Blood concentrations of estradiol and sex hormone-binding globulin in relation to age at menarche in premenopausal British and Japanese women

In a cross-sectional study, serum estradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were not significantly related to age at menarche in premenopausal British women in the luteal or follicular phases of the cycle. In Japanese subjects in the luteal phase, a marginally higher concentration of E2 was observed in those who had undergone an early rather than a late menarche. In British women, previous oral contraceptive users had significantly lower luteal phase E2 concentrations than never users.     

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

Background:

Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.

Methods:

Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.

Results:

Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.

Conclusion:

Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.     

Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study

Background:

Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors.

Methods:

Within the Breakthrough Generations Study cohort, we conducted a case–control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus.

Results:

Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89–21.1) for oestradiol and 4.57 (95% CI: 1.75–11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50–69 years and 19.4% at ages 20–79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density.

Conclusions:

Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis.     

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women

The associations between endogenous sex hormone levels and breast cancer risk in postmenopausal women are well established. Mammographic density is a strong risk factor for breast cancer, and possibly an intermediate marker. However, the results from studies on the associations between endogenous sex hormones and mammographic density are conflicting. The authors examined the associations between circulating levels of sex hormones, sex hormone binding globulin (SHBG) and prolactin and mammographic densities among postmenopausal women not currently using postmenopausal hormone therapy (HT). The authors also examined if insulin-like growth factor-I (IGF-I) levels influenced the association between estrogen and mammographic density. Altogether, 722 postmenopausal participants in the Norwegian governmental mammographic screening program had endogenous hormone concentrations measured. Mammograms were classified according to percent and absolute mammographic density using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index and HT use, both plasma concentrations of SHBG (p-trend = 0.003) and estrone (p-trend = 0.07) were positively associated with percent mammographic density. When the analyses were stratified according to median IGF-I concentration, the weak association between estrone and mammographic density was strengthened among women with IGF-I levels below median, while the association disappeared among women with over median IGF-I levels (p for interaction = 0.02). In summary, the authors found a positive association between plasma SHBG levels and mammographic densities among 722 postmenopausal Norwegian women not currently using HT. Further, the authors found a positive but weak association between plasma estrone concentration and mammographic density, which appeared to be modified by IGF-I levels.     

Relationship between caffeine intake and plasma sex hormone concentrations in premenopausal and postmenopausal women

BACKGROUND:

Circulating estrogens and androgens are important factors in the development of various female cancers. Caffeine intake may decrease risk of breast and ovarian cancer, although the data are not entirely consistent. Whether or not caffeine affects cancer risk by altering sex hormone levels is currently unknown.

METHODS:

We examined the relationship of caffeine, coffee, decaffeinated coffee, and tea with plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone–binding globulin (SHBG) in 524 premenopausal and 713 postmenopausal women from the Nurses' Health Study (NHS) and NHSII.

RESULTS:

In premenopausal women, caffeine intake was inversely associated with luteal total and free estradiol, and positively associated with luteal progesterone levels (P‐trend = .02, .01, .03, respectively). Coffee intake was significantly associated with lower luteal total and free estradiol levels, but not luteal progesterone levels (P‐trend = .007, .004, .20, respectively). Among the postmenopausal women, there was a positive association between caffeine and coffee intake and SHBG levels (P‐trend = .03 and .06, respectively). No significant associations were detected with the other hormones.

CONCLUSIONS:

Data from this cross‐sectional study suggest that caffeine may alter circulating levels of luteal estrogens and SHBG, representing possible mechanisms by which coffee or caffeine may be associated with pre‐ and postmenopausal malignancies, respectively. Future studies evaluating how caffeine‐mediated alterations in sex hormones and binding protein levels affect the risk of female cancers are warranted. Cancer 2009. © 2009 American Cancer Society.     

Relationship between serum hormone concentrations,reproductive history,alcohol consumption and genetic polymorphisms in pre-menopausal women

Reproductive characteristics, alcohol intake and polymorphisms in genes encoding sex-steroid metabolizing enzymes might influence the risk of hormone-related cancers by changing circulating concentrations of sex hormones. The relationship between these factors and serum concentrations of estradiol, progesterone, androstenedione, testosterone and DHEA was evaluated in a cross-sectional study of 218 pre-menopausal women from Kaiser Permanente Health Plan in Portland, Oregon. Risk factor information was obtained from questionnaires and hormone serum concentrations were determined by radioimmunoassays. Genotypes for CYP11A 5'UTR(tttta)n, CYP17 5'-UTR -34 T>C, CYP19 IVS4(ttta)n, CYP1B1 (L432V and S453N) and COMT (V158M) were determined from genomic DNA samples. Increasing number of full-term pregnancies was associated with a significant decrease in late-follicular progesterone levels (p-trend = 0.03). Increasing alcohol consumption was associated with higher estradiol levels averaged through the menstrual cycle (p-trend = 0.009) and higher progesterone levels during luteal phase (p-trend = 0.04). Androstenedione and testosterone levels were higher among light to moderate drinkers compared to non-drinkers, although we only observe a significant trend with increasing levels of alcohol consumption for androstenedione. Women heterozygous or homozygous for the CYP1B1 L432V or the S453N polymorphisms had increased luteal estradiol levels (p-value = 0.04 for L432V and 0.04 for S453N). None of the other factors evaluated was significantly associated with serum concentration of hormones. In conclusion, results from this cross-sectional study of pre-menopausal women provide support for an association between light to moderate alcohol intake and elevated levels of estrogen and androgen levels. Our data suggest that circulating levels of progesterone might be related to parity and alcohol consumption, however the biological plausibility of the observed associations is unclear. We found little support for an influence of the evaluated genetic polymorphisms in the steroid synthesis and metabolism pathway on serum hormone levels, except for a possible effect of the CYP1B1 L432V and S453N polymorphisms on serum estradiol levels.     

Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States)

Objectives: Endogenous sex hormones are thought to be involved in breast and endometrial cancers, but few studies have evaluated the relationships between hormones and risk factors for these diseases. Methods: We related serum hormone and sex-hormone binding globulin (SHBG) levels to reproductive and lifestyle risk factors in a cross-sectional study of 125 postmenopausal women in five geographic regions of the United States. Results: The estrogens were associated positively, while SHBG was associated negatively with body mass index (wt/ht 2). Estrone, (E1), estrone sulfate, and bioavailable estradiol (BioE2) were inversely associated with height. Androstenedione was positively associated with age at menopause, while androstenedione, E1, estradiol, and BioE2 were inversely associated with age at menarche. Weekly alcohol drinkers had higher hormone levels, and lower SHBG levels than those who abstained. Androstenedione and E1 decreased with increasing levels of nonrecreational activity. Conclusions: Several of these findings support the hypothesis that breast and endometrial cancer risk factors are mediated, in part, through increased endogenous hormone levels. The androstenedione findings are of interest in light of studies relating androstenedione to endometrial and possibly breast cancer. An association of age at menarche with E2, independent of androstenedione, may reflect increased aromatase activity in women with earlier menarche.     

Hormone receptors and obesity in Japanese women with breast cancer

Summary An association between hormone receptors in primary breast cancer and obesity determined prior to mastectomy was investigated in 128 Japanese women. The following criteria for obesity were used: (1) weight 60 kg (132 lbs), (2) weight kg/height cm–105 1.3, (3) weight lbs/height in 2.30, (4) body surface area 1.56 m². In view of the 4 criteria, tumor estrogen receptor (ER) values 4 fmol/mg were observed in obese patients more often than in nonobese patients, though the difference was not statistically significant. The same tendency was observed in the postmenopausal subgroup, 62 patients, especially in the 36 patients more than 5 years beyond menopause. However, there was still no statistical difference between obese and nonobese patients because the number of subjects was small. The same tendency was observed in the case of progesterone receptor (PgR) (6 fmol/mg) as observed in the case of ER. Address for reprints: Dr. Keijiro Kuno, Department of Surgery, Cancer Institute Hospital, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo, Japan 170     

Incidence of breast cancer among postmenopausal, hypertensive women

Elevated blood pressure has been proposed to be a risk factor for breast cancer but the results remain controversial. In this study, the incidence of breast cancer among 9,112 postmenopausal, hypertensive women included in the community-based hypertension register of the North Karelia project was assessed through the Finnish Cancer Registry. The mean follow-up time was 27 years. The incidence of breast cancer in hypertensive women in our cohort was similar to the age and period specific population-based rates for Eastern Finland [the standardised incidence ratio 0.96 (95% confidence interval 0.86-1.05)]. In the Cox regression analysis, there was no association between blood pressure levels, or use of antihypertensive (AH) drugs, and breast cancer incidence, when all women were considered. There was a statistically significant interaction of the use of AH drugs at baseline and the diastolic blood pressure (DBP). Among women who were not using AH drugs at baseline, the DBP level was positively associated with the subsequent risk of breast cancer (hazard ratio 1.26/10 mm Hg, 95% confidence interval 1.06-1.46). In women with AH drugs at baseline, the DBP had an opposite effect of borderline significance (hazard ratio 0.90/10 mm Hg, 95% confidence interval 0.78-1.01). In conclusion, breast cancer incidence among postmenopausal hypertensive patients in general does not differ from that of general population. Elevated DBP levels may be associated with an increased breast cancer risk among nonpharmacologically treated women.     

Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies

To assess whether risk of breast cancer in young women is associated with differences in luteal-phase hormone production and to attempt to explain differences in risk of breast cancer of young Shanghai Chinese and Los Angeles white women, two concurrent case-control studies of serum hormone concentrations were conducted. Both studies were carefully controlled for the possible confounding effects of age, weight, height, pregnancy history, and day of the menstrual cycle, by individually matching cases and controls on these factors. Case eligibility was limited to women with localized breast cancer. Sixteen of 39 Shanghai breast-cancer cases were sampled prior to the histologic diagnosis of their disease. The remaining 23 Shanghai cases and all 42 Los Angeles cases were diagnosed, and treated by surgery only, at least six months prior to hormonal evaluation. All subjects were sampled on day 22 of the menstrual cycle. Overall, cases had 13.5% higher serum estradiol concentrations (p=0.038) with a case-to-control excess of 16.6% in Shanghai subjects (p=0.089) and 10.8% in Los Angeles subjects (p=0.23). There were no appreciable differences in amounts of sex-hormone binding globulin between cases and controls. Cases had lower progesterone levels than controls, but the situation was reversed when the analysis was restricted to subjects with evidence of ovulation. Los Angeles controls had 20.6% greater estradiol concentrations than Shanghai controls (p=0.036); adjustment for body weight accounted for only 25.7% of this difference. This higher level of estradiol in Los Angeles women could be an important part of the explanation of the two-to-three-fold differences in breast cancer incidence rates of women under age 45 in Shanghai and Los Angeles.Drs Bernstein, Ross, Pike and Henderson and Ms Hanisch are in the Department of Preventive Medicine, University of Southern California School of Medicine, 1420 San Pablo Street, PMB A-202, Los Angeles, CA 90033. Drs Yuan and Gao are with the Shanghai Cancer Institute, 2200 Xie Tu Road, Shanghai, People's Republic of China. Drs Lobo and Stanczyk are in the Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Women's Hospital, 1240 North Mission Road, Los Angeles, CA 90033. Reprint requests should be addressed to Dr Bernstein. This work was supported by grants CA17054 and CA33512 from the National Institutes of Health.     

食蟹猴妊娠早期血清生殖激素的变化

目的:通过研究食蟹猴妊娠早期生殖激素的变化,为进行食蟹猴胚胎-胎仔发育毒性试验提供数据支持。方法:食蟹猴在怀孕第0天(gestation day 0,GD0)和怀孕第20天(GD20)采血分离血清检测孕酮水平。怀孕的雌猴于GD27～GD100每周采血1次,采用化学发光法检测血清中雌二醇、孕酮和催乳素的水平。结果:怀孕雌猴GD20的孕酮水平显著高于GD0。GD0～GD27孕酮水平缓慢上升,GD27达到高峰后下降,在GD48至最低,随后至GD100呈逐渐上升趋势。GD0～GD27雌二醇水平也缓慢上升,之后降低,在GD34达到最低水平,随后呈上升趋势,至GD100达到最高。催乳素水平从CD0开始缓慢上升,GD69达最高,后趋于平稳。结论:食蟹猴妊娠早期主要生殖激素随妊娠发展呈现动态变化,孕酮水平可作为早孕诊断的辅助参考。     

Different types of postmenopausal hormone therapy and mammographic density in Norwegian women

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer. The HTs used in Scandinavia is associated with higher risk estimates than those used in most other countries. Mammographic density is one of the strongest risk factors for breast cancer, and possibly an intermediate marker for breast cancer. We decided to examine the relationship between use of different types of HT and mammographic density in Norwegian women. Altogether, 1,007 postmenopausal participants in the governmental mammographic screening program were asked about current and previous HT use. Mammograms were classified according to percent and absolute mammographic density. Overall, current users of HT had on average 3.6% higher mean percent mammographic density when compared with never users (p < 0.001). After adjustment for age at screening, number of children and BMI in a multivariate model, women using the continuous estradiol (E(2)) plus norethisterone acetate (NETA) combination had a mean percent mammographic density significantly higher than never users (6.1% absolute difference). Those using the continuous E(2) plus NETA combination had an 4.8% (absolute difference) higher mean percent mammographic density after <5 years of use when compared with never users, while the corresponding number for >or=5 years of use was 7% (p-trend < 0.001). We found similar associations when absolute mammographic density was used as the outcome variable. In summary, our study shows a statistical significant positive dose-response association between current use of the continuous E(2) plus NETA combination and both measures of mammographic density.     

Effect of tamoxifen on serum cholesterol in Japanese women with breast cancer

Background To investigate whether tamoxifen therapy has a favorable effect on plasma lipids, serum cholesterol levels were measured in 228 Japanese women with breast cancer (116 premenopausal women and 112 postmenopausal women). Methods These women were treated with tamoxifen or tamoxifen+chemotherapy (tamoxifen-treated group) or were given no therapy or chemotherapy alone (control group). Results There was no difference between cholesterol levels before treatment and after a 2-year follow-up period in these groups, except for the postmenopausal tamoxifen-treated group. In this particular group, the mean levels of serum cholesterol after 1 and 2 years of follow-up (197 and 188 mg/dL, respectively) were 8% and 12% lower than those before treatment (215 mg/dL,P<0.0001). In addition, the mean level of serum cholesterol after a 2-year follow-up period was significantly higher in the postmenopausal tamoxifen-treated group than in the postmenopausal control group (218 and 188 mg/dL, respectively,P=0.0066). Conclusions In multiple regression models that included age, body mass index, and chemohormonal therapy, only tamoxifen treatment appeared to predict the change between cholesterol levels before treatment and after 2-year follow-up in postmenopausal women. These results suggest that tamoxifen has the potential benefit of reducing the serum cholesterol level, which may be closely related to cardiovascular risk, in Japanese postmenopausal women.     

绝经后乳腺癌雌、孕激素受体状态与血清性激素水平的关系

目的探讨绝经后乳腺癌雌激素受体(ER)、孕激素受体(PR)状态与患者血清性激素水平的关系及意义。方法使用全自动免疫分析仪化学发光分析法检测41例乳腺癌患者血清性激素六项(LH、FSH、PRL、E2、P、T)水平,免疫组化EnVision二步法检测乳腺癌ER、PR表达状态。结果绝经后乳腺癌PR阴性组与PR阳性组比较,患者血清LH、FSH水平显著增高(P值分别为0.005和0.031),PRL、E2、P、T水平在二组间差异无统计学意义;在ER阴性组与ER阳性组之间所测性激素水平差异无统计学意义。结论绝经后乳腺癌PR表达状态可能与垂体激素LH、FSH水平有关。     

Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom)

Objective: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer. Methods: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance. Results: SHBG decreased with increasing body mass index and increasing waist–hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women. Conclusions: Certain factors such as obesity and perhaps waist–hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.     

Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women

Due to its potential effects on ovarian hormone production, physical activity has been proposed as a modifiable risk factor for breast cancer. The authors analyzed data from the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort to examine the association between various measures of physical activity and postmenopausal breast cancer risk. Information on physical activity was obtained in 1992 via a self-administered questionnaire for 72,608 postmenopausal female participants who were cancer-free. During the five year prospective follow-up, 1520 incident breast cancer cases were identified among these women. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and to adjust for potential confounding factors including mammography. Women who were most physically active (>42.0 MET-h/week) at baseline had 29% lower incidence rates than active women with the least activity (>0–7.0 MET-h/week) (95% CI, 0.49–1.02). The difference in risk was largest for localized breast cancer, and for women who did not use hormone replacement therapy (HRT) at enrollment. Our findings are consistent with other studies that show lower risk of postmenopausal breast cancer associated with regular physical activity.     

Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans.

Endogenous oestradiol is strongly associated with breast cancer risk but its determinants are poorly understood. To test the hypothesis that vegetarians have lower plasma oestradiol and higher sex hormone-binding globulin (SHBG) than meat-eaters we assayed samples from 640 premenopausal women (153 meat-eaters, 382 vegetarians, 105 vegans) and 457 post-menopausal women (223 meat-eaters, 196 vegetarians, 38 vegans). Vegetarians and vegans had lower mean body mass indices (BMI) and lower plasma cholesterol concentrations than meat-eaters, but there were no statistically significant differences between meat-eaters, vegetarians and vegans in pre- or post-menopausal plasma concentrations of oestradiol or SHBG. Before adjusting for BMI there were small differences in the direction expected, with the vegetarians and vegans having higher SHBG and lower oestradiol (more noticeable amongst post-menopausal women) than the meat-eaters. These small differences were essentially eliminated by adjusting for BMI. Thus this study implies that the relatively low BMI of vegetarians and vegans does cause small changes in SHBG and in post-menopausal oestradiol, but that the composition of vegetarian diets may not have any additional effects on these hormones.     

Associations of adult-attained height and early life energy restriction with postmenopausal breast cancer risk according to estrogen and progesterone receptor status

Adult-attained height is a marker for underlying mechanisms, such as cell growth, that may also influence postmenopausal breast cancer (BC) risk, perhaps specifically hormone-sensitive BC subtypes. Early life energy restriction may inhibit these mechanisms, resulting in shorter height and a reduced postmenopausal BC risk. Women (62,573) from the Netherlands Cohort Study completed a self-administered questionnaire in 1986 when 55–69 years old, and were followed-up for 20.3 years (case–cohort: N_subcohort = 2,438; N_cases = 3,354). Cox multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated for BC risk overall and by estrogen and progesterone receptor subtypes in relation to height and early life energy restriction during the Hunger Winter, War Years, and Economic Depression. Although energy restriction can only influence longitudinal growth in women exposed before and/or during the growth spurt, it may also influence BC risk when occurring after the growth spurt, possibly through different growth processes. Therefore, Cox analyses were additionally conducted according to timing of energy restriction in relation to the growth spurt. Height was associated with an increased BC risk (HR_{per 5cm} = 1.07, 95%CI:1.01–1.13), particularly hormone receptor-positive BC. Energy restriction before and/or during the growth spurt was associated with a decreased hormone receptor-positive BC risk. Energy restriction during the Hunger Winter increased the estrogen receptor-negative BC risk regardless of the timing of energy restriction. In conclusion, height and energy restriction before and/or during the growth spurt were both associated with hormone receptor-positive BC risk, in the direction as expected, indicating critical exposure windows for hormonal growth-related mechanisms.     

Effects of prednisolone on sex hormone binding globulin during primary endocrine treatment of advanced breast cancer

Summary Serum sex hormone binding globulin (SHBG) was measured in 21 pre and 39 postmenopausal women with advanced breast cancer before treatment and 1, 3, 6, 9 and 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice daily, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day.Ovarian irradiation was associated with a 25% reduction in serum SHBG levels 3 to 6 months after treatment whilst patients on tamoxifen experienced a rise of about 80% in serum SHBG levels after 1 to 3 months. In postmenopausal women prednisolone markedly dampened the effect of tamoxifen, reducing a 80% rise to about 20%. There was no relationship between SHBG levels and response to treatment.     

The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L).

BACKGROUND: The purpose of this study was to evaluate changes in serum lipid parameters {cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein(a) [Lp(a)]}, in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer (NCIC CTG MA.17L). PATIENTS AND METHODS: MA.17L is a substudy of MA.17, a randomized, double-blind, placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen. Patients consenting to participate in this companion study had blood drawn and lipid parameters (total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a), triglycerides) evaluated at baseline, 6 months, 12 months and yearly thereafter until completion of protocol therapy. It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial. RESULTS: Three hundred and forty seven women were enrolled in the study. The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months (P=0.049), in LDL cholesterol at 12 months (P=0.033) and triglycerides at 24 months (P=0.036). All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups. No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups. CONCLUSIONS: The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen. Results from this study suggests that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or Lp(a) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy. These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following standard tamoxifen therapy.