Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: Pooled individual data analysis of 17 prospective studies

Background: Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk. Methods: Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0\ub705 was considered significant. Findings: IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1\ub728 (95% CI 1\ub714-1\ub744; p<0\ub70001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1\ub738 (95% CI 1\ub714-1\ub768) for oestrogen-receptor-positive tumours and 0\ub780 (0\ub757-1\ub713) for oestrogen-receptor-negative tumours (p for heterogeneity=0\ub7007). Interpretation: Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours

ZEN and the art of breast health maintenance

Zearalenone (ZEN) is a non-steroidal mycoestrogen that widely contaminates agricultural products. ZEN and its derivatives share similar molecular mechanisms and activity with estrogens and interact with ERα and ERβ leading to changes in the reproductive system in both animals and humans. The reduced form of ZEN, α-ZEA ralenol, has been used as an anabolic agent for animals and also proposed as hormonal replacement therapy in postmenopausal women. Furthermore, both zearelanol ZEN and derivatives have been patented as oral contraceptives. ZEN has been widely used in the United States since 1969 to improve fattening rates in cattle by increasing growth rate and feed conversion efficiency. Evidence of human harm from this practice is provided by observations of central precocious puberty. As a result, this practice has been banned by the European Union. As ZEN has been associated with breast enlargement in humans, it has been included in many bust-enhancing dietary supplements but epidemiological evidence is lacking with regard to breast cancer risk. Extensive work with human breast cancer cell lines has shown estrogenic stimulation in those possessing ER but a reduction in DMBA-induced breast cancers in rodents given ZEN. Protein disulfide isomerase provides a molecular biomarker of dietary exposure to ZEN and its derivatives allowing the detection and control of harmful food intake. The interaction of ZEN with anti-estrogens, anticancer agents and antioxidants requires further investigation. © 2011 Blackwell Publishing Ltd

The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable interest as potential chemopreventive agents. The aim of this review is to summarize the accumulated knowledge on the effect of NSAIDs on breast cancer incidence and natural history, and the underlying pathophysiology. NSAIDs mainly block inflammation by inhibiting cyclooxygenase enzymes, leading to lower prostaglandin synthesis. The latter has been reported to affect breast cancer risk through hormonal and inflammation-related pathways. Intensity, dose, frequency, duration, and timing of administration may also be significant. There is currently enough evidence to support a role of NSAIDs in breast cancer prevention and relapse, which deserves further large-scale experimental and clinical investigation. © 2016 S. Karger GmbH, Freiburg

Electropotential evaluation as a new technique for diagnosing breast lesions

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