School of Public Health
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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Note: Prior to July 1, 2007, the School of Public Health was named the College of Health & Human Performance.
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Item RACIAL AND ETHNIC DISPARITIES OF BREAST CANCER RISK: THE ROLE OF INDIVIDUAL AND NEIGHBORHOOD-LEVEL CARDIOMETABOLIC FACTORS(2023) Ogbenna, Bethany Townsend; Dallal, Cher; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Observed racial and ethnic disparities in breast cancer are complex, in part, due to biological and behavioral factors at the individual and neighborhood level. Cardiometabolic factors such as the use of cholesterol-lowering drugs and engaging in healthy lifestyle behaviors may reduce breast cancer risk, however, the current understanding of these factors among diverse racial and ethnic populations remains limited. Moreover, at the neighborhood-level, the extent to which neighborhood socioeconomic status (nSES) influences inflammatory profiles among racially and ethnically diverse populations remains unclear. Using data from the Multiethnic Cohort Study (MEC), this dissertation investigates cholesterol-lowering drug use (Aim I) and a Healthy Lifestyle Index (HLI) (Aim II) in relation to postmenopausal breast cancer risk by race and ethnicity; and, assesses associations between nSES and inflammatory biomarkers among adults (Aim III). Methods: Prospective cohort analyses were conducted among postmenopausal women who completed the third MEC follow-up questionnaire in 2003 (Aim 1, n=41,394) or the baseline questionnaire in 1993-1996 (Aim 2, n=65,561) and were followed until 2017 for invasive breast cancer diagnoses (n=1,681 and 4,555 cases, respectively). Multivariable adjusted hazard ratios [HR] and 95% confidence intervals [95% CI] were estimated using Cox proportional hazards regression. For Aim III, multivariable linear regression assessed cross-sectional associations between nSES and inflammatory serum biomarkers (adiponectin, leptin and C-reactive protein) among adults residing in California (n=6,919) and Hawaii (n=6,899) (2000-2017). Results: Cholesterol-lowering drug use (Aim 1) and duration was not associated with breast cancer risk among all women with no statistically significant heterogeneity in associations by race and ethnicity (p-interaction >0.05). In Aim 2 analyses, women with a higher HLI score (Tertile (T)) had a reduced risk of breast cancer (HRT3 vs T1: 0.76; 95% CI: 0.69, 0.84; HRT2 vs T1: 0.88; 95% CI: 0.79, 0.97) compared to women in the lowest HLI tertile with a significant dose-response observed (p-trend <0.01). Similar patterns were observed across all racial and ethnic groups of women. In California and Hawaii, individuals living in low nSES neighborhoods had higher serum levels of CRP (p-trend <0.001; p-trend = 0.02, respectively) and leptin (p-trend <0.001) while adiponectin levels were lower (p-trend <0.01; p-trend = 0.03, respectively) compared to individuals living in neighborhoods with high nSES. Additional adjustment for body mass index attenuated these associations (p-trend >0.05) (Aim III). Public Health Impact: Findings from this dissertation further support engaging in healthy lifestyle behaviors as a preventative strategy for breast cancer reduction among multiethnic populations of postmenopausal women whereas cholesterol-lowering drug use was not associated with reductions in risk. In addition, residing in low nSES neighborhoods was associated with less favorable inflammatory biomarkers levels.Item Effects of Tamoxifen Therapy on Breast Carcinogenesis: Epidemiological Associations and Biomechanisms of Action(2022) Ghosh, Rajrupa; Dallal, Cher; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Tamoxifen, a key chemopreventive and adjuvant endocrine therapy (ET) for breast cancer, is suggested to alter breast cancer risk factors including circulating hormones (estrogen and insulin-like growth factors (IGFs)) and breast density. However, the biological underpinnings of tamoxifen’s effect on these factors remain unclear. This dissertation evaluated effects of tamoxifen on estrogen metabolites (EMs), explored associations between circulating IGFs (IGF-I and IGFBP-3) and volume average sound speed measures (VASS) of breast density, and synthesized evidence from real-world studies to meta-analyze adjuvant ET in relation to contralateral breast cancer (CBC) risk. Methods: Within the Ultrasound Study of Tamoxifen, serial serum samples collected prior to and 12 months after tamoxifen treatment were used to assess longitudinal changes (paired t-tests) in 15 circulating EMs among postmenopausal women (n=23) (Aim 1), and changes in IGFs and VASS (n=53) (Aim 2). Multivariable linear regression examined associations between metabolites of tamoxifen and estrogen among pre- (n=33) and postmenopausal women (n=27) (Aim 1) and concomitant changes in IGFs and VASS (n=53) (Aim 2), 12 months after treatment initiation. In Aim 3, a random effects meta-analysis of observational studies (n=17, 287,576 participants) estimated relative risks (RR) and 95% confidence intervals (CI) for associations between ET and CBC risk among primary breast cancer patients overall, by menopausal status and CBC estrogen receptor (ER)-subtype. Results: Circulating 2-OH and 16-OH pathway EMs, IGF-I, and IGF-I:IGFBP-3 decreased 12 months after tamoxifen initiation (p <0.05; Aims 1 and 2). No associations were observed between concomitant changes in IGFs and VASS among tamoxifen-treated patients (Aim 2). In meta-analyses (Aim 3), endocrine therapy was associated with reduced CBC risk (RR: 0.62, 95% CI: 0.53, 0.73), with a greater reduction observed among premenopausal (RR: 0.58, 95% CI: 0.43, 0.78) versus postmenopausal women (RR: 0.72, 95% CI: 0.60, 0.87). Endocrine therapy reduced the risk of ER-positive (RR: 0.55, 95% CI: 0.43, 0.70) but not ER-negative CBC. Conclusion: The tamoxifen mediated decline of circulating 2-OH, 16-OH and IGF-I provides etiologic insight into the biomechanisms of tamoxifen on breast carcinogenesis. Meta-analyses of observational studies further support a chemopreventive role of endocrine therapy on CBC risk, particularly, ER-positive CBC.