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.

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.

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."

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.

Areas of strength and opportunities for growth in translational science education and training: Results of a scoping review from the NCATS Education Branch.

Translational science education and training (E&T) aims to prepare the translational workforce to accelerate progress along the translational pipeline toward solutions that improve human health. In 2020-2021, the National Center for Advancing Translational Sciences (NCATS) Education Branch conducted a scoping review of the E&T literature with this focus. The review used the methodological framework proposed by Arksey and O'Malley. PubMed, Education Resources Information Center (ERIC), and Embase were searched, and forward citations conducted. Screening of titles, abstracts, and full text identified 44 included articles. Data extraction facilitated analysis of E&T content, audiences, modalities, evaluations, and recommendations. The NCATS Translational Science Principles were used to identity described or recommended E&T content. Twenty-nine articles described a translational science E&T opportunity or its evaluation, and another 15 articles offered recommendations for translational science E&T. The most prevalent NCATS Translational Science Principles were boundary-crossing partnerships (77%) and cross-disciplinary team science (75%). Among publications describing E&T opportunities, the most reported modalities were experiential learning (64%) and courses (61%) and the most reported participants were graduate students (68%) and postdoctoral fellows (54%). About half of these articles (n = 15) reported an evaluation, covering a range of proximal to distal outcomes. Recommendations emphasized the value of translational science E&T across training and career stages and the use of varied modalities to reach diverse audiences. This review highlights strengths and opportunities for growth in translational science E&T. Enhancements to content, expansion of participants and modalities, and rigorous evaluations will contribute to building a highly qualified, diverse translational science workforce.

DEIA is essential to advance the goals of translational science: Perspectives from NCATS.

The National Center for Advancing Translational Science (NCATS) seeks to improve upon the translational process to advance research and treatment across all diseases and conditions and bring these interventions to all who need them. Addressing the racial/ethnic health disparities and health inequities that persist in screening, diagnosis, treatment, and health outcomes (e.g., morbidity, mortality) is central to NCATS' mission to deliver more interventions to all people more quickly. Working toward this goal will require enhancing diversity, equity, inclusion, and accessibility (DEIA) in the translational workforce and in research conducted across the translational continuum, to support health equity. This paper discusses how aspects of DEIA are integral to the mission of translational science (TS). It describes recent NIH and NCATS efforts to advance DEIA in the TS workforce and in the research we support. Additionally, NCATS is developing approaches to apply a lens of DEIA in its activities and research - with relevance to the activities of the TS community - and will elucidate these approaches through related examples of NCATS-led, partnered, and supported activities, working toward the Center's goal of bringing more treatments to all people more quickly.

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.

Evaluation of an online case study-based course in translational science for a broad scientific audience: Impacts on students' knowledge, attitudes, planned scientific activities, and career goals.

Purpose: There is a need for education activities in translational science (TS) that focus on teaching key principles, concepts, and approaches to effectively overcome common scientific and operational bottlenecks in the translational process. Delivering this content to the broad range of individuals interested in advancing translation will help to both expand and develop the TS workforce. Rigorous evaluations will build the evidence base for effective educational approaches for varied audiences. Methods: In 2020, the National Center for Advancing Translational Sciences offered an online case study-based course in TS for students across education and career stages. The course evaluation used baseline and endpoint student surveys to assess satisfaction with the course and impacts of participation on knowledge and attitudes relevant to TS and professional goals. Results: Of 112 students, 100 completed baseline and/or endpoint surveys, with 66 completing both. Most found the online format (n = 59, 83%) and case study approach (n = 62, 87%) moderately or very effective. There were statistically significant increases in TS knowledge (P < .001) and positive attitudes about team science in translational research (TR) (P < .001). Students reported the course increased their skills and knowledge in cross-disciplinary team science, the process of preclinical and clinical TR, and how their work fits into the translational spectrum, and increased their interest in scientific approaches used in the case study and careers in TS, TR, or team science. Conclusions: This online case study-based course effectively conveyed TS concepts to students from a range of backgrounds and enhanced their professional interests related to course content.

Advancing translational science education.

In this communication, the authors offer considerations for how the scientific community can capitalize on decades of translational science advances and experiential knowledge to develop new education opportunities for a diverse and highly skilled translational science workforce. Continued advancement of the field of translational science will require new education approaches that distill key concepts in translational science from past and ongoing research initiatives and teach this foundational knowledge to current and future translational scientists. These key concepts include generalizable scientific and operational principles to guide translational science, as well as evidence-informed practices. Inspired by this approach, the National Center for Advancing Translational Sciences (NCATS) has developed an initial set of guiding principles for translational science generated via case studies of multiple highly successful translational science initiatives, and is now teaching them via new education activities that aim to reach a broad scientific audience interested in translational science. Our goal with this review is to prompt continued conversation with the translational science community regarding capitalizing on our collective translational science knowledge to advance core content for translational science education and disseminating this content to a broad range of scientific audiences.

Teaching principles of translational science to a broad scientific audience using a case study approach: A pilot course from the National Center for Advancing Translational Sciences.

There are numerous examples of translational science innovations addressing challenges in the translational process, accelerating progress along the translational spectrum, and generating solutions relevant to a wide range of human health needs. Examining these successes through an education lens can identify core principles and effective practices that lead to successful translational outcomes. The National Center for Advancing Translational Sciences (NCATS) is identifying and teaching these core principles and practices to a broad audience via online courses in translational science which teach from case studies of NCATS-led or supported research initiatives. In this paper, we share our approach to the design of these courses and offer a detailed description of our initial course, which focused on a preclinical drug discovery and development project spanning academic and government settings. Course participants were from a variety of career stages and institutions. Participants rated the course high in overall value to them and in providing a unique window into the translational science process. We share our model for course development as well as initial findings from the course evaluation with the goal of continuing to stimulate development of novel education activities teaching foundational principles in translational science to a broad audience.

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.

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.

A systems approach to enable effective team science from the internal research program of the National Center for Advancing Translational Sciences.

The internal research program of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health aims to fundamentally transform the preclinical translational research process to get more treatments to more people more quickly. The program develops and implements innovative scientific and operational approaches that accelerate and enhance translation across many diverse projects. Cross-disciplinary team science is a defining feature of our organization, with scientists at all levels engaged in multiple research teams. Here, we share our systems approach to nurturing cross-disciplinary team science, which leverages organizational policies, structures, and processes. Policies including the organizational mission statement, principles for ethical conduct of research, performance review criteria, and training program objectives and approaches reinforce the value of team science to achieve the program's scientific goals. Structures including an organizational structure designed around solving translational problems, co-location of employees in a single state-of-the-art scientific facility, and shared-use laboratories, expertise and instrumentation facilitate collaboration. Processes including fluid team assembly, specialized project management, cross-agency partnerships, and decision making based on clear screening criteria and milestones enable effective team assembly and functioning. We share evidence of the impact of these approaches on the science and commercialization of findings and discuss pathways to broad adoption of similar approaches.

Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations.

The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy.

Plasma volume expansion in pregnancy: implications for biomarkers in population studies.

There is a growing body of literature focused on endogenous hormone exposures during pregnancy and subsequent cancer risk for both mother and offspring. Examples of these studies include those focused on the biological mechanism for the association of preeclampsia with reduced risk of breast cancer for mother and female offspring or studies that have examined hormone concentrations during pregnancy between different ethnic groups who vary in their rates of breast cancer incidence. Although these studies seem relatively straightforward in conception and analysis, measurement of the concentration of hormones and other biomarkers in pregnant subjects is influenced by plasma volume expansion (PVE). During pregnancy, the maternal plasma volume expands 45% on average to provide for the greater circulatory needs of the maternal organs. Consequently, serum protein and hormone concentrations are greatly altered when comparing the pregnant with nonpregnant state. Assessing PVE also is complicated by the vast individual variation in PVE, ranging from minimal to a 2-fold increase. We propose that PVE needs to be evaluated when comparing biomarker concentrations during pregnancy in two populations that may differ with respect to PVE. Small body size is associated with lower PVE compared with higher body size. Therefore, we hypothesize that variation in PVE will influence the interpretation of differences in biomarker concentrations across population groups with respect to the etiologic significance of the biomarker to the disease under study (e.g., breast cancer). It is possible that some observations may be due only to differences in dilution between the two groups. We present PVE as a topic for consideration in population-based studies, examples of the types of studies where PVE may be relevant, and our own analysis of one such study in the text below.

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.

Effects of raloxifene on circulating prolactin and estradiol levels in premenopausal women at high risk for developing breast cancer.

BACKGROUND: Prolactin is a peptide hormone necessary for normal breast development that may contribute to breast tumorigenesis. Estrogen is a significant positive regulator of prolactin synthesis; therefore, raloxifene, a selective estrogen receptor modulator under study as a breast cancer prevention agent, may modulate both estradiol and prolactin levels by inhibiting estradiol from binding to its receptor. METHODS: Premenopausal women at increased risk for invasive breast cancer participated in a pilot chemoprevention trial and were given 60 mg raloxifene daily for 24 months. Fasting serum samples collected at baseline and after 12 months on drug were used to measure circulating prolactin, estradiol, and sex hormone binding globulin (SHBG) levels. RESULTS: Of the 27 subjects who completed 12 months of raloxifene, 23 had paired prolactin samples, and 20 had paired estradiol and SHBG samples. Prolactin levels did not significantly change with raloxifene treatment, but SHBG levels increased (mean change = 7.3 nmol/L; P = 0.0001; 95% confidence interval, 3.9-10.7). Estradiol (mean change = 42 pg/mL; P = 0.048; 95% confidence interval, 1-84 pg/mL) levels were elevated when comparing 15 of the 20 women with paired estradiol measurements who also had both of these samples taken during the early follicular phase of the menstrual cycle. CONCLUSIONS: This report is the first to examine the long-term effects of raloxifene on prolactin, estradiol, and SHBG levels in premenopausal women who are also at increased risk for developing invasive breast cancer. Raloxifene had no significant effect on prolactin levels but did increase estradiol and SHBG measurements.