Mary E. Ropka

Uptake Rates for Breast Cancer Genetic Testing: A Systematic Review

Purpose: Individuals and families dealing with the possibility of hereditary cancer risk face numerous decisions, including whether to obtain genetic testing. The purpose of this article is to determine what is known about the rate at which people obtain cancer genetic testing. Methods: Using MEDLINE, CINAHL, and PSYCHINFO plus reviewing reference lists of relevant articles, we identified 40 studies in May 2002 that addressed breast cancer–related decisions, enrolled adult participants, were published in 1990 or more recently, were peer-reviewed primary clinical studies, addressed genetic testing either alone or in combination with genetic counseling, and reported rates at which participants showed interest in and/or underwent cancer genetic testing. Information regarding study design, participants, and genetic testing uptake rates was recorded. Each article was reviewed for methodologic quality using a flexible quality review system applicable to all study types. Results: Of the 40 studies, 25 provided information about hypothetical genetic testing decisions, 14 about real decisions, and 1 about both. Mean hypothetical uptake was 66% (range, 20-96%) and real uptake was 59% (range, 25-96%). Multivariate logistic regression analyses found that decision type (real/hypothetical), personal and family history of breast cancer, and variability in sampling strategy, recruitment setting, and criteria for real and hypothetical uptake were independently associated with uptake. Our systematic review identified additional explanations for uptake variability (investigator influences, small sample sizes, variability in target populations, lack of clearly described sampling strategies, sampling methods open to bias, and variability in reporting associated risk factors). Conclusion: In addition to clinical characteristics, research methodologic issues are likely to be major determinants of variability in published breast cancer genetic testing uptake rates. An understanding of these issues will clarify to clinicians why their clinical experience may not be congruent with published rates and help guide future research. (Cancer Epidemiol Biomarkers Prev 2006;15(5):840–55)

Patient Decisions About Breast Cancer Chemoprevention: A Systematic Review and Meta-Analysis

PURPOSE Women at high risk of breast cancer face the complex decision of whether to take tamoxifen or raloxifene for breast cancer chemoprevention. We investigated what is known about decisions of women regarding chemoprevention. METHODS Using MEDLINE, CINAHL, and PSYCINFO, plus reviewing reference lists of relevant articles, in December 2009 we identified 13 studies that addressed patient decisions about breast cancer chemoprevention, were published in 1995 or later, were peer-reviewed primary clinical studies, and reported rates at which participants showed interest in (hypothetical uptake) or accepted (real uptake) chemoprevention medications. RESULTS Nine studies provided information about hypothetical breast cancer chemoprevention decisions (mean uptake rate, 24.7%) and five provided information about real decisions (mean uptake rate, 14.8%). The range of rates was wide, and each of the hypothetical uptake studies assessed interest differently. A logistic regression model found significant correlation with uptake of decision type (hypothetical versus real, odds ratio [OR] = 1.65; 95% CI, 1.26 to 2.16), educational or decision support intervention (provided v not, OR = 0.21; 95% CI, 0.17 to 0.27), and cohort risk for breast cancer (high-risk v general population, OR = 0.65; 95% CI, 0.56 to 0.75). Perceived vulnerability to breast cancer was consistently correlated with increased uptake, and concern for adverse effects was correlated with reduced uptake. All studies used a correlational/descriptive design, and most studies used convenience sampling strategies. CONCLUSION Breast cancer chemoprevention uptake rates are low and variation is wide. Hypothetical uptake rates are higher than real uptake, and interventions markedly reduce uptake. Research is needed that uses reproducible sampling methods and examines decision support strategies that lead to quality decisions.

Establishing the effectiveness of patient decision aids: key constructs and measurement instruments

BackgroundEstablishing the effectiveness of patient decision aids (PtDA) requires evidence that PtDAs improve the quality of the decision-making process and the quality of the choice made, or decision quality. The aim of this paper is to review the theoretical and empirical evidence for PtDA effectiveness and discuss emerging practical and research issues in the measurement of effectiveness.MethodsThis updated overview incorporates: a) an examination of the instruments used to measure five key decision-making process constructs (i.e., recognize decision, feel informed about options and outcomes, feel clear about goals and preferences, discuss goals and preferences with health care provider, and be involved in decisions) and decision quality constructs (i.e., knowledge, realistic expectations, values-choice agreement) within the 86 trials in the Cochrane review; and b) a summary of the 2011 Cochrane Collaboration’s review of PtDAs for these key constructs. Data on the constructs and instruments used were extracted independently by two authors from the 86 trials and any disagreements were resolved by discussion, with adjudication by a third party where required.ResultsThe 86 studies provide considerable evidence that PtDAs improve the decision-making process and decision quality. A majority of the studies (76/86; 88%) measured at least one of the key decision-making process or decision quality constructs. Seventeen different measurement instruments were used to measure decision-making process constructs, but no single instrument covered all five constructs. The Decisional Conflict Scale was most commonly used (n = 47), followed by the Control Preference Scale (n = 9). Many studies reported one or more constructs of decision quality, including knowledge (n = 59), realistic expectation of risks and benefits (n = 21), and values-choice agreement (n = 13). There was considerable variability in how values-choice agreement was defined and determined. No study reported on all key decision-making process and decision quality constructs.ConclusionsEvidence of PtDA effectiveness in improving the quality of the decision-making process and decision quality is strong and growing. There is not, however, consensus or standardization of measurement for either the decision-making process or decision quality. Additional work is needed to develop and evaluate measurement instruments and further explore theoretical issues to advance future research on PtDA effectiveness.

Treatment of urogenital atrophy with low-dose estradiol: preliminary results.

ObjectiveTo determine the lowest dosage of vaginally administered estradiol (E2) that reverses signs and symptoms of urogenital atrophy but does not substantially increase plasma E2 levels. DesignSingle-blind, single-arm study to determine the effects of de-escalating doses of vaginal estrogen on symptoms of urogenital atrophy, vaginal pH, and vaginal and urethral cytology. A questionnaire was used to assess subjective vaginal and urethral symptoms. Objective measurements included vaginal and urethral cytology, pH, endometrial biopsy, and 24-h circulating plasma luteinizing hormone, follicle-stimulating hormone (FSH), E2, and estrone levels obtained in a Clinical Research Unit. Circulating E2 levels were assayed with an ultrasensitive yeast bioassay with a detection limit of 0.02 pg/mL. Measurements were obtained over a 24-h period after administration of vehicle alone, on day 1 after the initial vaginal E2 dosage, after 3 weeks of daily E2 administration, and after an additional 9 weeks of twice weekly administration. ResultsFrom the first seven subjects studied at a 10-&mgr;g dose of E2, 100% responded according to predefined criteria. Vaginal cytology showed statistical improvement at 3 and 12 weeks. Urethral cytology was statistically improved after 12 weeks. Vaginal pH decreased from postmenopausal to premenopausal levels at both 3 and 12 weeks. Eighty-two percent of symptoms were cured or improved. Endometrium remained atrophic. Circulating E2 levels remained within the postmenopausal range of 3–10 pg/mL. ConclusionA 10-&mgr;g dose of vaginal E2 effectively treated urogenital atrophy in seven women and did not cause endometrial hyperplasia or increase E2 levels.

Health Heritage© a web-based tool for the collection and assessment of family health history: initial user experience and analytic validity.

A detailed family health history is currently the most potentially useful tool for diagnosis and risk assessment in clinical genetics. We developed and evaluated the usability and analytic validity of a patient-driven web-based family health history collection and analysis tool. Health Heritage© guides users through the collection of their family health history by relative, generates a pedigree, completes risk assessment, stratification, and recommendations for 89 conditions. We compared the performance of Health Heritage to that of Usual Care using a nonrandomized cohort trial of 109 volunteers. We contrasted the completeness and sensitivity of family health history collection and risk assessments derived from Health Heritage and Usual Care to those obtained by genetic counselors and genetic assessment teams. Nearly half (42%) of the Health Heritage participants reported discovery of health risks; 63% found the information easy to understand and 56% indicated it would change their health behavior. Health Heritage consistently outperformed Usual Care in the completeness and accuracy of family health history collection, identifying 60% of the elevated risk conditions specified by the genetic team versus 24% identified by Usual Care. Health Heritage also had greater sensitivity than Usual Care when comparing the identification of risks. These results suggest a strong role for automated family health history collection and risk assessment and underscore the potential of these data to serve as the foundation for comprehensive, cost-effective personalized genomic medicine.

Measurement of psychological factors associated with genetic testing for hereditary breast, ovarian and colon cancers

Despite numerous individual studies of psychological factors (depression, anxiety, distress) related to genetic testing for inherited cancer syndromes (CGT), there has been no systematic review of the psychological factors are measured among individuals at increased risk for hereditary breast, ovarian, or colon cancer. Our review provides an analysis of psychological factors in studies of CGT and discusses the instruments most commonly used to measure them. We performed a literature search using three major OVID databases from 1993 to January 2003. In the 19 studies that met our inclusion criteria, the most commonly assessed psychological factors were distress, anxiety, and depression. These factors were most often measured by the impact of event scale (IES), the state-trait anxiety inventory (STAI), and the Centers for Epidemiologic Studies and Depression scale (CES-D), respectively. Our results show deficits in the existing body of literature on psychological factors associated with CGT including limited documentation of psychometrics and variability in instrumentation.

Quality of Life and Chemotherapy-induced Neutropenia

This report summarizes recent data on neutropenia-related quality of life (QOL), including measures and interventions. Neutropenia is a common adverse effect of cytotoxic chemotherapy. The clinical significance of QOL in patients with chemotherapy-induced neutropenia (CIN) remains largely unexplored, although recent studies have shown a correlation between severe CIN and impaired QOL. Neutropenia typically occurs at the same time as other adverse effects. Data indicate that other toxicities are worse in the presence of febrile neutropenia and that these concurrent events may have a greater effect on QOL. Precautions that are taken to minimize the incidence of infection in patients with neutropenia may also affect their QOL. Future research should focus on accurately defining and measuring QOL in patients with CIN as well as on assessing ways to manage CIN more effectively and thus improve QOL. A number of interventions may have a positive influence on QOL in patients with cancer and neutropenia. Hematopoietic growth factor support, for example, reduces the incidence and sequelae of neutropenia and may provide a QOL benefit. To assess the effect of such interventions, neutropenia-specific QOL instruments, such as the Functional Assessment of Cancer Therapy-Neutropenia (FACT-N), may be valuable tools.

The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes.

Blogging through cancer: young women's persistent problems shared online.

Background: Many young women have turned to illness blogs to describe their lived experience with cancer. Blogs represent an untapped source of knowledge for researchers and clinicians. Objective: The purpose of this qualitative, exploratory study was to describe the life disruptions caused by cancer among young women, as well as to understand the facilitators and barriers in accessing healthcare services during and after active treatment. Methods: Sixteen Internet illness blogs were analyzed among women, aged between 20 and 39 years, diagnosed with cancer. These blogs were analyzed based on phenomenological qualitative methods and thematic analysis. Results: There were 4 dimensions of persistent problems that were articulated in the narratives of the young women without any relief. They included pain and fatigue, insurance and financial barriers, concerns related to fertility, and symptoms of posttraumatic stress and anxiety. Conclusion: The young women’s narratives capture fear, uncertainty, anger, and the debilitating nature of these persistent issues. Many of the women expressed their lingering physical, psychosocial, and emotional problems. Implications for Practice: Online illness narratives are a naturalistic form of inquiry that allows nurses to understand the experience of the patient through their own words and accounts. This study provides a foundation for nursing-based interventions that transcend traditional clinic experiences.

Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states

PurposeIn quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states.MethodsLiterature overview.ResultsThe heritability estimates for anxiety and depression are 30–40%. Related traits as neuroticism and loneliness are also highly heritable. The hypothalamo–pituitary–adrenal axis is the ‘final common pathway’ for most depressive symptoms. The many findings of investigated genes are promising but not definitive. Heritability estimates of positive emotional states range between 40 and 50%. Life satisfaction and mental health share common genetic factors with optimism and self-esteem. The prefrontal cortex is a candidate brain area for positive emotional states. Biological and genetic research into positive emotional states is scarce.ConclusionGenetically informative studies may provide insights into a wide variety of complex questions that traditional QL studies cannot deliver. This insight in turn will help us to design more effective supportive programs that could moderate the outcomes of genetically based predispositions.