Summary Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supematant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.Keywords: VEGF; breast cancer, oestradiol; progesterone; timing of surgery TIhe controversy of the timing of surgical intervention in premenopausal breast cancer patients was initiated when Hrushesky et al (1989). in a study of 44 patients. observed a better survival for tumours resected between days 7 and 20 of the menstrual cycle.Various studies follox%ed. with differing results. though four major studies have favoured the second half of the cycle. when the influence of progesterone predominates (Badwe et al. 1991;Senie et al. 1991: Veronesi et al. 1994: Goldhirsch et al. 1997.Angiogenesis has been shown to be essential for both the growth and metastasis of many solid tumours. with a large number of the data resulting from studies of breast cancer. In the absence of angiogenesis. a tumour will not grow beyond the size of 2-3 mm (Gimbrone et al. 1972 MATERIALS AND METHODSFourteen premenopausal women were recruited with no prior history of any breast disorders. None had any significant medical history. except one woman, who had ankylosing spondylosis.Three groups of controls were included: three post-menopausal women. one premenopausal woman on a low-dose oestrogen combined oral contraceptive pill and one male subject. Informed verbal consent was obtained from all subjects.Blood samples were taken at 4-day intervals in both the subjects and the controls. In the case of the premenopausal women, these were taken from day 1 of one menstrual cycle through to day 1 of the following cycle (8-11 samples per person). Two extra periovulatory samples were taken in four premenopausal women: thus. a total of 123 samples were taken from the premenopausal women. 65 in the follicular phase and 58 in t...
not available at time of publication. Abstract not available at time of publication. Retrospective studies on male breast cancer (MBC) have suff ered from small numbers of cases available from any one centre; thus a signifi cant problem in eff ectively studying this disease is accruing suffi ciently large numbers to allow comparative analysis of biomarkers associated with response. Using a coordinated multicentre approach, we present the fi rst large-scale study to address the relevance of the expression of hormone receptors in MBC and female breast cancer (FBC) using immunohistochemistry combined with a novel bioinformatics approach. Following ethical approval, 523 archival blocks (260 MBCs and 263 matched FBCs) were obtained retrospectively. Tissue microarrays were constructed and sections stained for ERα, ERβ1, ERβ2, ERβ5, total PR, PRA, PRB and AR and typed using CK5/6, CK14, CK18 and CK19 by immunohistochemistry. Following scoring, a range of ordination techniques were conducted on the datasets including hierarchical clustering and principal component analysis (PCA) + ) were infrequent in both. Hierarchical clustering revealed common clusters between MBC and FBC including total PR-PRA-PRB and ERβ1/2 clusters. ERα occurred on distinct clusters between males and females. AR, ERβ1, ERβ2 and ERβ5 all existed on the same cluster but with a diff erent substructure, particularly around the positioning of AR. ERα associated with this cluster in the male but not the female group. PCA confi rmed that in both groups strong infl uences came from PR-PRA-PRB. In MBC strong infl uences additionally came from AR and ERβ1, ERβ2 and ERβ5, whereas in FBC strong infl uences came from ERα alone. Our data support the hypothesis that breast cancer is biologically diff erent in male and females, which could have implications for therapy. Introduction The response rarely sustains long among the responders for Herceptin (trastuzumab) monotherapy treatment. It is still poorly understood how Herceptin exerts its mechanism of action and how the acquired resistance to this drug occurs. Materials and methods We used a multidisciplinary approach including fl uorescence resonance energy transfer and biochemical methods to assess the eff ects of Herceptin on various signalling pathways and to determine the acquired resistance mechanisms of Herceptin in various HER2-positive breast cell lines and a BT474 xenograft model. Results We have shown that Herceptin does not decrease HER2 phosphorylation despite the eff ect on HER2 receptor downregulation. HER2 phosphorylation is maintained by the activation of EGFR, HER3 and HER4 via their dimerisation with HER2 in breast cancer cells. The activation of EGFR, HER3 and HER4 is induced by HER ligand release, including heregulin and betacellulin. The release of HER ligands is mediated by ADAM proteases including ADAM17/TACE. Furthermore, we demonstrated that the feedback loop involving HER ligands and ADAM proteases is activated due to a decrease in PKB phosphorylation induced by Herceptin t...
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