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  • 1. Gibbs, Jacob Improvements in 3D breast treatment plan quality and efficiency through computer automation of tangential breast radiotherapy treatment plans

    Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2023, Biomedical Sciences (Medical Physics: Radiation Oncology)

    Breast cancer is the most common type of cancer in women. More than 287,000 cases of aggressive breast cancer were estimated to have been diagnosed in 2022, leading to roughly 43,000 deaths. Breast radiotherapy has been shown through more than 50 years of clinical trials to be as effective as other treatments such as mastectomy. Clinical efficacy combined with frequent breast cancer diagnosis means that a significant amount of time will be spent by clinical staff planning breast radiotherapy treatments. If the process of treatment planning could be automated, then this same clinical staff would have more time to devout to other less routine cases. The aim of study is to design a script protocol to automate the process of beam segment design and machine output weighting, then to test this protocol against datasets of different geometries. A beam segment generation and monitor unit (MU) weighting protocol was developed and designed within the RayStation treatment planning system (TPS) python software IDE. The design of the protocol is to take human designed open fields and create sub-fields, or segments (FiF – or Field-in-Field), to increase the homogeneity of the radiation distribution. The protocol was tested on 10 CT datasets with five right side breast targets and five left side breast targets. Dose-volume statistics, dose distributions, and homogeneity index were calculated along with other plan parameters to test against recent published literature. The study found an average homogeneity index of 0.10 across all 10 plans, and no hot spot above 107% when normalized to 95% of prescription dose to 95% of the target volume (or D95=95%). This normalization to the prescription dose level is the gold standard in clinical trials, including the Fast, Fast-Forward, and RTOG-1005 trials. The study also noted higher than expected out-of-field dose to the contralateral breast. The homogeneity of the radiation distribution of the plan is the only factor which was sign (open full item for complete abstract)
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    Committee: Nicholas Sperling (Committee Chair); David Pearson (Committee Member); Sulaiman Aldoohan (Committee Member) Subjects: Oncology; Physics; Radiation; Therapy

  • 2. Wilkinson, Austin Investigating Prone Breast Treatment Plan Robustness and Attenuation of Prone Breast Board

    Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2020, Biomedical Sciences (Medical Physics: Radiation Oncology)

    Breast cancer patients are often treated in the prone position to improve dose homogeneity and cosmetic outcome. This is especially common when the patient's anatomy is more pendulous. A breast board is used to support the patient on the treatment table. This breast board creates a source of setup error as well as a source of error in the dose calculations of the treatment planning system. This study looks at two different methods for characterizing the board in the treatment planning system, compares the robustness of two different treatment planning methods across seven patients, and investigates the scatter contribution from the breast board. The first characterizing method was the material override method where a bulk density was assigned to the board shell and interior. The second characterizing method was the ROI type external method where the native CT numbers calculated during the simulation were used. A vertical transmission factor profile of the breast board was produced using each method and compared to the profiles obtained from an experimental setup. Seven previously anonymized patients were retrospectively selected, and two plans were made for each patient using the control point method and the augmented wedge method. The control point method is also known as “field-in-field”. This is when hot spots are covered with MLCs and the relative weights of the fields are changed to remove the hot spot. The augmented wedge method was when wedges and control points were used in the same plan. Planning with wedges alone was found to not be feasible. The plans had to have matching prescription coverage of 95%, as well as similar dose statistics. The robustness was compared by calculating the change in dose to a point in the dose shadow of the board when the board was completely removed, as well as the change in hotspot dose when the isocenter was slightly perturbed. The scatter contribution was investigated by measuring the skin dose of a virtual breast pha (open full item for complete abstract)
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    Committee: David Pearson (Committee Chair); E Parsai (Committee Member); Nicholas Sperling (Committee Member) Subjects: Physics; Radiation

  • 3. Masterson, Kaleb Mammography Concordance among Sexual Minority Individuals at Elevated Risk of Breast/Chest Cancer: Examining the Roles of Race and Healthcare System Distrust

    Master of Science, The Ohio State University, 2023, Public Health

    Background: In the United States, individuals assigned female at birth have about a 13% lifetime risk of breast/chest cancer. Those with a family history of breast/chest cancer or a BRCA gene mutation are at elevated risk of the disease, with greater than or equal to 20% lifetime risk. However, only a small proportion of individuals at high risk utilize available preventive services like mammography screening. Individuals of sexual minority identity and Black individuals experience increased levels of healthcare distrust. Healthcare distrust in turn is associated with lower rates of mammography screening utilization. Aim: Our study aim was to examine the relationship between healthcare distrust, sexual minority identity, and Black race to determine how they are related to mammography screening concordance rates among individuals at objectively elevated risk. We further sought to determine if healthcare distrust mediated the relationship between sexual minority identity and mammography discordance. Methods: We used survey data from The Daughter Sister Mother Project, a cross-sectional web survey conducted from 2018 to 2019 that used convenience sampling methods. Eligible participants were 18 to 75 years of age, identified as non-Hispanic White or non-Hispanic Black/African American, identified their sex as “female”, had a family history of breast/chest cancer or a BRCA gene mutation, and had no prior history of cancer. Our analysis focused on the high-risk subsample of participants, defined as individuals with a self-reported BRCA mutation or greater than 20% lifetime risk according to 1 or more risk prediction models. The primary exposure for this analysis was sexual minority identity and the primary outcome was mammography concordance, defined as reporting receipt of a mammogram within the last year if recommended according to National Comprehensive Cancer Network (NCCN) screening guidelines for women at high risk. Healthcare distrust was measured using the Rev (open full item for complete abstract)
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    Committee: Tasleem Padamsee (Committee Member); Alison Norris (Advisor) Subjects: Black Studies; Epidemiology; Glbt Studies; Health; Health Care; Health Care Management; Health Sciences; Public Health

  • 4. Clark, Cammi When Bad Genes Ruin a Perfectly Good Outlook: Psychological Implications of Hereditary Breast and Ovarian Cancer via Narrative Inquiry Methodology

    Ph.D., Antioch University, 2019, Leadership and Change

    Scientists debunked the belief that breast cancer is always viral with the mid-90s discovery of the first hereditary genetic mutation linked to a significantly higher-than average chance of breast and ovarian cancer. This genetic condition, called Hereditary Breast and Ovarian Cancer (HBOC), passes the mutation from generation to generation in a family. Thousands of variations of such mutations exist, and carriers account for 10 to 15% of all breast cancer, and up to 20% of ovarian (Childers et al., 2017). In addition, genetic testing uncovered a rapidly rising number of healthy people (never had breast/ovarian cancer) who are also carriers, flooding healthcare providers seeking potential options to reduce their elevated risk. Those prophylactic measures are invasive, permanent and can cause physical—and emotional—scarring. As a newer medical phenomenon, few, if any, studies address the potential psychological implications, which include fear, anxiety, guilt, family tension, and more. Using narrative inquiry methodology, this study analyzes the authentic lived or felt experiences of individuals when they learn that they have inherited a mutation that significantly increases their risk of breast, ovarian and related cancers, and their choices that directly affect their effort to outrun a cancer that may never come. This dissertation is accompanied by the author's MP4 video introduction and is available in open access at AURA: Antioch University Repository and Archive, http://aura.antioch.edu/ and Ohiolink ETD Center, https://etd.ohiolink.edu/
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    Committee: Elizabeth Holloway PhD (Committee Chair); Jon Wergin PhD (Committee Member); Piri Welcsh PhD (Committee Member) Subjects: Alternative Medicine; Behavioral Psychology; Communication; Educational Leadership; Families and Family Life; Genetics; Health; Health Care; Health Care Management; Health Education; Journalism; Psychology

  • 5. Coltri, Julia Transgender male patients and hereditary breast cancer risk: broaching difficult topics to reduce healthcare disparities

    Master of Science, The Ohio State University, 2019, Genetic Counseling

    Transgender individuals face significant healthcare disparities due to discrimination, which include reluctance to disclose, lack of provider experience and resources, structural barriers, and financial barriers. No consensus guidelines have been developed for breast cancer risk assessment and screening in transgender male patients. Breast health can be a difficult topic for transgender men, as it brings them into female centered spaces and can lead to experiences of gender dysphoria. This research aims to elucidate barriers to breast cancer screening and genetic risk evaluation for transmasculine individuals. Research questions aimed to determine what the level of awareness transgender men have about breast cancer risk and screening, and the factors that lead to positive or distressing conversations about breast health with these patients. We aim to determine how healthcare providers can foster a safe and affirming environment that increases comfort and reduces perceptions of discrimination and gender related dysphoria with a focus on genetic counseling for hereditary breast cancer risk assessment. Recommendations are made for improving the clinical experiences of these individuals including using mirroring an individual's terminology for their anatomy, providing gender affirming patient resources, addressing the gendered cultural discussion around breast cancer, using correct name and pronouns, and acknowledging the topic as potentially difficult.
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    Committee: Robert Pilarski MS, MSW, LGC (Advisor); Leigha Senter MS, LGC (Committee Member); Kandamurugu Manickam MD (Committee Member); Melissa Davis MD (Other) Subjects: Gender; Gender Studies; Genetics; Glbt Studies; Health; Health Care; Medicine

  • 6. Zalles, Nicole Effects of MicroRNA modulation of PLK1 in Breast Cancer in combination with PLK1 inhibitor NMS-P937

    Doctor of Philosophy, The Ohio State University, 2019, Biomedical Sciences

    The elucidation of more universal therapeutic targets is key to effectively combat the heterogeneity of breast cancer (BrCa). MicroRNAs (miRNAs) are small noncoding RNAs that are an abundant class of endogenous regulatory molecules, which act by targeting mRNAs for cleavage and/or translational repression. Continuing studies into BrCa genetics show that the various subtypes of BrCa are also affected by miRNA activity, which can even influence drug response. This prompted our investigation into the nuances of how miRNAs may influence BrCa behavior and response to treatment with targeted therapies, focusing on the proto-oncogene Polo-like Kinase 1 (PLK1). PLK1 plays an important role in the cell cycle, and is considered to be a proto-oncogene. Inhibiting PLK1 in has shown promise in reducing tumor volume and promoting tumor cell death in various cancers. A member of the miRNA-183 cluster, miRNA-183-5p, was found to bind to the 3' UTR of PLK1, with transiently-induced overexpression resulting in reduced expression levels of the active PLK1 protein. We also discovered that the miRNA-regulated reduction of PLK1 influenced the expression of other proteins in the PLK1 pathway, and affected cancer cell response to a PLK1-specific inhibitor, NMS-P937. The activity of miRNA-183-5p on PLK1 demonstrated an effect on cancer cell apoptosis following treatment with NMS-P937, suggesting a link with miRNA-183-5p expression and the efficacy of PLK1-specific inhibition in breast cancer cell lines. MiRNA-mediated regulation plays an important role in the initiation, progression and drug response of tumors. Understanding how miRNAs regulate PLK1 in breast cancer will improve our understanding of the PLK1 pathway, and whether this miRNA-directed regulation affects anti-PLK1 therapy. The work outlined here sets the stage for further inquiry into miRNA-governed pathways and their effects on drug response, something that should be considered carefully as putative targets are identified for (open full item for complete abstract)
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    Committee: Carlo Croce MD (Advisor); Larry Schlesinger MD (Committee Member); Kay Huebner PhD (Committee Member); William Carson MD (Committee Member) Subjects: Biology; Biomedical Research; Cellular Biology

  • 7. Lan, Shang-Lun Vitamin D in Normal Breast Tissue Correlates to Early Breast Carcinogenesis

    Doctor of Philosophy, The Ohio State University, 2016, Molecular, Cellular and Developmental Biology

    Vitamin D, the precursor to the potent steroid hormone calcitriol (1,25(OH)2D), is obtained through synthesis following sunlight exposure, diet and supplements. Vitamin D is first metabolized by CYP2R1 in the liver to produce calcifediol (25(OH)D), a circulating form of vitamin D, which is further converted to 1,25(OH)2D by CYP27B1 primarily in the kidney. 1,25(OH)2D can also be produced by extrarenal CYP27B1 in local tissues, including the breast, functioning in an intracrine, autocrine or paracrine manner. 1,25(OH)2D binds to the vitamin D receptor (VDR) that regulates multiple gene expression. However, most studies reported circulating 25(OH)D level but not the level of 1,25(OH)2D in the target tissue. Laboratory studies indicate that vitamin D should decrease the risk of breast cancer, although epidemiological studies are mixed. Thus, the potential anticancer mechanisms for women remain elusive. In the breast, little is known about the metabolic consequences of vitamin D at the cellular level and how this may potentially impact early breast carcinogenesis. In order to address these issues, blood and tissue samples from 153 healthy women undergoing reduction mammoplasty were used to examine 25(OH)D, 1,25(OH)2D levels and VDR protein expression. These women never had cancer, so findings from their breast tissue would represent biological processes before cancer develops, e.g. early carcinogenesis. I aimed to assess the correlation of blood to breast vitamin D levels, to assess the usefulness of blood levels of 25(OH)D in epidemiology studies as markers for breast levels of 1,25(OH)2D (aim 1), and if there were breast cancer risk factors that affected breast vitamin D levels (aim 2) (Fig. 1.4). I also aimed to determine if there were breast VDR (receptor) that positively correlated to 1,25(OH)2D and 25(OH)D (ligands) (aim 3). To investigate if breast vitamin D alone or with VDR affected breast pre-carcinogenesis, different markers were determined in normal breast (open full item for complete abstract)
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    Committee: Peter Shields (Advisor); Jeffrey Parvin (Committee Member); Gregory Lesinski (Committee Member); Michael Freitas (Committee Member) Subjects: Biomedical Research; Biostatistics; Endocrinology; Epidemiology; Molecular Biology; Oncology; Womens Studies

  • 8. Bejarano Buele, Ana Comparison of Radiation Treatment Plans for Breast Cancer between 3D Conformal in Prone and Supine Positions in Contrast to VMAT and IMRT Supine Positions

    Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2015, Biomedical Sciences (Radiation Oncology)

    The treatment regimen for breast cancer patients typically involves Whole Breast Irradiation (WBI). The coverage and extent of the radiation treatment is dictated by location of tumor mass, breast tissue distribution, involvement of lymph nodes, and other factors. The current standard treatment approach used at our institution is a 3D tangential beam geometry, which involves two fields irradiating the breast, or a four field beam arrangement covering the whole breast and involved nodes, while decreasing the dose to organs as risk (OARs) such as the lung and heart. The coverage of these targets can be difficult to achieve in patients with unfavorable thoracic geometries, especially in those cases in which the planning target volume (PTV) is extended to the chest wall. It is a well-known fact that exposure of the heart to ionizing radiation has been proved to increase the subsequent rate of ischemic heart disease. In these cases, inverse planned treatments have become a proven alternative to the 3D approach. The goal of this research project is to evaluate the factors that affect our current techniques as well as to adapt the development of inverse modulated techniques for our clinic, in which breast cancer patients are one of the largest populations treated. For this purpose, a dosimetric comparison along with the evaluation of immobilization devices was necessary. Radiation treatment plans were designed and dosimetrically compared for 5 patients in both, supine and prone positions. For 8 patients, VMAT and IMRT plans were created and evaluated in the supine position. Skin flash incorporation for inverse modulated plans required measurement of the surface dose as well as an evaluation of breast volume changes during a treatment course. It was found that prone 3D conformal plans as well as the VMAT and IMRT plans are generally superior in sparing OARs to supine plans with comparable PTV coverage. Prone setup leads to larger shifts in breast volume as well as in pos (open full item for complete abstract)
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    Committee: E. Parsai PhD (Advisor); D. Shvydka PhD (Committee Member); K. Reddy MD, PhD (Committee Member) Subjects: Medicine; Oncology; Physics; Radiation

  • 9. Machaj, Agnieszka Breast Cancer in PTEN Hamartoma Tumor Syndrome: Can a Predictive Fingerprint be Identified?

    Master of Sciences, Case Western Reserve University, 2014, Genetic Counseling

    Breast carcinoma is a primary malignant tumor occurring in PTEN Hamartoma Tumor syndrome (PHTS). PHTS is caused by germline mutations in the tumor suppressor gene PTEN. Little is known about the histopathologic features and molecular profile of PHTS-related breast cancers. Furthermore, no data have been published on blood-PTEN/pAKT protein expression in individuals with germline PTEN mutations or other potential predictors of PTEN mutation status. Histopathological review of original Hematoxylin and Eosin slides demonstrated that apocrine features, atypical apocrine adenosis, and atypical ductal hyperplasia are distinctive histopathological features of PHTS-related breast tumors. A distinct PHTS-associated molecular profile was not identified; the association of PHTS-related breast cancers with a molecular apocrine profile was not confirmed. Furthermore, we determined that low blood-PTEN protein and/or high blood-pAKT expression, as well as the Cleveland Clinic PTEN risk score, may be used as predictors of germline PTEN mutations in Cowden syndrome/CS-like presentations of breast cancer.
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    Committee: Anne Matthews RN, PHD (Committee Chair); Anna Mitchell MD, PhD (Committee Member); Michell Merrill MS, CGC (Committee Member); Jessica Mester MS, CGC (Committee Member); Charis Eng MD, PhD (Committee Member) Subjects: Genetics

  • 10. Senff, Sarah IN SEARCH OF A POLYPHONIC COUNTERNARRATIVE: COMMUNITY-BASED THEATRE, AUTOPATHOGRAPHY, AND NEOLIBERAL PINK RIBBON CULTURE

    Master of Arts, Miami University, 2013, Theatre

    This thesis uses practice-based research to explore possible interventions into the traumatic impact of illness upon breast cancer survivors' voices and the role of neoliberal pink ribbon culture in compounding their silencing. The interdisciplinary research pulls from the fields of applied theatre, critical pedagogy, materialist feminism, narrative analysis, social movement theory, medical sociology, and dialogue, disability and performance studies. Reflecting upon process and praxis relating to a regional tour of Susan Miller's My Left Breast as a means to engage a community of survivors, advocates and the general public, this thesis asks: Can a community-based theatre event focused on exploring breast cancer counternarratives provide both a therapeutic space for survivors to tell their stories as well as encourage the audience to think more critically about how culture works to influence narratives emerging from breast cancer culture?
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    Committee: Ann Elizabeth Armstrong (Advisor); Paul Jackson (Committee Member); Ann Fuehrer (Committee Member) Subjects: Fine Arts; Medical Ethics; Pedagogy; Performing Arts; Theater; Theater Studies; Womens Studies

  • 11. Yaghjyan, Lusine Determinants of Mammographic Breast Density in Different Subsets of Women

    PhD, University of Cincinnati, 2009, Medicine : Epidemiology (Environmental Health)

    Mammographic breast density is a strong predictor of breast cancer. The current retrospective study determines if the direction and degree of the association between risk factors for breast density and the breast density phenotype differ in the subsets of women stratified by menopausal status, hormone replacement therapy use (HRT), and family history of breast cancer. The study participants were selected from women enrolled in the Fernald Medical Monitoring Program (FMMP). To be included in the study, women were required to have been enrolled in FMMP as adults, be Caucasians, and have had at least one mammogram in FMMP mammography database. Women who had any diagnosis of breast cancer, genetic syndromes and disorders with underdevelopment of breast and small stature, history of mammoplasty, or were transsexual were not eligible for the study. Discordant phenotypes for mammographic breast density (high breast density [cases, N=265] and low breast density [controls, N=860]) were defined using the mammographic breast density assessment from the original radiologists' readings. The earliest FMMP screening or diagnostic mammogram that had criteria used to define the density phenotype was used as an index mammogram if the woman was 40-80 years old at the time of the index mammogram and had a Body Mass Index (BMI)<35 at the time of the mammogram. The data were analyzed using SAS Statistical Software. Findings of this study suggested a statistically significant effect of parity (protective) and alcohol use (direct) on breast density. A significant effect of age on breast density was limited to 50-<60 year old women. When stratified by menopausal status, BMI showed a significant protective effect and ever use of alcohol showed a significant direct effect on breast density phenotype in premenopausal women, while in postmenopausal women, parity showed a significant protective effect and a family history of breast cancer, age, and HRT use had direct effects on the breast densi (open full item for complete abstract)
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    Committee: Susan Pinney PhD (Committee Chair); Mary Mahoney MD (Committee Member); Paul Succop PhD (Committee Member); Ranjan Deka PhD (Committee Member); Sohaib Khan PhD (Committee Member) Subjects: Epidemiology

  • 12. Olson, Amanda The Narrative Construction of Breast Cancer: A Comparative Case Study of the Susan G. Komen Foundation and National Breast Cancer Coalisions' Campaign Strategies, Messages, and Effects

    Doctor of Philosophy (PhD), Ohio University, 2005, Communication Theory and Process (Communication)

    The goal of this research is to reveal the connections, contradictions, tensions, and paradoxes inherent in the narratives of breast cancer created by the Susan G. Komen Breast Cancer Foundation and the National Breast Cancer Coalition by exploring three research questions: Q1: How do the Susan Komen Breast Cancer Foundation and the National Breast Cancer Coalition perform a narrative of breast cancer at their respective events? Q2: How are these performed narratives shaped by the cultural and historical context of breast cancer awareness in the United States? Q3: How do these performed narratives shape current breast cancer awareness in the United States. In addressing these questions, the historical and cultural roots of breast cancer campaigns in the US are addressed, as well as current narrative health communications scholarship. The organizational stories are told through ethnographic thick descriptions and analyzed using Goffman's Frame Analysis to reveal narrative structure, cultural and historical themes, and speculate about the future of breast cancer awareness efforts in the US. This study serves as a record of events, a model of culturally and historically based narrative research, and a demonstration of how narrative theories can extend beyond the scope of a single author and explain collective authorship as well. Reframing narrative scholarship in this way expands on current theories and offers a new perspective for analyzing the ways that we communicate about health-based narratives.
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    Committee: Nagesh Rao (Advisor) Subjects: Speech Communication

  • 13. Richardson, Carlyn Psychosocial associations of mammography screening: An exploratory analysis using the Health Information National Trends Survey (HINTS) 2005

    Master of Science, Miami University, 2011, Family and Child Studies

    This study examined compliance in mammography screening among a sample of African American and Caucasian women aged 40 and over, using data from the 2005 Health Information National Trends Survey (HINTS). The socio-ecological model helped to identify the psychosocial associations that influence breast cancer screening. Compared to Caucasian women, African American women reported significantly higher psychological distress (M=1.7, SD=.69; M=1.9, SD=.84, respectively). Logistic regression indicated that race (z = 5.556), age (z = 22.933), household income (z = 8.398), health coverage (z = 6.772), and having a family history of breast cancer (z = 5.167) have significant predictive contributions to compliance.
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    Committee: Sherrill Sellers PhD (Committee Chair); Elise Radina PhD (Committee Member); Rose Marie Ward PhD (Committee Member) Subjects: Behaviorial Sciences

  • 14. Li, Dandan Patient-Centered Model for Predicting Distant Metastasis in Breast Cancer: Insights from the 2021 National Inpatient Sample (NIS)

    MS, University of Cincinnati, 2024, Medicine: Biostatistics (Environmental Health)

    Abstract Background: Breast cancer remains a leading cause of cancer-related morbidity and mortality in women worldwide. Traditional methods for predicting metastasis in breast cancer rely primarily on tumor pathology characteristics, such as tumor size, TNM grade, and receptor status. However, these methods do not fully account for patient-centered health factors, which could also play a role in metastasis risk. Factors such as a patient's overall physiological health, history of anti-neoplastic treatments, and personal and family history of cancer may also significantly impact the likelihood of developing distant metastasis in breast cancer. This study aims to develop a predictive model for distant metastasis in breast cancer that incorporates these broader, patient-centered factors for a more comprehensive risk assessment. Methods: This study analyzed all 4296 female breast cancer cases from the 2021 NIS, assessing 130 variables. Among these cases, 1691 (39.36%) had distant metastasis, while 2605 (60.64%) did not. For metastasis prediction, 21 key variables were selected, including age, race, anti-neoplastic treatment, presence of other cancers, cancer history, smoking, depression/anxiety, elective admission, All Patient Refined DRG Severity of Illness Subclass (APRDRG Severity), and various comorbidities. A binary logistic regression model was developed to build the predictive model for distant metastasis in breast cancer, and refined through backward elimination with cross-validation used for validation. Additionally, eight additional variables, such as morbidity, length of stay, and total charges were analyzed for comparison but were not included in the predictive model. Statistical comparisons between metastatic and non-metastatic groups were conducted, with continuous variables assessed using the Mann-Whitney U test and categorical variables using the Chi-Square test or Fisher's Exact test. The significance level (a) was set at 0.05. All analy (open full item for complete abstract)
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    Committee: Roman Jandarov Ph.D. (Committee Member); Marepalli Rao Ph.D. (Committee Chair) Subjects: Biostatistics

  • 15. Maldonado, Gabriela Using geographically weighted regression to explore the relationship between late-stage diagnosis of breast cancer and accessibility to breast cancer screening centers in the Chicago metropolitan region /

    Master of Arts, The Ohio State University, 2008, Graduate School

    Committee: Not Provided (Other) Subjects:

  • 16. McLaughlin, John Patient and provider determinants associated with the prescription of adjuvant hormonal therapies following a diagnosis of breast cancer in medicaid enrolled patients /

    Master of Science, The Ohio State University, 2007, Graduate School

    Committee: Not Provided (Other) Subjects:

  • 17. Dignan, Stephen A Comparison of Logistic PCA and Selected Data Embedding Procedures for Binary Data with Application to Breast Cancer and Glioblastoma Data

    Master of Science, The Ohio State University, 2024, Statistics

    Principal component analysis (PCA) is a data analysis technique used to reduce the dimension of a data set while retaining key patterns of variation by transforming the data to a lower-dimension space defined by orthonormal basis vectors that capture the directions of maximal variation. A novel technique named logistic PCA (LPCA) was developed that allows researchers to make use of benefits of PCA analysis in the study of data sets containing binary variables, allowing for more widespread use of these methods in areas of study frequently examining binary data, such as biomedical science and healthcare. We apply logistic PCA method to two data sets, the first comprised of data from tissue samples obtained from patients diagnosed with breast cancer and the second comprised of data from select genetic profiles of individuals diagnosed with brain tumor. An initial simulation study was performed to examine randomly-generated binary data from settings with a known clustering structure to evaluate retention of clustering in low-dimension plots created using PCA, LPCA, and t-distributed stochastic neighbor embedding (t-SNE), another frequently-utilized data analysis technique. Results revealed that LPCA consistently outperforms PCA in terms of reconstruction error in settings where probability parameters for clusters are close to 0.5 and that LPCA and PCA perform comparably in settings with more extreme probability parameters. LPCA and t-SNE also show comparable clustering in the two-dimensional plots. In analysis of the cancer-related data, two-dimensional plots for data embedding were generated, and principal component loadings were obtained from each of the data sets using LPCA and PCA, and used to provide interpretations of data patterns in the context of cancer-related biomedical science and healthcare. Analysis revealed that interpretations of LPCA loadings provide information consistent with established biomedical research findings as well as new information and that (open full item for complete abstract)
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    Committee: Yoonkyung Lee (Advisor); Asuman Turkmen (Committee Member) Subjects: Applied Mathematics; Biology; Genetics; Medicine; Oncology; Statistics

  • 18. Sridharan, Sangita The Role of Eukaryotic Translation Initiation Factor 4A1 in Breast Cancer Chemoresistance

    Doctor of Philosophy (PhD), University of Toledo, 2020, Biomedical Sciences (Cancer Biology)

    Chemoresistance is a major clinical concern in triple-negative breast cancer (TNBC) patients, leading to minimal residual disease and tumor relapse. Intrinsic chemoresistance is mediated by the surviving breast cancer stem-like cells (BCSCs) that self-renew and undergo multilineage differentiation to repopulate into a heterogeneous tumor. BCSCs are not only intrinsically chemo/radio resistant, but can also interconvert between BCSCs and bulk tumor cells. In addition to intrinsic therapy resistance, cancer cells can also acquire resistance when they are gradually exposed to therapy, which is the usual course of a treatment regimen. During this process, cancer cells continuously adapt and rewire or reprogram themselves and their microenvironment by upregulating drug transporter proteins and survival factors for their sustenance. Therefore, it is imperative to identify novel molecular targets and develop therapeutic strategies that could co-target BCSCs and bulk tumor cells to tackle both, intrinsic and acquired chemoresistance. Many oncogenic signaling pathways converge at the eukaryotic protein translation initiation machinery, the eIF4F complex which plays a key role in regulating the translatome. This complex plays a critical role in translation of several oncogenic mRNAs implicated in cellular proliferation, invasion, metastasis and chemoresistance. In our previous study, we demonstrated that the mRNA helicase eIF4A1 of the eIF4F complex, serves as a vulnerable node in inducing cell-death in TNBC cells. In our current study, we hypothesized that targeting eIF4A1 could be used as a strategy to overcome breast cancer chemoresistance. We developed two model systems; BCSCs and paclitaxel-resistant cells, reflective of intrinsic and acquired chemoresistance. Through pharmacological (Rocaglamide A) and genetic (CRISPR-Cas9) targeting of eIF4A1, we observed a statistically significant reduction in the self-renewal ability, pluripotency factors and drug transporter expres (open full item for complete abstract)
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    Committee: Dayanidhi Raman (Advisor); Kathryn Eisenmann (Committee Member); Saori Furuta (Committee Member); Nagalakshmi Nadiminty (Committee Member); Amit Tiwari (Committee Member) Subjects: Biomedical Research

  • 19. Weber, Zachary Applications of ctDNA Genomic Profiling to Metastatic Triple Negative Breast Cancer

    Master of Science, The Ohio State University, 2020, Public Health

    Breast cancer is the most common form of cancer among women. Triple negative breast cancers are a particularly aggressive subtype of breast cancer, accounting for an outsized proportion of disease related deaths. Metastatic TNBC is not curable and has limited options for palliative treatments, relying on a series of carefully managed monotherapies to slow disease progression. Advances in monitoring techniques may aid in the management of therapies in the metastatic context, as well as provide additional, actionable information on emergent biomarkers and targetable sites. In this work, we detail the application of PyClone, a hierarchical-Bayes framework for modeling clonal cell populations in cancer, to deep targeted panel sequencing of circulating tumor DNA, derived from serum collected in the phase-II biomarker study of cabozantinib in mTNBC. We demonstrate that important lesions can be tracked simultaneously through as many as eight time points in treatment, and that these lesions can be modeled into representative clonal populations, despite data sparsity. Our findings indicate that individuals can display markedly different clonal dynamics over similar windows of time, with identical diagnoses and treatments. Modeling variant populations gives us limited but valuable insight into phylogenetic origins of tumor clone populations. We also observe discordance between prognostic tumor fraction estimates of ctDNA and RECIST response categories, as well as demonstrate the ability to use whole exome sequencing of ctDNA to make computational predictions on the emergence of novel neoantigens throughout the course of treatment. Our successful application of these technologies suggests that ctDNA-based genomic profiling is an under-utilized tool for the study of cancer evolution, response to therapy, and disease progression monitoring. We suspect that ctDNA-based genomic profiling may provide valuable information through minimally invasive means in translational cancer rese (open full item for complete abstract)
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    Committee: Courtney Hebert MD MS (Advisor); Chi Song PhD (Committee Member); Daniel Stover MD (Committee Member) Subjects: Biology; Biomedical Research; Cellular Biology; Evolution and Development

  • 20. Haynam, Marcy Feasibility and Preliminary Efficacy of a Community-Based, Lifestyle Intervention on Select Body Composition, Functional, and Quality of Life Outcomes Among Breast Cancer Survivors

    Master of Science, The Ohio State University, 2020, Kinesiology

    Breast cancer survivors are a unique cancer population in that they are having success in treatment but are experiencing the negative side effects that various treatments cause, whether it be soon or very long after treatment. As a result of advances in treatment, less and less breast cancer survivors are dying from of their disease. Instead, their mortality is caused by the other conditions that they become at risk for from the treatment effects. Weight gain is an example of one of these side effects that is seen in breast cancer survivors that places these individuals at risk for poor cardiovascular and metabolic health. The combination of benefits seen from engagement in physical activity and dietary behavior change could lend itself to an optimal approach to mitigate the detrimental side effects that we see, especially weight gain. The lifestyle weight management literature in breast cancer survivors has shown that physical activity can be performed safely and effectively, and the inclusion of diet aids in further improvements in weight management. With the increased knowledge and community support for breast cancer survivor programming, assessing the feasibility and preliminary efficacy of a community-based lifestyle weight management intervention will assist in addressing the lack of community access that currently exists for breast cancer survivors after their treatment. The purpose of this study is to determine the feasibility and preliminary efficacy of a community-based lifestyle weight management intervention in breast cancer survivors on select body composition, physical function, and quality of life outcomes during the first 3 months of the first wave of the Healthy New Albany Breast Cancer (HNABC) pilot trial. The 24-week, HNABC study is held at a community center and promotes lifestyle behavior changes through a group-mediated cognitive behavioral (GMCB) approach driven by Social Cognitive Theory, in hopes of producing meaningful results for feasibili (open full item for complete abstract)
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    Committee: Brian Focht (Advisor); Maryam Lustberg (Committee Member) Subjects: Behavioral Sciences; Behaviorial Sciences; Cognitive Therapy; Health Sciences; Kinesiology; Nutrition; Oncology