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."

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.

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.

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.

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.

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.

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.

Preparation of human serum for prolactin measurement by multiple reaction monitoring mass spectrometry.

The measurement of the protein hormone prolactin (PRL) in biological samples has developed over the years into a routine clinical assay aiding the diagnosis of multiple medical conditions. PRL is known to exist in multiple isoforms circulating throughout the body. Current methodologies for measuring the PRL levels typically involve a variety of immunoassays. However, most of these tests are not capable of distinguishing between the different isoforms. To address this need, we have developed a highly specialized method employing multiple reaction monitoring mass spectrometry (MRM-MS) capable of monitoring seven distinct peptides from two of the most common prolactin isoforms (the 23 kDa PRL and its 16 kDa N-terminal cleavage product). Since serum is the main source of clinical specimen for the measurement of prolactin isoforms, the method described in this chapter is focused on the approach to processing whole serum samples for prolactin analysis via reversed-phase liquid chromatography (RPLC) and MRM-MS.

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.