Androgen excess in breast cancer development: implications for prevention and treatment.

The aim of this review is to highlight the pivotal role of androgen excess in the development of breast cancer. Available evidence suggests that testosterone controls breast epithelial growth through a balanced interaction between its two active metabolites: cell proliferation is promoted by estradiol while it is inhibited by dihydrotestosterone. A chronic overproduction of testosterone (e.

Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy.

Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment.

A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer.

Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers.

Background: Androgen receptors (AR) are frequently expressed in breast cancers, but their implication in cancer growth is still controversial. In the present study, we further investigated the role of the androgen/AR pathway in breast cancer development.

Methods: AR expression was evaluated by immunochemistry in a cohort of 528 postmenopausal breast cancer patients previously examined for the association of serum testosterone levels with patient and tumor characteristics.

Role of androgen excess in the development of estrogen receptor-positive and estrogen receptor-negative breast cancer.

The androgen-excess theory posits a central role of androgens in promoting breast cancer development. At first glance, this appears to contradict the currently accepted central role of estrogens in this process, but as we will show, the apparent contradiction is not a real one. In the present article, we review the mechanisms by which androgen excess may stimulate cancer growth in different subsets of estrogen receptor-positive and estrogen receptor-negative tumors.

Influence of fatty acid-free diet on mammary tumor development and growth rate in HER-2/Neu transgenic mice.

Numerous investigations have found a relationship between higher risk of cancer and increased intake of fats, while results of clinical studies of fat reduction and breast cancer recurrence have been mixed. A diet completely free of fats cannot be easily administered to humans, but experimental studies in mice can be done to determine whether this extreme condition influences tumor development. Here, we examined the effects of a FA-free diet on mammary tumor development and growth rate in female FVB-neu proto-oncogene transgenic mice that develop spontaneous multifocal mammary tumors after a long latency period.

Circulating sex hormones and tumor characteristics in postmenopausal breast cancer patients. A cross-sectional study.

Background: To further investigate the role of sex hormones in breast cancer, we assessed the relations of circulating estradiol and testosterone to tumor size and estrogen receptor (ER) status.

Method: This was a cross-sectional study including 492 postmenopausal breast cancer patients. The relation of circulating hormones to patient and tumor characteristics was assessed using the Fisher or Cuzick tests.

Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility.

Single-nucleotide polymorphisms (SNP) associated with polygenetic disorders, such as breast cancer (BC), can create, destroy, or modify microRNA (miRNA) binding sites; however, the extent to which SNPs interfere with miRNA gene regulation and affect cancer susceptibility remains largely unknown. We hypothesize that disruption of miRNA target binding by SNPs is a widespread mechanism relevant to cancer susceptibility. To test this, we analyzed SNPs known to be associated with BC risk, in silico and in vitro, for their ability to modify miRNA binding sites and miRNA gene regulation and referred to these as target SNPs.

Urinary 6-Sulphatoxymelatonin levels and risk of breast cancer in premenopausal women: the ORDET cohort.

Background: Lower urinary melatonin levels are associated with a higher risk of breast cancer in postmenopausal women. Literature for premenopausal women is scant and inconsistent.

Methods: In a prospective case-control study, we measured the concentration of 6-sulphatoxymelatonin (aMT6s) in the 12-hour overnight urine of 180 premenopausal women with incident breast cancer and 683 matched controls.

Testosterone and biological characteristics of breast cancers in postmenopausal women.

Androgens are involved in the development of breast cancer, although the mechanisms remain unclear. To further investigate androgens in breast cancer, we examined the relations between serum testosterone and age, body mass index (BMI), tumor size, histologic type, grade, axillary node involvement, estrogen receptor status, progesterone receptor status, and HER2 overexpression in a cross-sectional study of 592 postmenopausal breast cancer patients. Mean testosterone differences according to categories of patient and tumor characteristics were assayed by Fisher's or Kruskall-Wallis test as appropriate; adjusted odds ratios (OR) of having a tumor characteristic by testosterone tertiles were estimated by logistic regression.

Bilateral breast cancer in a male patient with hepatocellular carcinoma. A case report.

Male breast cancer accounts for about 1% of all breast cancers and bilateral breast cancer in men is therefore a rare event. Data in literature indicate that approximately 20% of these tumours are due to a probable alteration in the oestrogen metabolism. Hepatocellular carcinoma (HCC) on the other hand, is a much more frequent tumour and in 70-80% of cases is associated with cirrhosis.

Serum insulin-like growth factor-I and platelet-derived growth factor as biomarkers of breast cancer prognosis.

Epidemiologic studies have shown that growth factors and inflammatory mechanisms may affect breast cancer risk and prognosis. The present analysis on 110 postmenopausal breast cancer patients tested if serum insulin-like growth factor I (IGF-I), platelet-derived growth factor (PDGF), fructosamine, and C-reactive protein, a serum marker of inflammation, are associated with breast cancer relapse. The risk of adverse events after 5.

Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women.

Background: Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women. However, the association between melatonin levels and breast cancer risk in postmenopausal women remains unclear.

Methods: We investigated the association between melatonin levels and breast cancer risk in postmenopausal women in a prospective case-control study nested in the Hormones and Diet in the Etiology of Breast Cancer Risk cohort, which included 3966 eligible postmenopausal women.

Immune and endocrine mechanisms of advanced cancer-related hypercortisolemia.

Background: Cancer progression depend on the immune and endocrine status of the patients. In particular, it has been observed that abnormally high levels of cortisol and/or an altered circadian secretion are associated with a poor prognosis in advanced cancer patients. The present study was performed to establish whether cancer-induced hypercortisolemia depends on an activation of the hypothalamic-pituitary axis or on a direct adrenal stimulation by inflammatory cytokines, such as IL-6, which have been proven to induce cortisol secretion.

Plasma testosterone and prognosis of postmenopausal breast cancer patients.

Purpose: High endogenous testosterone is associated with increased breast cancer (BC) risk. We designed this study specifically to assess the long-term prognostic role of testosterone in a cohort of postmenopausal BC patients.

Patients And Methods: We considered 194 postmenopausal women, operated on for early BC (T1-2N0M0), who never received chemotherapy or hormonal therapy, and who participated in a fenretinide BC prevention trial as untreated controls.

Reliability of urinary 6-sulfatoxymelatonin as a biomarker in breast cancer.

The objective of this study is to evaluate the effect of cryopreservation at different storage temperatures on urinary 6-sulfatoxymelatonin (aMT6s) concentration. Overnight urine from 28 postmenopausal women participating in the ORDET cohort study was filtered and separated into 6 mL aliquots. Urine samples were stored at -80 degrees C and at -30 degrees C for an average of 14 years.

Plant-based diet, serum fatty acid profile, and free radicals in postmenopausal women: the diet and androgens (DIANA) randomized trial.

High calorie and fat consumption and the production of free radicals are two major mechanistic pathways between diet and disease. In this study we evaluated the effect of a plant-based diet poor in animal fat and rich in (n-3) fatty acids on fatty acids of serum phospholipids and on the production of reactive oxygen metabolites (ROMs). One hundred and four healthy female postmenopausal volunteers were recruited and randomized to a dietary intervention or a control group.

Evaluation of reactive oxygen metabolites in frozen serum samples. Effect of storage and repeated thawing.

Measuring the free radical activity in serum samples from prospective studies is the best way to investigate the association between oxidative stress and human diseases. Prospective studies require the analysis of serum samples that have often been stored for a long time. Our study was designed to determine the effect of storage at -30 degrees C and -80 degrees C for two years on free radical activity.

Serum testosterone levels and breast cancer recurrence.

Prospective studies show that high serum levels of androgens and estrogens are associated with increased incidence of postmenopausal breast cancer. The aim of the present analysis was to study the prognostic value of serum testosterone, estradiol and related factors in postmenopausal breast cancer patients. One hundred and ten patients without clinical recurrence were included in the study.

Endogenous sex hormones and subsequent breast cancer in premenopausal women.

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle.

Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study.

Objective: To evaluate the effect of soy isoflavones and melatonin in relieving menopausal symptoms.

Methods: Double-blind, multicenter, randomized trial performed according to a 2 x 2 factorial design. Treatment groups: (1) soy isoflavones+melatonin; (2) soy isoflavones alone; (3) melatonin alone; (4) placebo.

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.