Kathleen A. Calzone

Nurses transforming health care using genetics and genomics

Nurses are well positioned to incorporate genetic and genomic information across all aspects of the United States (U.S.) health care system. Nurses, the most trusted health professionals [1], make unique contributions to the field of human genetics and genomics and complement the work of other health care providers to improve the health of the public. Health care benefits greatly from the unprecedented and ongoing work elucidating the genetic/genomic basis of health, illness, disease risk, and treatment response. The progress in genetics and genomics is applicable to the entire spectrum of health care and all health professionals and as such to the entire nursing profession (2.9 million) [2] in the United States regardless of role, clinical specialty, or academic preparation. The majority of disease risk, health conditions and the therapies used to treat those conditions have a genetic and/or genomic element influenced by environmental, lifestyle, and other factors therefore impacting the entire nursing profession [3]. Nurses have intimate knowledge of the patient’s, family’s, and community’s perspectives; an understanding of biologic underpinnings; experience with genetic/genomic technologies and information; skills in communication and building coalitions; and most importantly, the public’s trust. Across the lifespan, nursing focuses on health promotion and disease prevention, which is an integral component of genetic/genomic health care practices. Awareness of nurses’ strengths and skills, together with the recognition that prevention is the hallmark of genetic/genomic health care, will inform public policymaking groups as they address issues that affect heath care practice in the area of genetics/genomics. Policy making process will be informed with new insights will be gained with inclusion of nurses and professional nursing organizations. These policies can facilitate the ability of U.S. health care systems to use genetic/genomic knowledge to promote health and manage disease.

Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression.

Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.

Genetic Testing for Cancer Susceptibility

Genetic testing for mutations in genes associated with an inherited predisposition to cancer is rapidly moving outside specialty genetic services and into mainstream health care. Surgeons, as front-line providers of cancer care, are uniquely positioned to identify those who may benefit from genetic testing and institute changes to their health care management based on those results. This article provides an overview of the critical elements of the process of genetic testing for cancer susceptibility.

A Blueprint for Genomic Nursing Science

PURPOSE This article reports on recommendations arising from an invitational workshop series held at the National Institutes of Health for the purposes of identifying critical genomics problems important to the health of the public that can be addressed through nursing science. The overall purpose of the Genomic Nursing State of the Science Initiative is to establish a nursing research blueprint based on gaps in the evidence and expert evaluation of the current state of the science and through public comment. ORGANIZING CONSTRUCTS A Genomic Nursing State of the Science Advisory Panel was convened in 2012 to develop the nursing research blueprint. The Advisory Panel, which met via two webinars and two in-person meetings, considered existing evidence from evidence reviews, testimony from key stakeholder groups, presentations from experts in research synthesis, and public comment. FINDINGS The genomic nursing science blueprint arising from the Genomic Nursing State of Science Advisory Panel focuses on biologic plausibility studies as well as interventions likely to improve a variety of outcomes (e.g., clinical, economic, environmental). It also includes all care settings and diverse populations. The focus is on (a) the client, defined as person, family, community, or population; (b) the context, targeting informatics support systems, capacity building, education, and environmental influences; and (c) cross-cutting themes. It was agreed that building capacity to measure the impact of nursing actions on costs, quality, and outcomes of patient care is a strategic and scientific priority if findings are to be synthesized and aggregated to inform practice and policy. CONCLUSIONS The genomic nursing science blueprint provides the framework for furthering genomic nursing science to improve health outcomes. This blueprint is an independent recommendation of the Advisory Panel with input from the public and is not a policy statement of the National Institutes of Health or the federal government. CLINICAL RELEVANCE This genomic nursing science blueprint targets research to build the evidence base to inform integration of genomics into nursing practice and regulation (such as nursing licensure requirements, institutional accreditation, and academic nursing school accreditation).

Genetics-Genomics Competencies and Nursing Regulation

PURPOSE The aim of this article is to explore the interaction between the integration of genetics-genomics competencies into nursing curricula and regulatory standards. By taking a global perspective of activity in this field, we aim to develop a framework that can inform strategic planning in relation to international genetics-genomics and nursing education. METHODS We focus our exploration around a small-scale international survey on the progress, achievements, and critical success factors of 10 countries in relation to the integration of genetics-genomics into nursing education, with exemplars from three of those countries. FINDINGS Analysis of the data generated 10 themes, each with several subthemes that play a critical role in the development of genetics-genomics in nursing education and practice. The themes were organized into three overarching themes: nursing in genetics, genetics in nursing, and recognition and support. Genetics-genomics competence is not fully integrated into nursing education at an appropriate level in any country, nor was it reflected robustly in current standards for registration and licensure. CONCLUSION Strong leadership from the specialist genetics community plays a critical role in defining genetics-genomics competence but the engagement of nursing professionals at senior levels in both government and regulatory institutions is essential if nurses are to be active participants in the innovations offered by genomic healthcare. CLINICAL RELEVANCE Safe and effective nursing practice must incorporate the needs of those with, at risk for, or susceptible to genetic-genomic conditions, as well as those who might benefit from the application of genomic technologies in the diagnosis and management of common conditions such as cancer and heart disease. The scope of such practice can be articulated though competence statements. Professional regulation defines the standard of competence that practicing nurses should demonstrate at initial registration and licensure.

Establishing the Outcome Indicators for the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics

The translation of genetics/genomics to clinical care has implications for nurses. The Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics, established by consensus, apply to all registered nurses. Learning outcomes and clinical practice indicators have been developed to provide additional guidance. The Essentials Advisory Group (EAG) established a team to establish the Outcome Indicators. A draft was developed based on published peer-reviewed documents and syllabi. The draft underwent three layers of review: (a) critique by the EAG; (b) review by representatives at a Genetics/Genomics Toolkit for Faculty meeting; and (c) review by workshop attendees of the American Association of Colleges of Nursings baccalaureate and masters education conferences, followed by EAGs final approval. Outcome Indicators clarify specific knowledge areas and suggest clinical performance indicators for each competency. They provide the foundation to establish a competency-based education repository with outcome indicator mapping matrixes for genetic/genomic education resources. A gap analysis of education resources identified resource deficits, and online unfolding case studies were developed. Outcome Indicators assist the academic and continuing education nurse community to prepare the nursing workforce in genetics/genomics and provide a platform from which to build tools needed to achieve this goal.

Introducing a New Competency Into Nursing Practice

As science advances, new competencies must be integrated into nursing practice to ensure the provision of safe, responsible, and accountable care. This article utilizes a model for integrating a new complex competency into nursing practice, using genomics as the exemplar competency. Nurses working at 23 Magnet® Recognition Program hospitals participated in a 1-year new competency integration effort.The aim of the study was to evaluate nursing workforce attitudes, receptivity, confidence, competency, knowledge, and practices regarding genomics. Results were analyzed using descriptive statistical techniques. Respondents were 7,798 licensed registered nurses. The majority (89%) said it was very or somewhat important for nurses to become more educated in the genetics of common diseases. Overall, the respondents felt genomics was important, but a genomic nursing competency deficit affecting all nurses regardless of academic preparation or role was observed. The study findings provide essential information to help guide the integration of a new competency into nursing practice.

Assessing breast cancer risk: genetic factors are not the whole story.

PREVIEW Genetic syndromes that convey a significant risk of breast cancer are responsible for a small but significant percentage of these cancers. However, the vast majority of breast cancers occur in women with no family history of the disease. Nongenetic risk factors include age, previous breast disease, breast tissue density, radiation exposure, and lifestyle factors, such as weight, exercise, and alcohol consumption. In this article, the authors outline genetic and other risk factors for breast cancer, explore risk-reduction strategies, and encourage primary care physicians to assess breast cancer risk in all their patients.

Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study

IntroductionMammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers.MethodsWe compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject’s digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject’s belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model’s discriminatory capacity.ResultsIn the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density.ConclusionsOur findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography.

THE ROLE OF THE NURSE IN CANCER GENETICS

Knowledge gained from the Human Genome Project and related genetic research is already impacting clinical oncology nursing practice. Because cancer is now understood to be a genetic disease, changes in the traditional approaches to prevention, diagnosis, and therapeutic management of cancer are becoming increasingly genetically based. Therefore, to ensure competency in oncology nursing practice at all levels, nurses must incorporate an understanding of the underlying biology of carcinogenesis and the molecular rationale underlying strategies to prevent, diagnose, and treat cancer.