal with this disease. Women in the United States are no longer simply passive patients, but rather they are survivors, advocates and activists who are speaking up for themselves and speaking out for issues relevant to the treatment and prevention of breast cancer. As the discoveries of basic science have been translated to better clinical treatment, a new sense of hope has emerged. Quality of life now shares the spotlight with quantity of life as breast cancer has shifted from an acute to a chronic condition and as the numbers of long-term survivors increase. While this new population tends to have more optimistic expectations for survival, they are also expressing concerns about issues affecting their lives through and beyond treatment. These issues include, but are not limited to, such concerns as efficient and accurate diagnosis, the complexity of treatment decisions, access to quality cancer care, informed consent, privacy issues, availability of supportive care treatments, and effective communication skills, especially with their physicians. Survivors are also concerned about the impact of their disease on spouses and family, on fertility and sexuality issues, on their employment and (in the USA) insurability, and on their long-term survival. The identification of these increasing issues has given rise to a consumer movement that encourages a shift away from powerless victim to empowered survivor.

Objective: To determine whether oestrogen receptor (ER)a messenger RNA (mRNA) levels or single nucleotide polymorphisms (SNPs) are associated with obesity in Swedish women. Design: ERa mRNA expression levels were measured by real-time qPCR in subcutaneous adipose tissue from non-obese (N ¼ 16, BMI o30) and obese (N ¼ 17, BMI X30) women. In addition, ERa mRNA expression levels were determined in isolated adipocytes. ERa promoter usage was characterized by 5 0 RACE and by real-time qPCR in subcutaneous adipose tissue from the same non-obese and obese women. Two ERa SNPs were scored in 509 non-obese and 489 obese females. Results: ERa mRNA expression levels were lower in obese compared to non-obese women in both subcutaneous adipose tissue and in adipocytes. We show that two ERa promoters are differentially utilized in obese and non-obese individuals. We did not find any significant association between obesity and the ERa SNPs or haplotypes assayed. Conclusion: The reduced ERa mRNA levels observed in adipose tissue from obese compared to non-obese women support a role for oestrogen signaling via ERa, in control of body weight. Mechanistic studies of the role of ERa in adipocytes and how its expression is regulated in relation to fat mass should be performed. The latter studies should focus on the two promoters that are used differently in obese and non-obese individuals.

We have employed fluorescence spectroscopy to study the chemical equilibrium between a 115 amino acid protein fragment containing the DNA-binding domain of the human glucocorticoid receptor (DBDr) and a 24-base-pair DNA oligomer containing the glucocorticoid response element (GRE) from the mouse mammary tumor virus promoter region and compared it with the binding to nonspecific DNA at various ionic conditions. We find that binding to both DNAs is cooperative but that DBDr shows a higher affinity for the GRE than for nonspecific DNA and that this difference is more pronounced at increased salt concentrations. Sequence-specific binding to the GRE sequence at 570 mM monovalent cations can be described by a two-site cooperative model, and this supports the notion that DBDr binding to the GRE is enhanced by dimer formation at the recognition site. The product between the (average) association constant for binding to a GRE half-site and the cooperativity parameter was estimated to be K omega = (1-4) x 10(7) M-1 at this salt concentration and 20 degrees C. The sequence-specific binding is not very sensitive to salt concentration in the interval 270-570 mM monovalent cations. However, at lower salt (70 mM) additional binding takes place, presumably nonspecific (cooperative) association to DNA adjacent to the GRE sequence. DBDr binding to nonspecific DNA can be described by the McGhee-von Hippel model for cooperative binding to a chain polymer and is very sensitive to ionic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)