Hormonal profiles and estrogen receptors in Egyptian female breast cancer patients

AIMS AND BACKGROUND: Hormones are considered to be an important factor in the etiology of breast cancer. Serum hormonal profiles of premenopausal and postmenopausal breast cancer patients as well as estrogen receptor (ER) concentrations in breast cancer tissues were examined in an attempt to establish a possible association between hormones and breast cancer risk and to elucidate the biological features of the disease among Egyptian female patients. METHODS: Levels of estradiol (E2), testosterone (T), progesterone (P), LH, FSH, prolactin, T3, T4 and TSH were measured by highly specific radioimmunoassays in the sera of women with breast cancer and compared to those of control subjects. ER concentrations in breast tumor tissues were measured using 125I-radioreceptor assay. RESULTS: Levels of T and prolactin showed a significant increase in both premenopausal and postmenopausal patients. E2 and P levels were significantly increased in follicular premenopausal and postmenopausal patients. Luteal E2 showed non-significant changes, whereas the luteal P level was significantly decreased. No significant alterations were found in the levels of serum LH, FSH, T3, T4 and TSH either in premenopausal or postmenopausal patients. Higher levels of ER were found in the tumors of postmenopausal than in those of premenopausal patients. A positive correlation was found between levels of ER and age of the patients (r = 0.35), whereas a negative correlation was observed between ER and serum E2 (r = -0.26). CONCLUSIONS: This study provides evidence of an association between high levels of serum E2 and T and increased risk of breast cancer in postmenopausal women. Abnormalities in serum P and prolactin are probably associated with a breast cancer risk and ER may be considered as a biochemical marker for breast cancer development.     

Serum levels of sex hormones and breast cancer risk in premenopausal women: a case–control study (USA)

High levels of serum estrogens and androgens have been convincingly linked with an increased risk of breast cancer among postmenopausal women. By contrast, the role of blood levels of these hormones in the etiology of premenopausal breast cancer is not well understood. In a case-control study, we sought to examine associations between levels of serum estradiol, sex-hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), testosterone, androstenedione and progesterone and risk of premenopausal breast cancer. Cases of breast cancer under age 45 were identified using rapid ascertainment systems in Seattle/Puget Sound, Washington and control subjects were identified from the same area through random digit dialing methods. A total of 169 eligible breast cancer cases and 195 control subjects donated blood (either before or six or more weeks after surgery) and were interviewed using a standardized questionnaire. The fully adjusted risk ratios and 95% confidence intervals for the highest versus lowest tertiles of estradiol, according to menstrual cycle phase, were 3.10 (0.8-12.7) for early follicular, 0.54 (0.2-1.7) for late follicular and 0.60 (0.3-1.4) for luteal. Risks for highest versus lowest quartiles of SHBG and androgens were 0.81 (0.4-1.6) for SHBG, 2.42 (1.1-5.2) for DHEA, 1.12 (0.6-2.5) for testosterone, and 1.33 (0.6-2.8) for androstenedione. For luteal progesterone, the RR for the highest versus lowest tertile was 0.55 (0.2-1.4). In summary, we did not find a convincing association between serum SHBG, estradiol, testosterone or androstenedione and premenopausal breast cancer risk. Observed differences between cases and controls subjects in serum levels of DHEA and luteal phase progesterone should be investigated further in large prospective studies.     

Plasma lipids in premenopausal women with mammographic dysplasia.

Epidemiological evidence indicates that mammographic dysplasia is associated with an increased risk of breast cancer, particularly in premenopausal women. To examine biochemical associations with mammographic dysplasia we have compared premenopausal women with different patterns of the breast parenchyma on mammography. One group had extensive radiological dysplasia (n = 30) and the other no dysplasia (n = 16). Both groups were recruited from mammographic units in the same way and then compared according to epidemiological risk factors, anthropometric measures, nutrient intake and plasma levels of oestradiol, progesterone and prolactin obtained in both follicular and luteal phases of the menstrual cycle as well as total plasma cholesterol and lipid fractions. Women with mammographic dysplasia were found to be leaner, more often nulliparous and to consume more alcohol than women without these radiological changes. Mammographic dysplasia and a family history of breast cancer were found to be independently associated with significantly higher levels of high density lipoprotein cholesterol (HDL-C) after taking into account the possible confounding effects of percentage body fat, parity and consumption of alcohol and dietary fat. Triglyceride levels were also independently associated with a family history of breast cancer. We conclude that further investigation is warranted of the role of plasma lipids in relation to breast cancer risk.     

Effect of letrozole on the lipid profile in postmenopausal women with breast cancer

Hormonal therapy plays a central role in the overall treatment of breast cancer. Aromatase inhibitors can inhibit the aromatase enzyme system resulting in a reduction of oestrogens. Letrozole is a non-steroidal aromatase inhibitor that effectively blocks aromatase activity without interfering with adrenal steroid biosynthesis. The drug can significantly reduce the levels of plasma oestrogens, which remain suppressed throughout the treatment. Data are scarce concerning the influence of these drugs on serum lipid levels. In the present study, we evaluated the effects of letrozole on the serum lipid profile in postmenopausal women with breast cancer. A total of 20 patients with breast cancer were treated with letrozole, 2.5 mg once daily. After an overnight fast, serum lipid parameters (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, apolipoproteins A1, B and E and lipoprotein (a)) were measured before treatment and at 8 and 16 weeks afterwards. A significant increase in total cholesterol (P=0.05), LDL cholesterol (P<0.01) and apolipoprotein B levels (P=0.05) in the serum, as well as in the atherogenic risk ratios total cholesterol/HDL cholesterol (P<0.005) and LDL cholesterol/HDL cholesterol (P<0.005) was noticed after letrozole treatment. We conclude that letrozole administration in postmenopausal women with breast cancer has an unfavourable effect on the serum lipid profile.     

Obesity, serum cholesterol, and estrogens in premenopausal women

Creatinine-adjusted levels of estrone, estradiol, and estriol were determined in luteal phase urine specimens of 200 premenopausal women from rural areas of Greece. The relation of each estrogen to height, weight, obesity index, and serum cholesterol was studied by multiple regression, controlling for age, age at menarche, and ovulation status (ovulation, anovulation, undetermined). No consistent relation between any of the somatometric variables and any of the urine estrogens emerged from the statistical analysis, but among older women (30-40 years old) both estrone and estradiol were positively associated with serum cholesterol (p less than 0.05). The data provide no support for the hypothesis that the relationship between body weight and breast cancer risk is mediated through an influence of body weight on estrogen levels--at least in premenopausal women. On the other hand the data on serum cholesterol levels are consonant with the idea that qualitative aspects of nutrition may affect breast cancer risk among older (e.g., postmenopausal) women.     

Risk of breast cancer in relation to anthropometry, blood pressure, blood lipids and glucose metabolism: a prospective study within the Malm? Preventive Project.

Insulin resistance may be a risk factor for breast cancer, possibly through increased levels of oestrogens or insulin-like growth factor I. Insulin resistance has been associated with obesity, hypertension, dyslipidaemia and impaired glucose tolerance. We studied the relation of these factors to breast cancer risk in a prospective cohort study of 9738 women. Menopausal status was defined a priori, and 112 cases of invasive breast carcinoma occurred in women who were premenopausal at baseline and 157 cases in subjects who were peri/postmenopausal. Relative risks (RR) for breast cancer were calculated by Cox's proportional hazards analysis for different quartiles of height, weight, body mass index, blood pressure, pulse rate and serum levels of total cholesterol, triglycerides, fasting blood glucose and glucose at 120 min after an oral dose of glucose. Peri/postmenopausal women had a significantly increased age-adjusted relative risk of breast cancer associated with height (RR = 1.78 for the highest versus lowest quartile), and the RR was increased over quartiles of cholesterol levels (P-value for trend: 0.05). No other significant associations were found. Adjustments for potential confounding factors or restriction of the analysis to cases and person-years before 55 years of age (premenopausal women), or after 55 years (peri/postmenopausal women), did not change     

Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Nutritional and metabolic aspects

Intake of vitamin E, total lipids, total cholesterol, and fatty acids were analyzed with the blood levels of vitamin E, total cholesterol, triglycerides, and the serum distribution of fatty acids in a hospital-based population of 120 patients and 109 controls. In regard to nutritional intake, the only significant differences involve saturated and monounsaturated fatty acid consumption, which is more elevated in postmenopausal patients than in postmenopausal controls. Vitamin E and total cholesterol blood levels are significantly higher in patients than in controls, where the difference is that vitamin E is independent from cholesterol level in premenopausal women only. Fatty acid serum distribution is comparable in both samples, with the exception of arachidonic acid, which is significantly lower in premenopausal patients than in premenopausal controls. Two multivariate regression analyses of the plasma vitamin E levels of patients and controls were done with menopausal status and nutrients as independent variables for the first analysis, and with menopausal status and all blood analytes for the second one. The regression coefficients for total cholesterol and triglycerides are statistically significant for both samples, whereas a positive association between vitamin E plasma level and sunflower oil consumption and between vitamin E plasma level and serum linoleic acid distribution is significant for patients only. Furthermore, the multiple regression shows that, when adjusted for analyte variables, plasma vitamin E levels are higher in premenopausal than in postmenopausal patients. In addition, plasma lipid peroxidation, evaluated by malondialdehyde measurement, is shown to be significantly lower in patients than in controls. Malondialdehyde level is associated with a significant lower odds ratio (OR) after multivariate tertile analysis (OR for the highest tertile: 0.51; 95% CI: 0.29-0.89). Together, these findings are consistent with a picture of lower lipid peroxidation in patients than in controls.     

Duration of tamoxifen effect on lipidemic profile of postmenopausal breast cancer patients following deprivation of treatment

OBJECTIVE: It was the aim of this study to investigate the effect of tamoxifen withdrawal on markers of lipid metabolism in postmenopausal women with breast cancer who completed tamoxifen therapy and received no further treatment. METHODS: Lipidemic profile changes were studied in 190 postmenopausal patients with operable breast cancer, following cessation of 5-7 years of tamoxifen treatment. Assessments of total cholesterol, high-density lipoprotein, low-density lipoprotein and total serum triglycerides were performed at baseline, 6 months and 12 months. RESULTS: By 6 months, both total cholesterol and low-density lipoprotein levels were significantly increased, and total triglyceride levels were significantly reduced compared with baseline values and maintained to 12 months. There was no significant alteration observed for high-density lipoprotein levels over the study period. CONCLUSION: The beneficial effect of tamoxifen on the lipidemic profile of postmenopausal breast cancer patients seems to be lost in less than 12 months time following cessation of 5-7 years of tamoxifen treatment. A 'rebound effect' on the lipidemic parameters should be expected and those patients should be monitored carefully.     

Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer

We conducted a 2-year, randomized, double-blind, placebo-controlled toxicity trial of therapy with tamoxifen (10 mg twice a day) in 140 postmenopausal women with a history of breast cancer and histologically negative axillary lymph nodes. These women had been treated with surgery with or without radiotherapy. At a 3-month evaluation, tamoxifen-treated women showed a significant decrease in fasting plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which persisted at 6- and 12-month evaluations. During the first 12 months, plasma triglyceride levels increased; small but significant decreases in high-density lipoprotein cholesterol (HDL) were observed in tamoxifen-treated women, but ratios of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol changed favorably. While data relating lipid/lipoprotein profiles and cardiovascular disease are limited in women, current evidence suggests that total cholesterol and possibly low-density lipoprotein cholesterol are risk factors. We conclude that during the first 12 months of treatment, tamoxifen exerts a favorable effect on the lipid profile in postmenopausal women with early stage breast cancer.     

Serum estrogen level in Egyptian breast cancer patients

In menstruating 20-29 year old breast cancer patients, the total estrogen level showed a significant increase in the early follicular phase compared to normal healthy subjects. Such a difference was not observed in 30-45 year-old patients. A nonsignificant decrease was observed in the estradiol level of premenopausal breast cancer patients compared to normal healthy subjects. However, in postmenopausal breast cancer patients, the total estrogen level as well as the estradiol level showed a significant increase compared to that of normal healthy subjects.     

Plasma lipids and prolactin in patients with breast cancer

In a comparative study of pre- and postmenopausal women with benign and malignant breast disease, a number of differences were observed in circulating plasma prolactin and lipid concentrations. Plasma lipids, phospholipids, triglycerides, cholesterol and free fatty acids were all higher in blood obtained from breast cancer patients prior to surgery. HDL-Cholesterol levels were significantly lower in these patients. These differences remained when the patient groups were sub-divided according to menopausal status. Plasma prolactin concentrations were also found to be higher in cancer compared with non-cancer patients, this effect being more marked in premenopausal than in postmenopausal patients. Premenopausal patients with invasive or poorly differentiated disease had significantly higher prolactin levels than those with non-invasive disease. No correlations were found between plasma prolactin and any of the lipid fractions.     

阿那曲唑对绝经后乳腺癌患者血脂的影响

目的 观察阿那曲唑辅助治疗对中国绝经后乳腺癌患者血脂代谢的影响及其他不良反应.方法 需要术后辅助内分泌治疗的绝经后乳腺癌患者285例,给予阿那曲唑1 mg,1次/d,分别检测其服药前及服药后3个月、6个月、1年、2年、3年、4年和5年的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)水平.电话随访服药过程中出现的其他不良反应.结果 285例患者的中位服药时间为3.6年.服药6个月后即导致LDL-C升高,持续至服药后第5年,其中服药后第4年最高,为(3.64±0.96)mmol/L,较服药前[(3.08±0.90)mmol/L]升高18.2%.服药1年后,TC和HDL-C开始升高,并持续至服药后第4年,TG无明显变化.亚组分析显示,对于服药前伴有高血脂的患者,除服药后1年出现TC升高(随后恢复)外,阿那曲唑对高血脂患者的血脂无明显影响;相对于＜60岁的患者,阿那曲唑对于年龄≥60岁患者的血脂影响更明显.服药过程中出现的其他不良反应包括潮热、骨关节疼痛、烦躁、恶心呕吐、腹泻、乏力、阴道干燥、体重增加、阴道出血、骨折、皮疹等,均较轻微,患者可耐受.结论 绝经后乳腺癌患者术后接受阿那曲唑辅助内分泌治疗,可导致血脂代谢的变化,主要表现为TC、LDL-C、HDL-C升高,尤其对于年龄≥60岁的患者影响更加明显.建议长期口服阿那曲唑的患者定期复查血脂.其他不良反应轻微,患者可耐受.

Abstract：

Objective The aim of this study was to evaluate the effect of anastrozole, a new generation aromatase inhibitor, on the lipid metabolism in postmenopausal Chinese women with early breast cancer, and observe the adverse reactions as well. Methods Postmenopausal women with early breast cancer patients took anastrozole 1 mg per day. The lipid profiles of total cholesterol, triglyceride, low density lipoprotein, and high density lipoprotein were assessed before taking the drug, 3 months, 6 months after taking medication, and later once a year, until the end of medication or follow-up. Patients taking lipid-lowering drugs were excluded. The adverse reactions during the process of taking medication was followed-up by telephone. Results Two hundred and eighty-five postmenopausal breast cancer patients took part in the trial from Jan. 2003 to Jun. 2009. All patients had completed primary surgery and demonstrated a postmenopausal status. ER or PR positivity was confirmed by histopathology. Taking the medication from a minimum of one year to a maximum of 5 years,with a median time of 3.61 years. During the medication time, anastrozole significantly increased the levels of low density lipoprotein-cholesterol after 6 months of treatment, continueing to 5 years, from (3.08±0.90)mmol/L to (3.59±0.59)mmol/L,with a maximal increase of 18.2% higher than that before medication. Anastrozole significantly increased the levels of total cholesterol and high density lipoprotein-cholesterol after 1 years of treatment. Anastrozole significantly reduced the levels of triglycerides after 1 years of treatment. Anastrozole showed no significant effect on serum lipids in the patients with pre-existing hyperlipidemia. A more significant effect on blood lipids was observed in patients aged ≥ 60-years than that in patients less than 60 years of age. The rate of other adverse events were similar to that reported in foreign patients. Conclusions For the postmenopausal patients with breast cancer, taking anastrozole may lead to an abnormal lipid metabolism. Anastrozole significantly increases the levels of low density lipoprotein-cholesterol, total cholesterol and high density lipoprotein-cholesterol, and significantly reduces the level of triglycerides. The rate of other adverse events were similar to that reported in foreign patients. it is suggested that the blood lipid levels should be regularly assessed in patients with long-term anastrozole treatment. The rate of other adverse events similar to that reported with foreign patients, and patients tolerate this treatment well.     

Tamoxifen in premenopausal patients with metastatic breast cancer: a review

The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration.     

Preoperative serum levels of follicle stimulating hormone (FSH) and prognosis in invasive breast cancer.

AIMS: We investigated the association between preoperative serum levels of follicle stimulating hormone (FSH) and the prognosis in women with invasive breast cancer. METHODS: Serum levels of FSH were measured in 182 premenopausal and 581 peri- or postmenopausal women with invasive breast cancer. They were followed for a mean time of 84 months. The study endpoint was death from breast cancer (182 events). Analyses were stratified on menopausal status. RESULTS: None of the estimates showed a statistically significant result. In both pre- and postmenopausal women there was a nominally higher probability of survival with a higher FSH level. Point estimates in multivariate analysis incorporating age, tumour diameter, axillary lymph status, estrogen and progesterone receptor content and year of treatment indicated a stronger association with FSH levels in premenopausal than postmenopausal women (relative hazard 0.63 or 0.85, respectively in the highest compared with the lowest quartile). CONCLUSION: We did not find any statistically significant association between preoperative serum level of FSH and prognosis. Today, FSH is not a clinical target for intervention or a clinically useful prognostic factor and the results of clinical studies up to date can only be used for motivation of further experimental laboratory research.     

Normal Breast Lobular Architecture in Breast Biopsy Samples From Breast Cancer Cases and Benign Disease Controls

Rodent studies suggest a relationship between lobular maturation and breast cancer risk. Human data are sparse, and were developed using whole mounts of mastectomy or mammoplasty samples, without consideration of menstrual phase in premenopausal women. We studied normal breast lobules in relation to cancer risk in 284 women, using surgical biopsy material (mean two sections and 43.2 lobular structures per subject): 167 were premenopausal; 89 with breast cancer (cases) and 78 undergoing benign breast biopsy (controls). Of 117 postmenopausal women, 67 were cases and 50 were controls. Normal lobular type was classified based on size, and was designated predominant if it constituted 60% or more of the total lobules classified. The control group showed 66% type I, 34% type II and 1% type III lobules while cases showed 69% type I, 31% type II and 7% type III structures. Predominant lobule type showed no association with cancer (p = 0.9). Postmenopausal women had a substantially higher proportion of type I lobules compared to premenopausal women, irrespective of the parity or cancer status (p < 0.001). Lobule type was not associated with menstrual phase classified by dates; however, when menstrual phase was classified using breast morphological characteristics, type I lobules were more abundant in follicular phase and type II in the luteal phase (p < 0.001). In conclusion, we did not observe a relationship between lobular architecture and breast cancer susceptibility when using smaller breast samples usually available in epidemiological studies, but these data highlight the need for menstrual phase stratification in future investigations.     

Adiposity Results in Metabolic and Inflammation Differences in Premenopausal and Postmenopausal Women Consistent with the Difference in Breast Cancer Risk

Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese. Expression levels of 21 target genes were determined using a TaqMan Low Density Array procedure. Breast tissue estradiol levels were measured by a liquid chromatography-tandem mass spectrometry procedure, and serum estradiol and follicle-stimulating hormone (FSH) were measured by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. We found that in postmenopausal women, serum and tissue estradiol levels were increased in those who were overweight, and serum FSH levels were decreased in obese status. Interestingly, RPS6KB1, an AMPK downstream-responsive gene for protein synthesis and cell growth, and estrogen receptor α (encoded by the ESR1 gene) and its target gene GATA3 were significantly decreased in rFNA of premenopausal, obese women. In postmenopausal women, RPS6KB1, ESR1, and GATA3 expression remained unchanged in relation to adiposity. However, prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin D1 (CCND1), and another ESR1 target gene, TFF1, were elevated in rFNA of obese postmenopausal women. Thus, as bodyweight increases, gene expression is indicative of increased proliferation in postmenopausal women but decreased proliferation in premenopausal women. Overall, our data reveal a novel process by which obesity promotes the risk of breast cancer in postmenopausal but not premenopausal women.     

The association of breast mitogens with mammographic densities

Radiologically dense breast tissue (mammographic density) is strongly associated with risk of breast cancer, but the biological basis for this association is unknown. In this study we have examined the association of circulating levels of hormones and growth factors with mammographic density. A total of 382 subjects, 193 premenopausal and 189 postmenopausal, without previous breast cancer or current hormone use, were selected in each of five categories of breast density from mammography units. Risk factor information, anthropometric measures, and blood samples were obtained, and oestradiol, progesterone, sex hormone binding globulin, growth hormone, insulin-like growth factor-I and its principal binding protein, and prolactin measured. Mammograms were digitised and measured using a computer-assisted method. After adjustment for other risk factors, we found in premenopausal women that serum insulin-like growth factor-I levels, and in postmenopausal women, serum levels of prolactin, were both significantly and positively associated with per cent density. Total oestradiol and progesterone levels were unrelated to per cent density in both groups. In postmenopausal women, free oestradiol (negatively), and sex hormone binding globulin (positively), were significantly related to per cent density. These data show an association between blood levels of breast mitogens and mammographic density, and suggest a biological basis for the associated risk of breast cancer.     

Birthweight and body size throughout life in relation to sex hormones and prolactin concentrations in premenopausal women.

The association of birthweight and body size throughout life with premenopausal breast cancer risk may be due, in part, to relationships with sex hormones. Therefore, we assessed whether birthweight, body shape at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, adult waist circumference and waist-to-hip ratio (WHR), and attained height were associated with the plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone-binding globulin (SHBG) in 592 premenopausal women, ages 33 to 52 years old, from the Nurses' Health Study II. About 85% of women provided blood samples during follicular and luteal menstrual phases; other women had a single untimed sample. We observed few associations between sex hormone levels and birthweight or body shape in childhood. However, adult BMI was inversely associated with SHBG (P trend < 0.001) and positively associated with free testosterone (P trend < 0.001) concentrations. Adult BMI was not associated with follicular or luteal free estradiol levels (P trend >or= 0.15) because it was inversely associated with total estradiol levels (P trend < 0.001 for follicular and luteal estradiol levels). Testosterone, androstenedione, and progesterone were inversely associated with BMI. Comparing women with a BMI of >or=30 versus <20 kg/m2, levels were higher by 53% for free testosterone and lower by 51% for SHBG, 39% for follicular estradiol, 20% for luteal estradiol, 14% for androstenedione, 13% for testosterone, and 20% for progesterone. We observed no clear associations between BMI at age 18, waist circumference, WHR, or height, and sex hormone concentrations. Our results suggest that effects on premenopausal sex hormone levels may be one mechanism through which adult adiposity, but not birthweight or childhood body size, affects premenopausal breast cancer risk.     

血清睾酮水平与乳腺癌雌、孕激素受体表达的相关性研究

目的:回顾性研究血清睾酮（testosterone,T）水平与乳腺癌雌激素受体（estrogen receptor,ER）,孕激素受体（progesterone receptor,PR）表达的相关性。方法:回顾性分析2016年1月至2018年12月在南京市妇幼保健院进行体检和治疗的63例健康女性,99例良性肿瘤,204例乳腺癌的临床病理资料,比较三组之间的血清睾酮水平的差异。将所有204例乳腺癌患者根据睾酮水平由低到高排序,按四分位数分为4组,采用Logistic回归比较不同睾酮水平下4组乳腺癌患者ER、PR、Her2表达状态的比值比（OR）。结果:乳腺癌组血清睾酮水平与乳腺良性肿瘤组、健康对照组相比差异均无统计学意义（P＞0.05）。ER+和PR+乳腺癌患者中血清睾酮水平分别高于ER-和PR-患者,而Her2+乳腺癌患者中血清睾酮水平低于Her2-患者,差异均有统计学意义（P＜0.05）。采用Logistic回归计算OR值,根据绝经与否进一步分层,其中T≥0.44 ng/mL组相对于T≤0.22 ng/mL组ER阳性表达的总体OR值为2.46（95%CI=1.04~5.86,P=0.042）,绝经前OR值为3.77（95%CI=1.11~12.80,P=0.034）,绝经后OR值为1.05（95%CI=0.28~3.92,P=0.945）;T≥0.44 ng/mL组相对于T≤0.22 ng/mL组PR阳性表达的总体OR值为3.69（95%CI=1.60~8.49,P=0.002）,绝经前OR值为4.80（95%CI=1.51~15.23,P=0.008）,绝经后OR值为1.78（95%CI=0.47~6.71,P=0.396）,结果显示绝经前乳腺癌患者中ER、PR的阳性表达与血清睾酮水平呈现出明显的正相关性;而Her2阳性表达与血清睾酮水平在总体、绝经前、绝经后乳腺癌患者中均未表现出明显的负相关性。结论:高血清睾酮水平与乳腺癌ER、PR的阳性表达呈正相关,在绝经前乳腺癌患者中表现尤为显著。血清睾酮水平可以作为预测绝经前激素受体状态的标志物之一。     

Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density

Insulin-like growth factors (IGFs) and insulin-like growth factor-binding proteins (IGFBPs) play a role in the normal development of breast tissue and possibly in the etiology of breast cancer. Breast density is one of the strongest predictors of breast cancer. In a cross-sectional analysis within the Nurses' Health Study, we compared the associations of plasma levels of endogenous IGF-I and IGFBP-3 with breast density in 65 premenopausal and 192 postmenopausal women. The digitized film screen mammograms were evaluated by the computer-assisted Toronto method, in which visually selected gray-scale cut points are used to assess breast density. Generalized linear models and Spearman's partial correlation coefficients described the associations between breast density and IGF-I, IGFBP-3, and the IGF-I:IGFBP-3 ratio. Premenopausal breast density was positively correlated with IGF-I and inversely correlated with IGFBP-3; the association was strongest for the IGF-I:IGFBP-3 ratio and breast density (r = 0.39; P = 0.004). In contrast, the correlation between breast density and the IGF-I:IGFBP-3 ratio among postmenopausal women was -0.02 (P = 0.83). The associations of IGF-I:IGFBP-3 ratio with breast density differed significantly between premenopausal and postmenopausal women (P = 0.01). Mammographic density is positively associated with plasma IGF-I levels and inversely associated with plasma IGFBP-3 levels among premenopausal women, but not among postmenopausal women. These results are consistent with previous studies that showed a positive association between a higher IGF-I:IGFBP-3 ratio and subsequent risk of breast cancer only among premenopausal women. The findings raise the possibility that premenopausal levels of IGF-I and IGFBP-3 could be in the etiological pathway that relates higher breast density with increased breast cancer risk.