Social Constructions, Biological Implications: A Structural Examination of Racial Disparities in Breast Cancer Subtype.

The triple-negative subtype of breast cancer is etiologically and clinically distinct from the more common, less aggressive, and more treatable form of estrogen receptor-positive breast cancer. Numerous population-based studies have found that black women are 2 to 3 times more likely to develop triple-negative breast cancer than white women. Much of the existing research on racial disparities in breast cancer subtype has focused on identifying predisposing biological or genetic factors associated with African ancestry. However, this approach ignores growing multidisciplinary evidence suggesting that contemporary racial stratification shapes a wide range of environmental and social exposures that can subsequently impact cellular physiology and even gene expression patterns. Geronimus’ weathering hypothesis provides a unique conceptual framework through which to consider how psychosocial and environmental stressors may structure the disruption of biological mechanisms according to race. Building upon this framework, my dissertation (1) integrates important findings from stress biology, breast cancer subtype, and health disparity research in the form of a critical literature review, (2) develops an alternative conceptual model for the examination of racial disparities in breast cancer subtype, and (3) tests aspects of the model in two empirical analyses, using a combination of state-wide cancer registry data, block group-level Census and American Community Survey data, individual-level reports of stress and discrimination, and daily cortisol decline, a purported biological measure of chronic stress exposure. My findings suggest that there are significant associations between neighborhood characteristics (i.e., socioeconomic status and racial composition) and odds of more aggressive breast cancer subtypes, particularly within highly segregated metropolitan areas. However, these associations differ by race/ethnicity and across age groups. In a separate study population, the same neighborhood sociodemographic features are also associated with significant variation in daily cortisol decline. Taken together, this work demonstrates the potential for alternative biopsychosocial pathways linking race to the risk of triple-negative breast cancer, and suggests new avenues for research and public health action.PHDHealth Behavior And Health EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/109008/1/elinnen_1.pd

Associations between breast cancer subtype and neighborhood socioeconomic and racial composition among Black and White women

PURPOSE: Studies of Black-White differences in breast cancer subtype often emphasize potential ancestry-associated genetic or lifestyle risk factors without fully considering how the social or economic implications of race in the U.S. may influence risk. We assess whether neighborhood racial composition and/or socioeconomic status are associated with odds of triple-negative breast cancer (TNBC) diagnosis relative to the less-aggressive hormone receptor-positive/HER2-negative subtype (HR+ /HER-), and whether the observed relationships vary across women\u27s race and age groups. METHODS: We use multilevel generalized estimating equation models to evaluate odds of TNBC vs. HR+ /HER2- subtypes in a population-based cohort of 7291 Black and 74,208 White women diagnosed with breast cancer from 2006 to 2014. Final models include both neighborhood-level variables, adjusting for individual demographics and tumor characteristics. RESULTS: Relative to the HR+ /HER- subtype, we found modestly lower odds of TNBC subtype among White women with higher neighborhood median household income (statistically significant within the 45-64 age group, OR = 0.981 per $10,000 increase). Among Black women, both higher neighborhood income and higher percentages of Black neighborhood residents were associated with lower odds of TNBC relative to HR+ /HER2-. The largest reduction was observed among Black women diagnosed at age ≥ 65 (OR = 0.938 per$10,000 increase; OR = 0.942 per 10% increase in Black residents). CONCLUSION: The relationships between neighborhood composition, neighborhood socioeconomic status, and odds of TNBC differ by race and age. Racially patterned social factors warrant further exploration in breast cancer subtype disparities research

Associations between self-referral and health behavior responses to genetic risk information

Background: Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies. Methods: Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer’s disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure. Results: Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P < 0.01). They also dropped out of the study before genetic risk disclosure less frequently (26% versus 41%, P < 0.001). Cohorts did not differ in their likelihood of reporting a change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p < 0.001) and diets (21% vs 12%, p = 0.016) six weeks post-disclosure, whereas differences between ε4-positive and ε4-negative ARPs were not evident for mental activities (15% vs 21%, p = 0.413) or diets (8% versus 16%, P = 0.190). Similarly, ε4-positive participants were more likely than ε4-negative participants to report intentions to change long-term care insurance among SRPs (20% vs 5%, p < 0.001), but not ARPs (5% versus 9%, P = 0.365). Conclusions: Individuals who proactively seek AD genetic risk assessment are more likely to undergo testing and use results to inform behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings. Trial registration ClinicalTrials.gov NCT00089882 and NCT00462917 Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0124-0) contains supplementary material, which is available to authorized users

Joanne Knight Breast Health Cohort at Siteman Cancer Center

PURPOSE: The Joanne Knight Breast Health Cohort was established to link breast cancer risk factors, mammographic breast density, benign breast biopsies and associated tissue markers, and blood markers in a diverse population of women undergoing routine mammographic screening to study risk factors and validate models for breast cancer risk prediction. METHODS: Women were recruited from November 2008 to April 2012 through the mammography service at the Joanne Knight Breast Health Center at Washington University in St. Louis, Missouri. Baseline questionnaire risk factors, blood, and screening mammograms were collected from 12,153 women. Of these, 1,672 were excluded for prior history of any cancer (except non-melanoma skin) or diagnosis of breast cancer within 6 months of blood draw/registration for the study, for a total of 10,481 women. Follow-up is through linking to electronic health records, tumor registry, and death register. Routine screening mammograms are collected every 1-2 years and incident benign breast biopsies and cancers are identified through record linkage to pathology and tumor registries. Formal fixed tissue samples are retrieved and stored for analysis. County-level measures of structural inequality were derived from publicly available resources. RESULTS: Cohort Composition: median age at entry was 54.8 years and 26.7% are African American. Through 2020, 74% of participants have had a medical center visit within the past year and 80% within the past 2 years representing an average of 9.7 person-years of follow-up from date of blood draw per participant. 9,997 women are continuing in follow-up. Data collected at baseline include breast cancer risk factors, plasma and white blood cells, and mammograms prior to baseline, at baseline, and during follow-up. CONCLUSION: This cohort assembled and followed in a routine mammography screening and care setting that serves a diverse population of women in the St. Louis region now provides opportunities to integrate study of questionnaire measures, plasma and DNA markers, benign and malignant tissue markers, and repeated breast image features into prospective evaluation for breast cancer etiology and outcomes

The impact of multiplex genetic testing on disease risk perceptions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110591/1/cge12403.pd

Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86823/1/j.1399-0004.2011.01739.x.pd

How do women at increased, but unexplained, familial risk of breast cancer perceive and manage their risk? A qualitative interview study

<p>Abstract</p> <p>Background</p> <p>The perception of breast cancer risk held by women who have not had breast cancer, and who are at increased, but unexplained, familial risk of breast cancer is poorly described. This study aims to describe risk perception and how it is related to screening behaviour for these women.</p> <p>Methods</p> <p>Participants were recruited from a population-based sample (the Australian Breast Cancer Family Study - ABCFS). The ABCFS includes women diagnosed with breast cancer and their relatives. For this study, women without breast cancer with at least one first- or second-degree relative diagnosed with breast cancer before age 50 were eligible unless a <it>BRCA1 </it>or <it>BRCA2 </it>mutation had been identified in their family. Data collection consisted of an audio recorded, semi-structured interview on the topic of breast cancer risk and screening decision-making. Data was analysed thematically.</p> <p>Results</p> <p>A total of 24 interviews were conducted, and saturation of the main themes was achieved. Women were classified into one of five groups: don't worry about cancer risk, but do screening; concerned about cancer risk, so do something; concerned about cancer risk, so why don't I do anything?; cancer inevitable; cancer unlikely.</p> <p>Conclusions</p> <p>The language and framework women use to describe their risk of breast cancer must be the starting point in attempts to enhance women's understanding of risk and their prevention behaviour.</p

A Randomized Controlled Trial of Disclosing Genetic Risk Information for Alzheimer’s Disease via Telephone

Purpose Telephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes. Methods: In a multisite trial of Alzheimer’s disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in-person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure. Results: Data from 257 participants showed that telephone disclosure occurred 7.4 days sooner and were 30% shorter, on average, than in-person disclosure (both p<0.001). Anxiety and depression scores were well below cutoffs for clinical concern across protocols. Comparing telephone and in-person disclosure protocols, 99% CIs of mean differences were within non-inferiority margins on scales assessing anxiety, depression, and test-related distress, but inconclusive about positive impact. No differences were observed on measures of recall and subjective impact. Sub-analyses supported non-inferiority on all outcomes among APOE ε4-negative participants. Sub-analyses were inconclusive for APOE ε4-positive participants, although mean anxiety and depression scores were still well below cutoffs for clinical concern. Conclusion: Telephone disclosure of APOE results and risk for Alzheimer’s disease is generally safe and helps providers meet demands for services, even when results identify an increased risk for disease