Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

BACKGROUND: Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. PATIENTS AND METHODS: In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. RESULTS: ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. CONCLUSIONS: We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

A comparison of hormonal profiles between breast cancer and benign breast disease: a case-control study.

BACKGROUND: Benign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case-control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology. PATIENTS AND METHODS: We studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD). RESULTS: The hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD. CONCLUSIONS: Our findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.

The hormonal profile of benign breast disease.

BACKGROUND: Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology. METHODS: We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires. RESULTS: Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (-4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (-5.0%, 42.9%) for testosterone; and -5.2% (-13.8%, 4.4%) and -12.1% (-19.8%, -3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD. CONCLUSIONS: Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.