Objective:
The objective of the study was to evaluate the current state of clinical assays for estradiol in the context of their applications.
Participants:
The participants were appointed by the ...Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion.
Evidence:
Data were gathered from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), and the clinical and laboratory experience of the participants.
Consensus Process:
The statement was an effort of the committee and was reviewed by each member. The Clinical Affairs Committee, the Council of The Endocrine Society, and JCEM reviewers reviewed the manuscript and made recommendations.
Conclusions:
The measurement of estradiol in biological fluids is important in human biology from cradle to grave. In addition to its centrality in sexual development, it has significant effects on skin, blood vessels, bone, muscle, coagulation, hepatic cells, adipose tissue, the kidney, the gastrointestinal tract, brain, lung, and pancreas. Alterations in its plasma concentration have been implicated in coronary artery disease, stroke, and breast cancer. Although modern immunoassays and liquid chromatography/tandem mass spectrometry-based methods for estradiol are reasonably well suited to the diagnosis and management of infertility (nonetheless, imprecision and method-to-method differences remain problematic), the very low concentrations that appear to be crucial in nonreproductive tissues are a separate and more difficult issue. Such levels of estradiol are too low to be routinely measured accurately or precisely, and further evolution of analytical methods and the way in which estradiol is standardized is needed.
To prospectively examine whether the association between tubal ligation, hysterectomy, unilateral oophorectomy, and ovarian cancer varied by patient, tumor, and surgical characteristics.
Two ...prospective cohort studies (Nurses' Health Study and Nurses' Health Study II).
Not applicable.
A cohort of 121,700 married US female nurses, aged 30-55 years at baseline and another cohort of 116,430 US female nurses aged 25-42 years at baseline.
We obtained data on gynecologic surgeries and ovarian cancer incidence through biennial questionnaires. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for known and suspected ovarian cancer risk factors.
Confirmed incident epithelial ovarian cancer.
Overall, tubal ligation was associated with a decreased risk of ovarian cancer (HR, 0.76; 95% CI 0.64-0.90). The inverse association was stronger for nonserous tumors (HR, 0.57; 95% CI 0.40-0.82) and among women younger than 35 years at surgery (HR, 0.67; 95% CI 0.49-0.90). Hysterectomy was associated with a decreased risk of ovarian cancer (HR, 0.80; 95% CI 0.66-0.97) and was somewhat stronger for nonserous tumors (HR, 0.70; 95% CI 0.49-1.02). Unilateral oophorectomy was associated with a 30% lower risk (HR, 0.70; 95% CI 0.53-0.91), which did not differ by histologic subtype.
Our study provides further support that tubal ligation reduces the risk of ovarian cancer, particularly for nonserous tumors and when conducted before the age of 35 years. The inverse association with hysterectomy, along with the stronger associations for nonserous tumors, supports shared biologic mechanisms for tubal ligation and hysterectomy.
Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations ...have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20–25% (versus bottom 20–25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2–4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.
In 2007, the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a "probable" carcinogen (group 2A), noting that human evidence was limited. Using ...data from 2 prospective cohort studies, the Nurses' Health Study (1988-2012; n = 78,516) and Nurses' Health Study II (1989-2013; n = 114,559), we examined associations between rotating night-shift work and breast cancer risk. In the 2 cohorts, there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up. In the Nurses' Health Study, women with 30 years or more of shift work did not have a higher risk of breast cancer (hazard ratio (HR) = 0.95, 95% confidence interval (95% CI): 0.77, 1.17; P for trend = 0.63) compared with those who never did shift work, although follow-up occurred primarily after retirement from shift work. Among participants in the Nurses' Health Study II, who were younger than participants in the other cohort, the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline, reflecting young-adult exposure (HR = 2.15, 95% CI: 1.23, 3.73; P for trend = 0.23), and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used updated exposure information (HR = 1.40, 95% CI: 1.00, 1.97; P for trend = 0.74). In conclusion, long-term rotating night-shift work was associated with a higher risk of breast cancer, particularly among women who performed shift work during young adulthood. Further studies should explore the role of shift work timing on breast cancer risk.
Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, ...frequency of drinking and "binge" drinking) and consumption at different times of adult life are not well understood.
To evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption.
Prospective observational study of 105,986 women enrolled in the Nurses' Health Study followed up from 1980 until 2008 with an early adult alcohol assessment and 8 updated alcohol assessments.
Relative risks of developing invasive breast cancer.
During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk.
Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk.
Background Rotating night shift work imposes circadian strain and is linked to the risk of several chronic diseases. Purpose To examine associations between rotating night shift work and all-cause; ...cardiovascular disease (CVD); and cancer mortality in a prospective cohort study of 74,862 registered U.S. nurses from the Nurses’ Health Study. Methods Lifetime rotating night shift work (defined as ≥3 nights/month) information was collected in 1988. During 22 years (1988–2010) of follow-up, 14,181 deaths were documented, including 3,062 CVD and 5,413 cancer deaths. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) and 95% CIs. Results All-cause and CVD mortality were significantly increased among women with ≥5 years of rotating night shift work, compared to women who never worked night shifts. Specifically, for women with 6–14 and ≥15 years of rotating night shift work, the HRs were 1.11 (95% CI=1.06, 1.17) and 1.11 (95% CI=1.05, 1.18) for all-cause mortality and 1.19 (95% CI=1.07, 1.33) and 1.23 (95% CI=1.09, 1.38) for CVD mortality. There was no significant association between rotating night shift work and all-cancer mortality (HR≥15years =1.08, 95% CI=0.98, 1.19) or mortality of any individual cancer, with the exception of lung cancer (HR≥15years =1.25, 95% CI=1.04, 1.51). Conclusions Women working rotating night shifts for ≥5 years have a modest increase in all-cause and CVD mortality; those working ≥15 years of rotating night shift work have a modest increase in lung cancer mortality. These results add to prior evidence of a potentially detrimental effect of rotating night shift work on health and longevity.
No prior study to our knowledge has examined the joint contribution of a polygenic risk score (PRS), mammographic density (MD), and postmenopausal endogenous hormone levels-all well-confirmed risk ...factors for invasive breast cancer-to existing breast cancer risk prediction models.
We conducted a nested case-control study within the prospective Nurses' Health Study and Nurses' Health Study II including 4,006 cases and 7,874 controls ages 34-70 years up to 1 June 2010. We added a breast cancer PRS using 67 single nucleotide polymorphisms, MD, and circulating testosterone, estrone sulfate, and prolactin levels to existing risk models. We calculated area under the curve (AUC), controlling for age and stratified by menopausal status, for the 5-year absolute risk of invasive breast cancer. We estimated the population distribution of 5-year predicted risks for models with and without biomarkers. For the Gail model, the AUC improved (p-values < 0.001) from 55.9 to 64.1 (8.2 units) in premenopausal women (Gail + PRS + MD), from 55.5 to 66.0 (10.5 units) in postmenopausal women not using hormone therapy (HT) (Gail + PRS + MD + all hormones), and from 58.0 to 64.9 (6.9 units) in postmenopausal women using HT (Gail + PRS + MD + prolactin). For the Rosner-Colditz model, the corresponding AUCs improved (p-values < 0.001) by 5.7, 6.2, and 6.5 units. For estrogen-receptor-positive tumors, among postmenopausal women not using HT, the AUCs improved (p-values < 0.001) by 14.3 units for the Gail model and 7.3 units for the Rosner-Colditz model. Additionally, the percentage of 50-year-old women predicted to be at more than twice 5-year average risk (≥2.27%) was 0.2% for the Gail model alone and 6.6% for the Gail + PRS + MD + all hormones model. Limitations of our study included the limited racial/ethnic diversity of our cohort, and that general population exposure distributions were unavailable for some risk factors.
In this study, the addition of PRS, MD, and endogenous hormones substantially improved existing breast cancer risk prediction models. Further studies will be needed to confirm these findings and to determine whether improved risk prediction models have practical value in identifying women at higher risk who would most benefit from chemoprevention, screening, and other risk-reducing strategies.
The Nurses' Health Study has grown from a simple questionnaire-based study initiated in 1976 to a rich resource of information collected over 29 years. Important details about lifestyle have been ...collected throughout the study and, as the study has progressed, blood samples and DNA from buccal cells have been collected and stored. Tumour samples have also been collected from participants who developed cancer. Through analyses that integrate information from these various sources we are advancing our understanding of the causes of cancer and the potential for prevention.
Animal and in vitro studies suggest that aspirin may inhibit breast cancer metastasis. We studied whether aspirin use among women with breast cancer decreased their risk of death from breast cancer.
...This was a prospective observational study based on responses from 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002 and were observed until death or June 2006, whichever came first. The main outcome was breast cancer mortality risk according to number of days per week of aspirin use (0, 1, 2 to 5, or 6 to 7 days) first assessed at least 12 months after diagnosis and updated.
There were 341 breast cancer deaths. Aspirin use was associated with a decreased risk of breast cancer death. The adjusted relative risks (RRs) for 1, 2 to 5, and 6 to 7 days of aspirin use per week compared with no use were 1.07 (95% CI, 0.70 to 1.63), 0.29 (95% CI, 0.16 to 0.52), and 0.36 (95% CI, 0.24 to 0.54), respectively (test for linear trend, P < .001). This association did not differ appreciably by stage, menopausal status, body mass index, or estrogen receptor status. Results were similar for distant recurrence. The adjusted RRs were 0.91 (95% CI, 0.62 to 1.33), 0.40 (95% CI, 0.24 to 0.65), and 0.57 (95% CI, 0.39 to 0.82; test for trend, P = .03) for 1, 2 to 5, and 6 to 7 days of aspirin use, respectively.
Among women living at least 1 year after a breast cancer diagnosis, aspirin use was associated with a decreased risk of distant recurrence and breast cancer death.
PDF
