Age at first birth and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

An early age at first full-term birth is associated with a reduction in the subsequent development of breast cancer among women in the general population. A similar effect has not yet been reported among women who carry an inherited BRCA1 or BRCA2 mutation. We conducted a matched case-control study on 1816 pairs of women with a BRCA1 (n = 1405) or BRCA2 (n = 411) mutation in an attempt to elucidate the relationship between age at first full-term pregnancy and the risk of developing breast cancer. Information about the age at first childbirth and other pregnancy-related variables was derived from a questionnaire administered to women during the course of genetic counselling. There was no difference in the mean age at first full-term birth in the cases and controls (24.9 years vs. 24.8 years; P = 0.81, respectively). Compared to women whose first child was born at or before 18 years of age, a later age at first full-term birth did not influence the risk of developing breast cancer (OR = 1.00 per year; 95% CI 0.98-1.03; P-trend = 0.67). Stratification by mutation status did not affect the results. These findings suggest that an early first full-term birth does not confer protection against breast cancer in BRCA mutation carriers. Nonetheless, BRCA mutation carriers opting for a prophylactic oophorectomy as a breast and/or ovarian cancer risk-reducing strategy should complete childbearing prior to age 40 when this prevention modality is most effective.

Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial.

OBJECTIVE: To assess the effects of a comprehensive change in dietary composition on endogenous hormone metabolism. The specific aim was to examine whether this intervention could lead to favourable changes in insulin sensitivity, levels of IGF-I and IGF-binding proteins (IGFBPs), and total and bioavailable testosterone and estradiol, that would be expected to reduce breast cancer risk. DESIGN: Randomised dietary intervention study; duration of 5 months. SUBJECTS: From a total of 99 postmenopausal women, who had elevated baseline plasma testosterone levels, 49 women were randomly assigned to the dietary intervention arm and the other 50 to a control group. INTERVENTIONS: Main aspects of the dietary intervention were reductions in the intake of total fat and refined carbohydrates, an increase in the ratio of n-3 over n-6 plus saturated fatty acids, and increased intakes of foods rich in dietary fibre and phytooestrogens. RESULTS: Relative to the control group, women of the intervention group showed a significant reduction of body weight, waist circumference, fasting serum levels of testosterone, C peptide, glucose, and insulin area after glucose tolerance test, and a significant increase of serum levels of sex hormone-binding globulin, IGFBP-1, -2, and growth hormone-binding protein. Serum levels of IGF-I did not change. CONCLUSION: This comprehensive dietary intervention strategy proved to be successful in inducing changes in endogenous hormone metabolism that might eventually result in reduced breast cancer risk. Additional studies are needed to show whether the dietary intervention and related hormonal changes can be both maintained over longer periods, of at least several years.

Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.

High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer.

High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women.

OBJECTIVE: The purpose of this study was to determine if there is an association between elevated sex hormones (ie, serum estradiol, sex hormone binding globulin [SHBG], testosterone) and increased venous distension and clinical evidence of varicose veins in menopausal women. METHODS: Participants were 104 healthy volunteer menopausal women, aged 48 to 65 years, who were not undergoing hormonal treatment. Of these 104, 14 were excluded from analyses because their estradiol levels were compatible with a premenopausal condition (4), because they had missing values for insulin concentration (5), and because they did not show up at venous vessel examination (5). Patients underwent a physical examination to determine the presence of varicose veins; a venous strain-gauge plethysmographic examination to compute instrumental measures of venous distensibility; and laboratory analyses of blood so serum testosterone, estradiol, SHBG, glucose, and insulin could be measured. There were also prevalence ratios and odds ratios used to test the presence of an association between biochemical and instrumental variables. RESULTS: Serum levels of estradiol in the upper tertile of the frequency distribution were significantly associated with clinical evidence of varicose veins (prevalence odds ratios 3.6; 95% CI 1.1-11.6) and with increased lower limb venous distensibility (prevalence odds ratios 4.4; 95% CI 1.2-15.5). No association was found for SHBG and testosterone. CONCLUSIONS: Our finding that high serum levels of estradiol are associated with clinical evidence of varicose veins and instrumental measurements indicating increased venous distensibility in menopausal women suggests that endogenous estrogens may play a role in the development of this very common venous vessel abnormalities.

[Diet, hormones, genes, and breast cancer]. / Dieta, ormoni, geni e cancro della mammella.

The review describes on-going studies at the Unit of cancer epidemiology of the National Cancer Institute in Milan-Breast carcinogenesis is reviewed addressing: 1) Hormones and breast cancer 2) Diet and breast cancer 3) Diet and hormones 4) Potentiality of dietary prevention in women at high genetic risk.