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.

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.

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.

Contribution of highly industrially processed foods to the nutrient intakes and patterns of middle-aged populations in the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVES: To describe the contribution of highly processed foods to total diet, nutrient intakes and patterns among 27 redefined centres in the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Single 24-hour dietary recalls were collected from 36,034 individuals (aged 35-74 years) using a standardized computerized interview programme (EPIC-SOFT). Centre-specific mean food intakes (g/day) were computed according to their degree of food processing (that is, highly, moderately and non-processed foods) using a specifically designed classification system. The contribution (%) of highly processed foods to the centre mean intakes of diet and 26 nutrients (including energy) was estimated using a standardized nutrient database (ENDB). The effect of different possible confounders was also investigated. RESULTS: Highly processed foods were an important source of the nutrients considered, contributing between 61% (Spain) and 78-79% (the Netherlands and Germany) of mean energy intakes. Only two nutrients, beta-carotene (34-46%) and vitamin C (28-36%), had a contribution from highly processed foods below 50% in Nordic countries, in Germany, the Netherlands and the United Kingdom, whereas for the other nutrients, the contribution varied from 50 to 91% (excluding alcohol). In southern countries (Greece, Spain, Italy and France), the overall contribution of highly processed foods to nutrient intakes was lower and consisted largely of staple or basic foods (for example, bread, pasta/rice, milk, vegetable oils), whereas highly processed foods such as crisp bread, breakfast cereals, margarine and other commercial foods contributed more in Nordic and central European centres. CONCLUSIONS: Highly industrially processed foods dominate diets and nutrient patterns in Nordic and central European countries. The greater variations observed within southern countries may reflect both a larger contribution of non/moderately processed staple foods along with a move from traditional to more industrialized dietary patterns.