A Proposed Framework and Lexicon for Cancer Prevention.

SUMMARY: Cancer prevention is central to efforts to control the burden of cancer. We propose a new terminology framework to help guide these efforts and promote a key equity principle: "equal care for equal risk."

Leadership Roles and Activities Among Alumni Receiving Postdoctoral Fellowship Training in Cancer Prevention.

This study was conducted in 2016-2017 to better understand formal and informal leadership roles and activities of alumni from postdoctoral research training programs in cancer prevention. Data were obtained from surveys of 254 employed scientists who completed cancer prevention postdoctoral training within the National Cancer Institute (NCI) Cancer Prevention Fellowship Program, or at US research institutions through NCI-sponsored National Research Service Award (NRSA) individual postdoctoral fellowship (F32) grants, from 1987 to 2011. Fifteen questions categorized under Organizational Leadership, Research Leadership, Professional Society/Conference Leadership, and Broader Scientific/Health Community Leadership domains were analyzed. About 75% of respondents had at least one organizational leadership role or activity during their careers, and 13-34% reported some type of research, professional society/conference, or broader scientific/health community leadership within the past 5 years. Characteristics independently associated with leadership from regression models were being in earlier postdoctoral cohorts (8 items, range for statistically significant ORs = 2.8 to 10.8) and employment sector (8 items, range for statistically significant ORs = 0.4 to 11.7). Scientists whose race/ethnicity was other than white were less likely to report organizational leadership or management responsibilities (OR = 0.4, 95% CI 0.2-0.9). Here, many alumni from NCI-supported cancer prevention postdoctoral programs were involved in leadership, with postdoctoral cohort and employment sector being the factors most often associated with leadership roles and activities. Currently, there is relatively little research on leadership roles of biomedical scientists in general, or in cancer prevention specifically. This study begins to address this gap and provide a basis for more extensive studies of leadership roles and training of scientists.

Career Satisfaction and Perceived Salary Competitiveness among Individuals Who Completed Postdoctoral Research Training in Cancer Prevention.

Studies examining career satisfaction of biomedical scientists are limited, especially in the context of prior postdoctoral training. Here we focused on career satisfaction defined as satisfaction with one's career trajectory and perceived salary competitiveness among a predominantly Ph.D.-trained population of scientists who completed cancer prevention-related postdoctoral training between 1987-2011. National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP) alumni (n = 114), and previous recipients of NCI-sponsored Ruth L. Kirschstein National Research Service Award (NRSA/F32) postdoctoral fellowships (n = 140) completed online surveys. Associations of career satisfaction and perception of salary competitiveness with demographic, training, and employment-related factors were examined using logistic regression. Overall, 61% reported high levels of satisfaction with their career trajectory to-date. Higher salary (odds ratio [OR] = 2.86, 95% confidence interval [95% CI]: 1.07-7.69) and having more leadership roles (OR = 2.26, 95% CI:1.04-4.90) were independently associated with higher career satisfaction. Persons with race/ethnicity other than white (OR = 0.40, 95% CI: 0.20-0.82) or age ≥ 50 (OR = 0.40, 95%CI: 0.17-0.94) had lower career satisfaction levels. There were no statistically significant differences in career satisfaction levels by gender, scientific discipline, or employment sector. 74% perceived their current salary as competitive, but persons with 5-9, or ≥10 years in their current position reported lower levels (OR = 0.31, 95% CI: 0.15-0.65; and OR = 0.37, 95% CI: 0.16-0.87, respectively), as did individuals in government positions (OR = 0.33, 95% CI: 0.11-0.98). These data add to the understanding of career satisfaction of those with advanced training in biomedical research by examining these measures in relation to prior postdoctoral research training and across multiple career sectors.

The hallmarks of premalignant conditions: a molecular basis for cancer prevention.

The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures.

Independent Association of Postdoctoral Training with Subsequent Careers in Cancer Prevention.

The purpose of this study was to examine the career paths of alumni from the National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP), a structured in-house postdoctoral training program of 3-4 years duration, and specifically what proportion of the alumni were currently performing cancer prevention-related activities. The analyses here included 119 CPFP alumni and 85 unsuccessful CPFP applicants, all of whom completed postdoctoral training between 1987-2011 and are currently employed. Postdoctoral training experiences and current career outcomes data were collected via online surveys. Differences between groups were assessed using chi-square and Fisher's exact test p-values and subsequent regression analyses adjusted for differences between the groups. Compared to 15.3% of unsuccessful CPFP applicants, 52.1% of CPFP alumni (odds ratio [OR] = 4.99, 95% confidence interval [95% CI): 1.91-13.0) were currently spending the majority of their time working in cancer prevention. Among those doing any cancer prevention-focused work, 54.3% of CPFP alumni spent the majority of their time performing cancer prevention research activities when compared to 25.5% of unsuccessful applicants (OR = 4.26, 95% CI: 1.38-13.2). In addition to the independent effect of the NCI CPFP, scientific discipline, and employment sector were also associated with currently working in cancer prevention and involvement in cancer prevention research-related activities. These results from a structured postdoctoral training program are relevant not only to the cancer prevention community but also to those interested in evaluating alignment of postdoctoral training programs with available and desired career paths more broadly.

Alumni perspectives on career preparation during a postdoctoral training program: a qualitative study.

Published evaluations of career preparation of alumni from long-standing postdoctoral fellowship programs in the biomedical sciences are limited and often focus on quantitative analysis of data from extant publicly available sources. Qualitative methods provide the opportunity to gather robust information about specific program elements from structured postdoctoral training programs and the influence of this training on subsequent career paths of alumni. In-depth interviews with a subset of the National Cancer Institute's Cancer Prevention Fellowship Program (CPFP) alumni (n=27), representing more than 25 years of the program's history and multiple career sectors, were conducted to assess alumni reflections on the training environment and career preparation during their time in the CPFP. NVivo software was used to analyze data and identify major themes. Four main themes emerged from these interviews, including: the value of structured training curriculum, mentorship, transdisciplinary environment, and professional identity. Even when reflecting on training that occurred one to two decades earlier, alumni were able to highlight specific components of a structured postdoctoral training program as influencing their research and career trajectories. These results may have relevance for those interested in assessing how postdoctoral training can influence fellows throughout their careers and understanding salient features of structured programs.

Maternal circulating angiogenic factors in twin and singleton pregnancies.

OBJECTIVE: The purpose of this study was to compare longitudinally sampled maternal angiogenic proteins between singleton and twin pregnancies. STUDY DESIGN: Placental growth factor (PlGF), soluble feline McDonough sarcoma (fms)-like tyrosine kinase (sFlt)-1, and soluble endoglin from healthy pregnant women were quantified at 10, 18, 26, and 35 weeks' gestation (n=91), and during the third trimester (31-39 weeks) and at delivery (33-41 weeks; n=41). Geometric means and 95% confidence intervals were calculated for gestational age-adjusted angiogenic protein concentrations and compared between matched twin and singleton pregnancies. RESULTS: Maternal sFlt-1 concentrations and the sFlt-1/PlGF ratio were higher in twins than singletons across pregnancy and at delivery, with the greatest differences at week 35 (sFlt-1: 36,916 vs 10,151 pg/mL; P<.0001; sFlt-1/PlGF: 168.4 vs 29.0; P<.0001). Maternal concentrations of soluble endoglin also were higher in the third trimester and delivery. Maternal PlGF concentrations were lower in twin than singleton pregnancies at week 35 only (219.2 vs 350.2 pg/mL; P<.0001). Placental weight appeared to be inversely correlated with maternal sFlt-1/PlGF ratio at the end of pregnancy in both twins and singletons. CONCLUSION: Higher maternal antiangiogenic proteins in twin than singleton pregnancies does not appear to be due to greater placental mass in the former, and may be one explanation for the increased risk of preeclampsia in women carrying multiple gestations. Determining whether women with a history of multiple gestations have an altered cardiovascular disease and breast cancer risk, like those with a history of preeclampsia, is warranted.

Prolactin receptor expression and breast cancer: relationships with tumor characteristics among pre- and post-menopausal women in a population-based case-control study from Poland.

Previous studies have found an association between elevated circulating prolactin levels and increased risk of breast cancer. Prolactin stimulates breast cancer cell proliferation, migration, and survival via binding to the cell-surface prolactin receptor. The association of prolactin receptor expression with breast tumorigenesis remains unclear as studies that have focused on this association have had limited sample size and/or information about tumor characteristics. Here, we examined the association of prolactin expression with tumor characteristics among 736 cases, from a large population-based case-control study of breast cancer conducted in Poland (2000-2003), with detailed risk factor and pathology data. Tumors were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis of prolactin receptor expression. Association of prolactin receptor expression across strata of tumor characteristics was evaluated using χ (2) analysis and logistic regression. Prolactin receptor expression did not vary by menopausal status; therefore, data from pre- and post-menopausal women were combined in the analyses. Approximately 83 % of breast cancers were categorized as strong prolactin receptor staining. Negative/low prolactin receptor expression was independently associated with poorly differentiated (p = 1.2 × 10(-08)) and larger tumors (p = 0.0005). These associations were independent of estrogen receptor expression. This is the largest study to date in which the association of prolactin receptor expression with tumor characteristics has been evaluated. These data provide new avenues from which to explore the associations of the prolactin/prolactin receptor signaling network with breast tumorigenesis.

Health disparities around the world: perspectives from the 2012 Principles and Practice of Cancer Prevention and Control course at the National Cancer Institute.

INTRODUCTION: The National Cancer Institute Principles and Practice of Cancer Prevention and Control course is a 4-week course encompassing a variety of cancer prevention and control topics that is open to attendees from medical, academic, government, and related institutions around the world. Themes related to the challenges health disparities present to cancer prevention efforts and potential solutions to these issues emerged from facilitated group discussions among the 2012 course participants. MATERIALS AND METHODS: Small-group discussion sessions with participants (n = 85 from 33 different countries) and facilitators (n = 9) were held once per week throughout the 4-week course. Facilitators prepared open-ended questions related to course topics. Participants provided responses reflecting their opinions of topics on the basis of experiences in their countries. A thematic analysis was conducted to explore themes emerging from the discussion groups. RESULTS: The varied influences of health disparities on cancer prevention efforts among > 30 countries represented prominent themes across discussion groups. Participants discussed the interplay of individual characteristics, including knowledge and culture, interpersonal relationships such as family structure and gender roles, community and organizational factors such as unequal access to health care and access to treatment, and national-level factors including policy and government structure. CONCLUSION: The ideas and solutions presented here are from a geographically and professionally diverse group of individuals. The collective discussion highlighted the pervasiveness of health disparities across all areas represented by course participants and suggested that disparities are the largest impediment to achieving cancer prevention goals.

Outcome evaluation of the National Cancer Institute career development awards program.

The National Cancer Institute (NCI) career development (K) awards program supports investigators to develop their cancer research programs and achieve independence. The NCI Center for Cancer Training conducted a K program evaluation by analyzing outcomes of awardees and individuals who applied to the program but were not funded. The evaluation covered seven NCI mechanisms (K01, K07, K08, K11, K22, K23, and K25) between 1980 and 2008. Descriptive statistics and regression modeling were performed on the full cohort (n = 2,893 individuals, 4,081 K applications) and a comparison cohort described herein. K awardees proportionately received more subsequent NIH grants and authored more publications, and time to first R01 grant was unaffected. Of those not pursuing research, K awardees were more likely to participate in activities signaling continued scientific engagement. The NCI K program had a positive impact, not only on participants' biomedical research careers but also on achieving outcomes significant to the scientific enterprise.

Postpartum remodeling, lactation, and breast cancer risk: summary of a National Cancer Institute-sponsored workshop.

The pregnancy-lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes.

Maternal and cord steroid sex hormones, angiogenic factors, and insulin-like growth factor axis in African-American preeclamptic and uncomplicated pregnancies.

BACKGROUND: A history of a preeclamptic pregnancy has been associated with subsequent increased risk of cardiovascular disease in the mother and decreased risk of breast cancer in both the mother and offspring. The concentrations of steroid sex hormones, angiogenic factors, and other proteins during pregnancy are important components of the in utero environment and may mediate the association of preeclampsia with later health outcomes. This study sought to compare an extensive profile of biological markers in both maternal and umbilical cord samples in preeclamptic and uncomplicated pregnancies of a predominantly African-American population. METHODS: Steroid sex hormones, angiogenic factors, and components of the insulin-like growth factor axis were measured in maternal and umbilical cord sera from 48 pregnancies complicated by preeclampsia and 43 uncomplicated pregnancies. Regression models estimated the associations of these markers with preeclampsia, after adjusting for maternal and gestational age. RESULTS: Concentrations of androgens (testosterone p = 0.06 and androstenedione p = 0.08) and the anti-angiogenic factors soluble fms-like kinase 1 (p = 0.004) and soluble endoglin (p = 0.004) were higher in the maternal circulation of women diagnosed with preeclampsia. These findings also were noted when the analyses were restricted to only African-American participants (77% of overall study population). Furthermore, among African-Americans, cord insulin-like growth factor-1 was lower in preeclamptic pregnancies than in controls. CONCLUSIONS: The associations of maternal androgens and anti-angiogenic factors with preeclampsia are consistent with prior reports from predominantly Caucasian populations. Alterations in these analytes as well as other maternal and fetal biomarkers in preeclampsia could mediate the associations of preeclampsia with later health consequences.

The future workforce in cancer prevention: advancing discovery, research, and technology.

As part of a 2-day conference on October 15 and 16, 2009, a nine-member task force composed of scientists, clinicians, educators, administrators, and students from across the USA was formed to discuss research, discovery, and technology obstacles to progress in cancer prevention and control, specifically those related to the cancer prevention workforce. This article summarizes the task force's findings on the current state of the cancer prevention workforce in this area and its needs for the future. The task force identified two types of barriers impeding the current cancer prevention workforce in research, discovery, and technology from reaching its fullest potential: (1) limited cross-disciplinary research opportunities with underutilization of some disciplines is hampering discovery and research in cancer prevention, and (2) new research avenues are not being investigated because technology development and implementation are lagging. Examples of impediments and desired outcomes are provided in each of these areas. Recommended solutions to these problems are based on the goals of enhancing the current cancer prevention workforce and accelerating the pace of discovery and clinical translation.

Associations of pregnancy characteristics with maternal and cord steroid hormones, angiogenic factors, and insulin-like growth factor axis.

BACKGROUND: The objective of this study was to comprehensively profile biological factors in pregnancy that have been postulated to be important components of the in utero environment and may also have relevance to later susceptibility to cancer and other chronic diseases. METHODS: Steroid sex hormones, IGFs, and angiogenic factors were measured in maternal and cord serum from term normotensive pregnancies. Spearman correlations and linear regression estimated relationships among the biological factors and clinical characteristics. RESULTS: The analytes were generally not correlated between maternal and fetal circulations. However, significant correlations were demonstrated among several analytes within maternal or cord samples. A few analytes were associated with clinical characteristics (e.g., maternal IGF-1 and IGFBP-3 were inversely correlated with offspring birth weight, while maternal leptin and cord testosterone were positively correlated with this characteristic). Maternal androgens were higher in African-Americans than whites, and maternal PlGF and soluble fms-like tyrosine kinase-1 (sFlt-1) were higher in male than female offspring. CONCLUSIONS: There were significant correlations among analytes, but the patterns differed depending on whether they were measured in the maternal or fetal circulation. The number and magnitude of correlations among analytes, however, should affect the design and interpretation of future studies.

Expanding cancer prevention education to national and international audiences: the National Cancer Institute's Principles and Practice of Cancer Prevention and Control annual summer course.

The Summer Curriculum in Cancer Prevention has been sponsored by the National Cancer Institute's Cancer Prevention Fellowship Program for over two decades. This curriculum includes a 4-week course entitled "Principles and Practice of Cancer Prevention and Control." The ultimate goal of this course is to present the most current cancer prevention research to a diverse workforce of researchers and practitioners eager to address the current challenges in this field. The course covers the current status of cancer prevention research and practice, ranging from epidemiology and clinical practice, and from basic to behavioral science research. It is comprised of lectures grouped into nine modules representing broad and specific topics relevant to cancer prevention. Course participants come from a broad cross-section of career stages, professions, and research interests, and are from across the USA and other countries. Over time and in response to feedback from participants, the course has developed to meet the needs and expectations of this diverse audience, and may serve as a model for those interested in cancer prevention education and training in other countries.

Maternal angiogenic profile in pregnancies that remain normotensive.

OBJECTIVE: We sought to determine if maternal characteristics are associated with angiogenic profile in the first and second trimester of normotensive pregnancies. STUDY DESIGN: Circulating levels of maternal placental like growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt1), and soluble endoglin (sEng) were measured in serum samples collected during the first (median 11.3 weeks) and second trimester (median 17.1 weeks) of 182 normotensive pregnancies. Diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were measured at the same visits when samples were collected to measure angiogenic factors. Linear regression analysis was used to examine associations of the angiogenic measures with maternal characteristics. The association between blood pressure measures and concentrations of angiogenic factors was evaluated using Spearman correlation and linear regression analysis. RESULTS: In adjusted analyses, nulliparous women had higher sFlt1 concentrations in both first (p=0.06) and second (p=0.001) trimester. Higher BMI was associated with greater sFlt1 concentrations in both the first (p=0.004) and second trimester (p=0.008), but significantly lower sEng concentrations in both trimesters (p=0.002 for first trimester and p=0.0009 for second). Nulliparity and higher BMI also were associated with higher sFlt1/PLGF anti-angiogenic ratios in both first (p=0.05 and p=0.007, respectively) and second trimesters (p=0.003 and p=0.02, respectively). First trimester sFlt1 levels were weakly correlated with first trimester SBP (r(s)=0.18, p=0.03) and MAP (r(s)=0.16, p=0.04). Second trimester sEng levels were inversely associated with second trimester MAP (r(s)=-0.17, p=0.05). Including blood pressure measures in the linear regression models did not change the reported associations of angiogenic factors with maternal characteristics. CONCLUSIONS: These results demonstrate that even early in normotensive pregnancies maternal characteristics are associated with variations in angiogenic profile across this population.

The Ninth Annual American Association of cancer research international conference on frontiers in cancer prevention research.

UNLABELLED: The Ninth Annual AACR Frontiers in Cancer PREVENTION Research conference was held in Philadelphia in November 7-10, 2010. Its thematic focus was " PREVENTION: From Basic Science to Public Health Benefit." Telomere plasticity, the microenvironment, inflammation, transformation to the metastatic phenotype, and pathways to obesity were highlighted as important elements of carcinogenesis amenable to intervention. The integration of information from novel technologies related to physical biology, molecular and genetic profiles, and imaging along with behavioral and clinical parameters have advanced risk stratification and early detection. Cancer prevention represents a powerful testing ground for the development of individually tailored intervention and for increasing the efficiency of drug discovery. Advances in clinical trials relate to more efficient design strategies, have shown first-in-human targeting capabilities, and have developed powerful strategies to overcome accrual barriers. Tailored intervention strategies now show high efficacy on large cohorts across several cancer types. These successes are expected to increase.

Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: results from a population-based case-control study in Poland.

INTRODUCTION: Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study. METHODS: We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 matched controls, aged 20-74, and living in Warsaw or Lódz, Poland. Serum prolactin levels were measured by immunoassay in a subset of 773 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for genotype associations with breast cancer risk were estimated using unconditional logistic regression, adjusted for age and study site. Geometric mean prolactin levels were estimated using linear regression models adjusted for age, study site, blood collection time, and menstrual cycle day (premenopausal women). RESULTS: Three SNPs were associated with breast cancer risk: in premenopausal women, PRLR rs249537 (T vs. C per-allele OR 1.39, 95% CI 1.07 - 1.80, P = 0.01); and in postmenopausal women, PRLR rs7718468 (C vs. T per-allele OR 1.16, 95% CI 1.03 - 1.30, P = 0.01) and PRLR rs13436213 (A vs. G per-allele OR 1.13 95% CI 1.01 - 1.26, P = 0.04). However, mean serum prolactin levels for these SNPs did not vary by genotype (P-trend > 0.05). Other SNPs were associated with serum prolactin levels: PRLR rs62355518 (P-trend = 0.01), PRLR rs10941235 (P-trend = 0.01), PRLR rs1610218 (P-trend = 0.01), PRLR rs34024951 (P-trend = 0.02), and PRLR rs9292575 (P-trend = 0.03) in premenopausal controls and PRL rs849872 (P-trend = 0.01) in postmenopausal controls. CONCLUSIONS: Our data provide limited support for an association between common variations in PRLR and breast cancer risk. Altered serum prolactin levels were not associated with breast cancer risk-associated variants, suggesting that common genetic variation is not a strong predictor of prolactin-associated breast cancer risk in this population.

Association of serum sex steroid hormone hemodilution and body mass index among healthy postmenopausal women.

PURPOSE: Hemodilution refers to reduced concentrations of analytes in the blood secondary to increased fluid volume. Given that obesity is associated with expanded vascular volume, hemodilution may result in a lower ratio of blood concentrations of analytes among heavier subjects. Assessing the relationship of hormone concentration to total mass varies by body mass index (BMI) is etiologically important because obesity is related to hormone metabolism and cancer risk. METHODS: We evaluated data for 194 postmenopausal controls in an endometrial cancer case-control study. Height, weight, and serum hormone concentrations were measured previously. We estimated serum hormone mass from concentration based on estimates of calculated plasma volume. We assessed the effect of BMI on relationships of sex steroid hormone concentration and mass using multivariate linear regression. RESULTS: Higher BMI was associated with increased estrone, estrone sulfate, estradiol, and albumin-bound estradiol concentrations and masses (p-trend ≤ 0.001). With increasing BMI, androstenedione concentration did not change significantly (p-trend = 0.548), but its mass increased (p-trend = 0.024). CONCLUSIONS: Relationships of sex steroid hormone concentration and mass were generally similar, except for androstenedione in which the relationship was only significant for mass. Future studies to assess both sex steroid hormone concentration and mass may have value in etiological research.

Comparison of liquid chromatography-tandem mass spectrometry, RIA, and ELISA methods for measurement of urinary estrogens.

Absolute and relative concentrations of estrogens and estrogen metabolites are important for clinical decisions as well as for epidemiologic, experimental, and clinical research on hormonal carcinogenesis. RIA and ELISA are routinely used for measuring estrogen metabolites in blood and urine due to efficiency and low cost. Here, we compare absolute and ranked concentrations of estrone, estradiol, and estriol measured by indirect RIA and of 2-hydroxyestrone and 16alpha-hydroxyestrone measured by ELISA to the concentrations obtained using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures 15 estrogen metabolites concurrently. We used overnight urine samples collected from control women (362 premenopausal and 168 postmenopausal) participating in a population-based case-control study of breast cancer among Asian American women ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute concentrations for the five estrogen metabolites ranged from 1.6 to 2.9 and 1.4 to 11.8 times higher in premenopausal and postmenopausal women, respectively (all P < 0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r (r(s)) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and moderately correlated (r(s) = 0.4-0.8) in postmenopausal women. Measurements of the 2-hydroxyestrone:16alpha-hydroxyestrone ratio, a putative biomarker of breast cancer risk, were moderately correlated in premenopausal women (r(s) = 0.6-0.7) but only weakly correlated in postmenopausal women (r(s) = 0.2). LC-MS/MS had higher intraclass correlation coefficients (> or =99.6%) and lower coefficients of variation (< or =9.4%) than ELISA (> or =97.2% and < or =14.2%) and RIA (> or =95.2% and < or =17.8%). Comparison with the LC-MS/MS method suggests that the widely used RIA and ELISA estrogen metabolite measures may be problematic, especially at low estrogen metabolite levels characteristic of postmenopausal women.