Are mammotropic hormones mainly permissive for the development of breast cancer?

Abstract

In a case-control study nested within the Greek EPIC cohort, serum levels of estrone, estradiol, androstenedione, dehydroepiandosterone sulfate, testosterone and IGF-1 were measured for 29 breast cancer patients and 58 control women, matched for age and menopausal status. There was little difference in breast cancer risk when values of 4-6-as compared to values of 1-3-hormones were elevated, a finding arguing against a positive interaction among these hormones. Breast cancer risk, however, was significantly and substantially lower among women with levels of all hormones below the corresponding age-and menopausal-status-predicted means, compared to women with levels of at least 1 hormone above the predicted mean (odds ratio 5 0.11 with 95% confidence interval 0.01-0.90; p 5 0.04). Our results suggest that the studied mammotropic hormones may act as permissive factors for breast cancer occurrence, and that the levels of some of them above the mean suffice for sustaining growth of a developing tumor. A corollary is that studies of mammotropic hormones in relation to breast cancer risk may also need to focus on the lower end of the distributions of these growth-enhancing hormones. ' 2005 Wiley-Liss, Inc.

Nested Case-Control Study of the Association of Circulating Levels of Serum Insulin-like Growth Factor I and Insulin-like Growth Factor Binding Protein 3 with Breast Cancer in Young Women in Norway

“…The consistent increase in risk that we observed with decreasing levels of IGFBP-3 seems to be biologically plausible, but the statistical evidence for this association was weak (P = 0.12). Nonetheless, our results seem to be compatible with a permissive role of IGF-I, as previously suggested (22). In this large study among young women, only a modest positive association between IGF-I and breast cancer risk was observed.…”

The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: a nested case-control study

“…The first goal of this study was to replicate the analysis by Trichopoulos et al [9], thus we created a score that was the sum of the number of hormones for each woman above the age- and batch-adjusted mean level. The results derived using the median were similar and therefore are not shown.…”

“…For example, compared to women with low IGF-1 and low testosterone levels, those with high levels of both had a RR = 2.2 (95% CI = 1.0 to 4.5) versus a RR = 1.7 (95% CI = 0.8 to 3.6) for high testosterone only or a RR = 1.1 (95% CI = 0.5 to 2.4) for IGF-1 only. Only one small study (29 cases and 58 controls) considered more than two hormones at the same time [9]. Estrone, estradiol, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and IGF-1 were measured on prospectively collected serum samples.…”

“…We created a hormone score similar to that described by Trichopoulos et al [9], as well as scores based on other approaches, including weighting hormone values by their individual association with breast cancer risk or by their proliferative effect on breast cancer cell lines. On the basis of prior data indicating that sex hormones tend to be more strongly associated with estrogen receptor (ER)-positive disease [2,5,6], we evaluated the scores for this subset of tumors.…”

Early life events and conditions and breast cancer risk: From epidemiology to etiology

“…An important issue that has not been sufficiently explored in empirical research is the way these hormones interact in the causation of the disease. A small study presented evidence that mammotropic hormones may act as permissive factors for breast cancer occurrence and that values of any one of these above a certain level may suffice for sustaining growth of a developing tumor 66 -the finding is intriguing but requires confirmation in larger datasets. The second component of the etiologic model accommodates our knowledge about the role of reproductive factors in the etiology of the disease as well as that of alcohol drinking (which tends to increase oestrogen levels), physical activity and adult life diet.…”