Dejana Braithwaite

Lay Understanding of Familial Risk of Common Chronic Diseases: A Systematic Review and Synthesis of Qualitative Research

PURPOSE Although the family history is increasingly used for genetic risk assessment of common chronic diseases in primary care, evidence suggests that lay understanding about inheritance may conflict with medical models. This study systematically reviewed and synthesized the qualitative literature exploring understanding about familial risk held by persons with a family history of cancer, coronary artery disease, and diabetes mellitus. METHODS Twenty-two qualitative articles were found after a comprehensive literature search and were critically appraised; 11 were included. A meta-ethnographic approach was used to translate the studies across each other, synthesize the translation, and express the synthesis. RESULTS A dynamic process emerged by which a personal sense of vulnerability included some features that mirror the medical factors used to assess risk, such as the number of affected relatives. Other features are more personal, such as experience of a relative’s disease, sudden or premature death, perceived patterns of illness relating to gender or age at death, and comparisons between a person and an affected relative. The developing vulnerability is interpreted using personal mental models, including models of disease causation, inheritance, and fatalism. A person’s sense of vulnerability affects how that person copes with, and attempts to control, any perceived familial risk. CONCLUSIONS Persons with a family history of a common chronic disease develop a personal sense of vulnerability that is informed by the salience of their family history and interpreted within their personal models of disease causation and inheritance. Features that give meaning to familial risk may be perceived differently by patients and professionals. This review identifies key areas for health professionals to explore with patients that may improve the effectiveness of communication about disease risk and management.

Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy

IMPORTANCE Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age. OBJECTIVE To compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use. DESIGN Prospective cohort. SETTING Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries. PARTICIPANTS Data were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC. MAIN OUTCOMES AND MEASURES We used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (>20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval. RESULTS Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of womens breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively). CONCLUSIONS AND RELEVANCE Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.

Hypertension is an independent predictor of survival disparity between African-American and white breast cancer patients

The objective of this study was to determine whether comorbidity, or pre‐existing conditions, can account for some of the disparity in survival between African‐American and white breast cancer patients. A historical cohort study was conducted of 416 African‐American and 838 white women diagnosed with breast cancer between 1973 and 1986, and followed through 1999 in the Kaiser Permanente Northern California Medical Care Program. Information on comorbidity, tumor characteristics and breast cancer treatment was obtained from medical records, and Surveillance, Epidemiology and End Results, Northern California Cancer Center Registry. Associations between comorbidity and survival were analyzed with multiple Cox proportional hazards regression. Over a mean follow‐up of 9 years, African Americans had higher overall crude mortality than whites: 165 (39.7%) versus 279 (33.3%), respectively. When age, race, tumor characteristics and breast cancer treatment were controlled, the presence of hypertension was associated with all cause survival [hazard ratio (HR) = 1.33, 95% confidence intervals (CI) 1.07–1.67] and it accounted for 30% of racial disparity in this outcome. Hypertension‐augmented Charlson Comorbidity Index was a significant predictor of survival from all causes (HR = 1.32, 95%CI 1.18–1.49), competing causes (HR = 1.52, 95%CI 1.32–1.76) and breast cancer specific causes (HR = 1.18, 95%CI 1.03–1.35). In conclusion, hypertension has prognostic significance in relation to survival disparity between African‐American and white breast cancer patients. If our findings are replicated in contemporary cohorts, it may be necessary to include hypertension in the Charlson Comorbidity Index and other comorbidity measures.

Long-term Prognostic Role of Functional Limitations Among Women With Breast Cancer

BACKGROUND The long-term prognostic role of functional limitations among women with breast cancer is poorly understood. METHODS We studied a cohort of 2202 women with breast cancer at two sites in the United States, who provided complete information on body functions involving endurance, strength, muscular range of motion, and small muscle dexterity following initial adjuvant treatment. Associations of baseline functional limitations with survival were evaluated in delayed entry Cox proportional hazards models, with adjustment for baseline sociodemographic factors, body mass index, smoking, physical activity, comorbidity, tumor characteristics, and treatment. Difference in covariates between women with and without limitations was assessed with Pearson χ(2) and Student t tests. All statistical tests were two-sided. RESULTS During the median follow-up of 9 years, 112 deaths were attributable to competing causes (5% of the cohort) and 157 were attributable to breast cancer causes (7% of the cohort). At least one functional limitation was present in 39% of study participants. Proportionately, more breast cancer patients with functional limitations after initial adjuvant treatment were older, less educated, and obese (P < .001). In multivariable models, functional limitations were associated with a statistically significantly increased risk of death from all causes (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03 to 1.92) and from competing causes (HR = 2.60, 95% CI = 1.69 to 3.98) but not from breast cancer (HR = 0.90, 95% CI = 0.64 to 1.26). The relationship between functional limitations and overall survival differed by tumor stage (among women with stage I and stage III breast cancer, HR = 2.02, 95% CI = 1.23 to 3.32 and HR = 0.74, 95% CI = 0.42 to 1.30, respectively). CONCLUSION In this prospective cohort study, functional limitations following initial breast cancer treatment were associated with an important reduction in all-cause and competing-cause survival, irrespective of clinical, lifestyle, and sociodemographic factors.

Rituximab in Relapsing and Progressive Forms of Multiple Sclerosis: A Systematic Review

Background Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS. Objectives To evaluate the efficacy and safety of rituximab for MS treatment. Data collection Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies. Main results Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events. Author’s conclusion Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.

Screening Outcomes in Older US Women Undergoing Multiple Mammograms in Community Practice: Does Interval, Age, or Comorbidity Score Affect Tumor Characteristics or False Positive Rates?

Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. Methods From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Results Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.

Intention to Participate in Predictive Genetic Testing for Hereditary Cancer: The Role of Attitude toward Uncertainty

This study aimed to identify factors predictive of intentions to participate in genetic testing for hereditary cancer. Measures of the psychosocial influences on intention were based on the theories of reasoned action (TRA) and planned behaviour (TPB) and a new measure of Attitude toward Uncertainty. The participants (the breast cancer sample, n = 124; the colon cancer sample, n = 168) were recruited via a general practitioners patient database and asked to complete postal questionnaires. The overall response rate was 57.4% (54.7% in the colon cancer sample, 61.4% in the breast cancer sample). In the colon cancer sample, 72% of respondents stated that they would choose to participate in genetic testing for colon cancer susceptibility. In the breast cancer sample, 77% of respondents stated that they would choose to participate in genetic testing for breast cancer susceptibility. The TRA components (attitudes and subjective norms) and Attitude toward Uncertainty emerged as the strongest predictors of intention. The Attitude toward Uncertainty appears to moderate intention in that participants with more negative attitudes toward uncertainty are more likely to undergo the test than those seeking more certainty.

Prognostic Impact of Comorbidity among Long-Term Breast Cancer Survivors: Results from the LACE Study

Background: Little is known about the long-term impact of comorbidity among women with breast cancer. Methods: We studied a prospective cohort of 2,272 women with breast cancer, who were recruited following initial breast cancer treatment. Associations of the Charlson comorbidity index (CCI) and hypertension with survival were evaluated in delayed entry Cox proportional hazards models. Results: During a median follow-up of nine years, higher CCI scores were independently associated with an increased risk of death from all causes [HR, 1.32; 95% confidence interval (CI), 1.13–1.54] and from nonbreast cancer causes (HR, 1.55; 95% CI, 1.19–2.02), but not from breast cancer (HR, 1.14; 95% CI, 0.93–1.41). Hypertension was independently associated with an increased risk of death from all causes (HR, 1.55; 95% CI, 1.20–1.99), from nonbreast cancer causes (HR, 1.67; 95% CI, 1.10–2.54), and from breast cancer (HR, 1.47; 95% CI, 1.03–2.09), but these associations were no longer significant after adjustment for antihypertensive medication. The relationship between the CCI and overall survival was the strongest among women with stage I disease (stage I, HR, 1.65; 95% CI, 1.26–2.16 vs. stage III, HR, 0.53; 95% CI, 0.23–1.25). Conclusion: The CCI was independently associated with lower overall and nonbreast cancer survival, but not with breast cancer–specific survival. Impact: Comorbidity may play an important role in breast cancer outcomes. Cancer Epidemiol Biomarkers Prev; 21(7); 1115–25. ©2012 AACR.

The relative importance of predictors of body mass index change, overweight and obesity in adolescent girls

OBJECTIVE To determine the relative importance of familial, dietary, behavioral, psychological and social risk factors for predicting body mass index (BMI) change, and onset of overweight and obesity among adolescent girls. METHODS Data from the NHLBI Growth and Health Study (n = 2 150), a longitudinal cohort of girls, were used to identify the most important predictors of change in BMI percentile between the ages of 9 and 19 years, and second, risk for becoming overweight and obese. Forty-one baseline predictors were assessed using a tree-based regression method (Random forest) to rank the relative importance of risk factors. RESULTS The five factors that best predicted change in BMI percentile (p < 0.05) were related to family socio-economic position (income and parent education) and drive to restrict eating and weight (body dissatisfaction, drive for thinness and unhappiness with physical appearance). The factors that were statistically significant (p < 0.05) predictors of both onset of overweight and obesity were income, ineffectiveness and race. CONCLUSIONS Family socio-economic position and emotion regulation appeared as the top predictors of both BMI change and onset of overweight and obesity. Our results build upon prior findings that policies to prevent the onset of obesity during adolescence be targeted towards girls from lower socio-economic position households. Our findings also suggest several novel psychological factors including ineffectiveness as predictors of obesity during adolescence. These predictive findings offer a direction for future inquiry into adolescent obesity etiology using causal methods.

Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk Education Intervention Tool (CREdIT)

The Cancer Risk Education Intervention Tool (CREdIT) is a computer-based (non-interactive) slide presentation designed to educate low-literacy, and ethnically and racially diverse public hospital patients at risk of Hereditary Breast and Ovarian Cancer (HBOC) about genetics. To qualitatively evaluate participants’ experience with and perceptions of a genetic education program as an adjunct to genetic counseling, we conducted direct observations of the intervention, semi-structured in person interviews with 11 women who viewed CREdIT, and post-counseling questionnaires with the two participating genetic counselors. Five themes emerged from the analysis of interviews: (1) genetic counseling and testing for breast/ovarian cancer was a new concept; (2) CREdIT’s story format was particularly appealing; (3) changes in participants’ perceived risk for breast cancer varied; (4) some misunderstandings about individual risk and heredity persisted after CREdIT and counseling; (5) the context for viewing CREdIT shaped responses to the presentation. Observations demonstrated ways to make the information provided in CREdIT and by genetic counselors more consistent. In a post-session counselor questionnaire, counselors’ rating of the patient’s preparedness before the session was significantly higher for patients who viewed CREdIT prior to their appointments than for other patients. This novel educational tool fills a gap in HBOC education by tailoring information to women of lower literacy and diverse ethnic/racial backgrounds. The tool was well received by interview participants and counselors alike. Further study is needed to examine the varied effects of CREdIT on risk perception. In addition, the implementation of CREdIT in diverse clinical settings and the cultural adaptation of CREdIT to specific populations reflect important areas for future work.