Predictors of onset of depression and anxiety in the year after diagnosis of breast cancer

Background Depression and anxiety are common after diagnosis of breast cancer. We examined to what extent these are recurrences of previous disorder and, controlling for this, whether shame, self-blame and low social support after diagnosis predicted onset of depression and anxiety subsequently. Method Women with primary breast cancer who had been treated surgically self-reported shame, self-blame, social support and emotional distress post-operatively. Psychiatric interview 12 months later identified those with adult lifetime episodes of major depression (MD) or generalized anxiety disorder (GAD) before diagnosis and onset over the subsequent year. Statistical analysis examined predictors of each disorder in that year. Results Of the patients, two-thirds with episodes of MD and 40% with episodes of GAD during the year after diagnosis were experiencing recurrence of previous disorder. Although low social support, self-blame and shame were each associated with both MD and GAD after diagnosis, they did not mediate the relationship of disorder after diagnosis with previous disorder. Low social support, but not shame or self-blame, predicted recurrence after controlling for previous disorder. Conclusions Anxiety and depression during the first year after diagnosis of breast cancer are often the recurrence of previous disorder. In predicting disorder following diagnosis, self-blame and shame are merely markers of previous disorder. Low social support is an independent predictor and therefore may have a causal role.

The perception of support received from breast care nurses by depressed patients following a diagnosis of breast cancer

INTRODUCTION Due to their specialist training, breast care nurses (BCNs) should be able to detect emotional distress and offer support to breast cancer patients. However, patients who are most distressed after diagnosis generally experience least support from care staff. To test whether BCNs overcome this potential barrier, we compared the support experienced by depressed and non-depressed patients from their BCNs and the other main professionals involved in their care: surgeons and ward nurses. PATIENTS AND METHODS Women with primary breast cancer (n = 355) 2–4 days after mastectomy or wide local excision, self-reported perceived professional support and current depression. Analysis of variance compared support ratings of depressed and non-depressed patients across staff types. RESULTS There was evidence of depression in 31 (9%) patients. Depressed patients recorded less surgeon and ward nurse support than those who were not depressed but the support received by patients from the BCN was high, whether or not patients were depressed. CONCLUSIONS BCNs were able to provide as much support to depressed patients as to non-depressed patients, whereas depressed patients felt less supported by surgeons and ward nurses than did non-depressed patients. Future research should examine the basis of BCNs' ability to overcome barriers to support in depressed patients. Our findings confirm the importance of maintaining the special role of the BCN.

Oestrogenic activity of benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) in MCF7 human breast cancer cells in vitro

Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to bodycare cosmetics used around the human breast. We report here that all three compounds possess oestrogenic activity in assays using the oestrogen-responsive MCF7 human breast cancer cell line. At 3 000 000-fold molar excess, they were able to partially displace [H-3]oestradiol from recombinant human oestrogen receptors ER alpha and ER beta, and from cytosolic ER of MCF7 cells. At concentrations in the range of 5 x 10(-5) to 5 x 10(-4) M, they were able to increase the expression of a stably integrated oestrogen-responsive reporter gene (ERE-CAT) and of the endogenous oestrogen-responsive pS2 gene in MCF7 cells, albeit to a lesser extent than with 10(-8) M 17 beta-oestradiol. They increased the proliferation of oestrogen-dependent MCF7 cells over 7 days, which could be inhibited by the antioestrogen fulvestrant, suggesting an ER-mediated mechanism. Although the extent of stimulation of proliferation over 7 days was lower with these compounds than with 10(-8) M 17 beta-oestradiol, given a longer time period of 35 days the extent of proliferation with 10(-4) M benzyl salicylate, benzyl benzoate or butylphenylmethylpropional increased to the same magnitude as observed with 10(-8) M 17 beta-oestradiol over 14 days. This demonstrates that benzyl salicylate, benzyl benzoate and butylphenylmethylpropional are further chemical components of cosmetic products which give oestrogenic responses in a human breast cancer cell line in culture. Further research is now needed to investigate whether oestrogenic responses are detectable using in vivo models and the extent to which these compounds might be absorbed through human skin and might enter human breast tissues. Copyright (C) 2009 John Wiley & Sons, Ltd.

Use of global gene expression patterns in mechanistic studies of oestrogen action in MCF7 human breast cancer cells

Over the years, the MCF7 human breast cancer cell line has provided a model system for the study of cellular and molecular mechanisms in oestrogen regulation of cell proliferation and in progression to oestrogen and antioestrogen independent growth. Global gene expression profiling has shown that oestrogen action in MCF7 cells involves the coordinated regulation of hundreds of genes across a wide range of functional groupings and that more genes are down regulated than upregulated. Adaptation to long-term oestrogen deprivation, which results in loss of oestrogen-responsive growth, involves alterations to gene patterns not only at early time points (0-4 weeks) but continuing through to later times (20-55 weeks), and even involves alterations to patterns of oestrogen-regulated gene expression. Only 48% of the genes which were regulated >= 2-fold by oestradiol in oestrogen-responsive cells retained this responsiveness after long-term oestrogen deprivation but other genes developed de novo oestrogen regulation. Long-term exposure to fulvestrant, which resulted in loss of growth inhibition by the antioestrogen, resulted in some very large fold changes in gene expression up to 10,000-fold. Comparison of gene profiles produced by environmental chemicals with oestrogenic properties showed that each ligand gave its own unique expression profile which suggests that environmental oestrogens entering the human breast may give rise to a more complex web of interference in cell function than simply mimicking oestrogen action at inappropriate times. (C) 2009 Elsevier Ltd. All rights reserved.

Oestrogenic and androgenic activity of triclosan in breast cancer cells

As a consequence of its widespread use as an antimicrobial agent in consumer goods, triclosan has become distributed ubiquitously across the ecosystem, and recent reports that it can cause endocrine disruption in aquatic species has increased concern. It is reported here that triclosan possesses intrinsic oestrogenic and androgenic activity in a range of assays in vitro which could provide some explanation for the endocrine disrupting properties described in aquatic populations. In terms of oestrogenic activity, triclosan displaced [H-3]oestradiol from oestrogen receptors (ER) of MCF7 human breast cancer cells and from recombinant human ER alpha/ER beta. Triclosan at 10(-5) M completely inhibited the induction of the oestrogen-responsive ERE-CAT reporter gene in MCF7 cells by 10(-10) M 17 beta-oestradiol and the stimulation of growth of MCF7 human breast cancer cells by 10(-10) M 17 beta-oestradiol. On its own, 1 mu M triclosan increased the growth of MCF7 cells over 21 days. Triclosan also had androgenic activity. It displaced [H-3]testosterone from binding to the ligand binding domain of the rat androgen receptor (AR). Triclosan was able to inhibit the induction of the androgen-responsive LTR-CAT reporter gene in S115 mouse mammary tumour cells by 10(-9) M testosterone and in T47D human breast cancer cells by 10(-8) M testosterone at concentrations of 10(-7) M and 10(-6) M, respectively. Triclosan at 2 x 10(-5) M antagonized the stimulation of the growth of S115+A mouse mammary tumour cells by 10(-9) M testosterone. The finding that triclosan has oestrogenic and androgenic activity warrants further investigation in relation to both endocrine disruption of aquatic wildlife and any possible impact on human health. Copyright (C) 2007 John Wiley & Sons, Ltd.

Effect of sulphation on the oestrogen agonist activity of the phytoestrogens genistein and daidzein in MCF-7 human breast cancer cells

The phytoestrogens genistein, daidzein and the daidzein metabolite equol have been shown previously to possess oestrogen agonist activity. However, following consumption of soya diets, they are found in the body not only as aglycones but also as metabolites conjugated at their 4'- and 7-hydroxyl groups with sulphate. This paper describes the effects of monosulphation on the oestrogen agonist properties of these three phytoestrogens in MCF-7 human breast cancer cells in terms of their relative ability to compete with [H-3]oestradiol for binding to oestrogen receptor (ER), to induce a stably transfected oestrogen-responsive reporter gene (ERE-CAT) and to stimulate cell growth. In no case did sulphation abolish activity. The 4'-sulphadon of genistein reduced oestrogen agonist activity to a small extent in whole-cell assays but increased the relative binding affinity to ER. The 7-sulphation of genistein, and also of equol, reduced oestrogen agonist activity substantially in all assays. By contrast, the position of monosulphation of daidzein acted in an opposing manner on oestrogen agonist activity. Sulphation at the 4'-position of daidzein resulted in a modest reduction in oestrogen agonist activity but sulphation of daidzein at the 7-position resulted in an increase in oestrogen agonist activity. Molecular modelling and docking studies suggested that the inverse effects of sulphation could be explained by the binding of daidzein into the ligand-binding domain of the ER in the opposite orientation compared with genistein and equol. This is the first report of sulphation enhancing activity of an isoflavone and inverse effects of sulphation between individual phytoestrogens.

Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17 beta-oestradiol in MCF7 human breast cancer cells

Since the alkyl esters of p-hydroxybenzoic acid (parabens) can be measured intact in the human breast and possess oestrogenic properties, it has been suggested that they could contribute to an aberrant burden of oestrogen signalling in the human breast and so play a role in the rising incidence of breast cancer. However, although parabens have been shown to regulate a few single genes (reporter genes, pS2, progesterone receptor) in a manner similar to that of 17 beta-oestradiol, the question remains as to the full extent of the similarity in the overall gene profile induced in response to parabens compared with 17 beta-oestradiol. The GE-Amersham CodeLink 20 K human expression microarray system was used to profile the expression of 19881 genes in MCF7 human breast cancer cells following a 7-day exposure to 5 x 10(-4) m methylparaben, 10(-5) m n-butylparaben and 10(-8) m 17 beta-oestradiol. At these concentrations, the parabens gave growth responses in MCF7 cells of similar magnitude to 17 beta-oestradiol. The study identified genes which are upregulated or downregulated to a similar extent by methylparaben, n-butylparaben and 17 beta-oestradiol. However, the majority of genes were not regulated in the same way by all three treatments. Some genes responded differently to parabens from 17 beta-oestradiol, and furthermore, differences in expression of some genes could be detected even between the two individual parabens. Therefore, although parabens possess oestrogenic properties, their mimicry in terms of global gene expression patterns is not perfect and differences in gene expression profiles could result in consequences to the cells that are not identical to those following exposure to 17 beta-oestradiol. Copyright (c) 2006 John Wiley & Sons, Ltd.

Environmental oestrogens, cosmetics and breast cancer

The established role of oestrogen in the development and progression of breast cancer raises questions concerning a potential contribution from the many chemicals in the environment which can enter the human breast and which have oestrogenic activity. A range of organochlorine pesticides and polychlorinated bipheryls possess oestrogen-mimicking properties and have been measured in human breast adipose tissue and in human milk. These enter the breast from varied environmental contamination of food, water and air, and due to their lipophilic properties can accumulate in breast fat. However, it is emerging that the breast is also exposed to a range of oestrogenic chemicals applied as cosmetics to the underarm and breast area. These cosmetics are left on the skin in the appropriate area, allowing a more direct dermal absorption route for breast exposure to oestrogenic chemicals and allowing absorbed chemicals to escape systemic metabolism. This review considers evidence in support of a functional role for the combined interactions of cosmetic chemicals with environmental oestrogens, pharmacological oestrogens, phyto-oestrogens and physiological oestrogens in the rising incidence of breast cancer.

Changes in oestrogen receptor-alpha and -beta during progression to acquired resistance to tamoxifen and fulvestrant (Faslodex, ICI 182,780) in MCF7 human breast cancer cells

Cell culture models of antioestrogen resistance often involve applying selective pressures of oestrogen deprivation simultaneously with addition of tamoxifen or fulvestrant (Faslodex, ICI 182,780) which makes it difficult to distinguish events in development of antioestrogen resistance from those in loss of response to oestrogen or other components. We describe here time courses of loss of antioestrogen response using either oestrogen-maintained or oestrogen-deprived MCF7 cells in which the only alteration to the culture medium was addition of 10(-6) M tamoxifen or 10(-7) M fulvestrant. In both oestrogen-maintained and oestrogen-deprived models, loss of growth response to tamoxifen was not associated with loss of response to fulvestrant. However, loss of growth response to fulvestrant was associated in both models with concomitant loss of growth response to tamoxifen. Measurement of oestrogen receptor alpha (ER alpha) and oestrogen receptor beta (ER beta) mRNA by real-time RT-PCR together with ER alpha and ER beta protein by Western immunoblotting revealed substantial changes to ER alpha levels but very little alteration to ER beta levels following development of antioestrogen resistance. In oestrogen-maintained cells, tamoxifen resistance was associated with raised levels of ERa mRNA/protein. However by contrast, in oestrogen-deprived MCF7 cells, where oestrogen deprivation alone had already resulted in increased levels of ERa mRNA/protein, long-term tamoxifen exposure now reduced ER alpha levels. Whilst long-term exposure to fulvestrant reduced ERa. mRNA/protein levels in the oestrogen-maintained cells to a level barely detectable by Western immunoblotting and non-functional in inducing gene expression (ERE-LUC reporter or pS2), in oestrogen-deprived cells the reduction was much less substantial and these cells retained an oestrogen-induction of both the ERE-LUC reporter gene and the endogenous pS2 gene which could still be inhibited by antioestrogen. This demonstrates that whilst ER alpha can be abrogated by fulvestrant and increased by tamoxifen in some circumstances, this does not always hold true and mechanisms other than alteration to ER must be involved in the development of antioestrogen resistant growth. (c) 2006 Elsevier Ltd. All rights reserved.

Aluminium, antiperspirants and breast cancer

Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metal I oestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer. (c) 2005 Elsevier Inc. All rights reserved.

Recorded quadrant incidence of female breast cancer in Great Britain suggests a disproportionate increase in the upper outer quadrant of the breast

Background: The upper outer quadrant (UOQ) of the breast is the most frequent site for incidence of breast cancel; but the reported disproportionate incidence in this quadrant appears to rise with year of publication. Materials and Methods: In order to determine whether this increasing incidence in the UOQ is an artifact of different study populations or is chronological, data have been analysed for annual quadrant incidence of female breast cancer recorded nationally in England and Wales between 1979 and 2000 and in Scotland between 1980 and 2001. Results: In England and Wales, the recorded incidence of female breast cancer in the UOQ rose front 47.9% in 1979 to 53.3% in 2000, and has done so linearly over tune with a con-elation coefficient R of +/- 0.71 +/- SD 0.01 (p < 0.001). Analysis of independent data front Scotland showed a similar trend in that recorded female breast cancer had also increased in the UOQ from 38.3% in 1980 to 54.7% in 2001, with a con-elation coefficient R for the linear annual increase of +0.80 +/- SD 0.03 (p < 0.001). Conclusion: These results are inconsistent with current views that the high level of UOQ breast cancer is due solely to a greater amount of target epithelial tissue in that region. Identification of the reasons for such a disproportionate site-specific increase could provide clues as to causative factors in breast cancer.