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Prof. Dr. Maria Katapodi

Department of Clinical Research
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«Comparing Natural Language Processing (NLP) with Qualitative Research Methods to Understand Coping Mechanisms of HBOC-affected Women»

Research Project  | 2 Project Members

Carrying a pathogenic variant associated with hereditary breast ovarian cancer (HBOC) and subsequently developing an HBOC-associated cancer triggers a variety of emotional reactions and places extraordinary demands on women's coping abilities. My goal is to better understand how these women cope with their specific situation by applying machine learning techniques via natural language processing (NLP). To study individual coping mechanisms, I will use narrative data derived from qualitative interviews with female HBOC-mutation carriers that have been conducted within the CASCADE and DIALOGUE studies in German, French and Italian, as well as additional interviews that I will conduct within this study. Furthermore, I will have access to narrative data from 150 interviews that have been conducted at Boston College, US, and focus on HBOC-affected women, genetic testing, and coping. The transcripts will be analyzed with both natural language processing techniques (NLP, sentiment analysis) and traditional qualitative methods (grounded theory method after Strauss and Corbin, constant comparative method after Glaser) with the aim to identify individual stressors and coping mechanisms of female HBOC-mutation carriers. I will explore if NLP methods can generate codes that support or augment qualitative codes, and if NLP is able to simplify and partially replace traditional qualitative analyses. By clarifying HBOC-carrying women's individual needs and coping strategies, healthcare professionals and therapists will be able to better support them during vulnerable and demanding times related to treatment decision-making, family communication regarding the pathogenic variant, and maintaining an equilibrium between social, family, and potentially professional roles.

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The CASCADE II Study

Research Project  | 17 Project Members

Several hundred cancer patients in Switzerland carry pathogenic germline variants associated with hereditary breast/ovarian cancer (HBOC) and Lynch syndrome (LS). HBOC and LS cases are at significantly higher risk of primary and secondary cancers and need lifelong cancer surveillance and access to different risk management options. Their close blood relatives have 12.5%-50% probability of inheriting the respective cancer predisposition and need access to genetic evaluation. European-based studies suggest that most cancer patients with hereditary cancer syndromes are not identified and do not receive adequate cancer surveillance. Most evidence comes from cross-sectional studies; there is little available information about changes in adherence to surveillance over time. Little is known about how genetic test results affect subsequent surveillance for HBOC and LS cases and blood relatives, and the overall response of the Swiss healthcare system to mutation carriers' and relatives' needs for long-term surveillance and cancer prevention. CASCADE II will collect prospective three-year data from confirmed mutation carriers and blood relatives to examine how cancer surveillance practices, uptake of risk management options, and access to genetic services (for untested relatives) change over time. Specific Aim 1: Monitor changes over time in cancer status, surveillance practices, uptake of risk management options, and uptake of genetic testing (for previously untested relatives), and explore whether there are differences in occurrence of these events (or cumulative incidence of events) during the follow-up period among the different participant groups. Specific Aim 2: Examine the predictive value of individual domain clusters (e.g., cancer status), interpersonal domain clusters (e.g., family environment), and healthcare system domain clusters (e.g., provider specialty) on cancer surveillance practices, uptake of risk management options, and uptake of genetic testing (for previously untested relatives). Specific Aim 3: Explore participants' preferences for the role and involvement of healthcare providers in organization of cancer surveillance and follow-up care. Longitudinal data from the CASCADE cohort, a prospective, family-based cohort targeting HBOC and LS confirmed cases and blood relatives will address these aims. CASCADE uses surveys to assess cancer status, surveillance, management of hereditary cancer risk, and coordination of care, covering multi-level factors affecting cancer prevention and survivorship. Data from the CASCADE I and CASCADE II studies span a period of over 6 years and 4 data collection points, each approximately 18 months apart, for participants entering the cohort since its initiation. Recruitment takes place in oncology and/or genetic testing centres in three linguistic regions of Switzerland. Longitudinal survey data will address Aims 1 and 2. We will use Kaplan-Meier analyses and multivariate and/or multi-level Cox Proportional Hazards models to regress "cancer surveillance" event and "use of genetic services" event on predictors. Exploratory factor analyses and hierarchical cluster analyses will generate domain clusters for participants. Narrative data (focus groups and interviews) from selected participants to present diverse perspectives, triangulated with survey data, will address Aim 3. Data from the CASCADE cohort have considerable potential to enhance the development of high-quality comprehensive support systems to improve cancer surveillance and access to genetic specialists and coordination of cancer care services in Switzerland.

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Machine learning techniques for personalized breast cancer prognosis - Swiss BCpro

Research Project  | 6 Project Members

Early detection of breast cancer through screening and the advent of new treatments has contributed greatly to disease survival. This, in turn, elevates the importance of disease prognosis i.e., survival and cancer recurrence. A prognostic model with increased ability to classify patients into different risk groups and estimate overall survival time can influence choice of treatment and can spare patients from unnecessary treatments. Clinicians can offer patients individualized treatment and disease management strategies if a reliable and accurate prognostic model is available and has been incorporated in clinical practice. Most patients also desire information about their prognosis and overall survival. Researchers can design more efficient and ethical clinical trials by using accurate prognostic models to stratify patients. Finally, prognostic models have a great impact on health policy and allocation of social resources among cancer survivors. In the past two decades, several models have been developed for breast cancer prognosis. However, most models have been developed to test the prognostic value of a specific biomarker or to compare methods for model development, rather than to support clinical decision-making. Few models went through the complete translational pathway from preclinical development, validation, to the evaluation of clinical usefulness, such as the improvement of clinical decision-making. Only one model, which can classify patients into two risk groups (Dying vs. Surviving) was tested for "clinical usefulness". However, classifying patients into two groups cannot reflect its usefulness in clinical settings, since there are numerous treatments, treatment decisions are based on various factors and often change over time. A clinically useful prognostic model should be able to classify patients into multiple risk groups so that it can have mutual corroboration with treatment options and guidelines. The model eventually needs to be accessed in a randomized control trial, testing whether using the model to classify patients into different risk groups and informing treatment decisions improves survival or other patient reported outcomes. . Finally, the performance of current models varies across different populations. No model was developed with patients from Switzerland, validated for the Swiss population, or has been evaluated for clinical usefulness in Swiss clinical settings. Machine learning offers an alternative approach to classical model-based prediction e.g. Cox proportional hazard (PH) regression. It can address limitations of classical modeling and improve accuracy from 70% of Cox PH models to about 85%. A machine learning-based prognostic model learns from real world data where more than 20% breast cancer treatment decisions disagree with clinical guidelines and change over time. It can classify breast cancer patients into multiple risk groups, and also generate risk predictions based on different treatments. The treatment-specific stratification can inform treatment decision-making. However, no machine learning-based breast cancer prognostic model has been validated in independent populations for generalizability, and no machine learning-based model was tested for clinical usefulness, such as supporting clinical decision-making. We aim to create a machine learning-based breast cancer prognostic model, the Swiss-BCpro, to support personalized management of breast cancer with data collected from Swiss cancer registries. The specific aims are 1. to develop the Swiss-BCpro by using machine learning to analyze data available in the Geneva cancer registry; 2. to compare the calibration and predictive accuracy of Swiss-BCpro with other state-of-the-art models for breast cancer prognosis i.e., PREDICT, NPI, CancerMath; 3. to externally validate Swiss-BCpro with independent data from the cancer registries of Zurich and St. Gallen; 4. to explore its clinical usefulness, namely comparing the clinical utility of Swiss-BCpro stratification with both guideline-based clinical decision-making and actual treatments patients received. The study will contribute to the personalized management of breast cancer patients in Switzerland by translating machine leaning-based breast cancer prognostic modeling into clinical practice.

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SOLACESOLACE: Cost-effectiveness of palliative care for patients and their caregivers in resource-limited settings in the Republic of Kazakhstan

Research Project  | 2 Project Members

Quality of life of caregivers of cancer patients is lower compared with the quality of life of caregivers of chronic disease patients. Moreover, no research assessing quality of life of caregivers have been conducted in Central Asia and in Kazakhstan, where lack of trained personnel; limited hospice and palliative beds availability; and underdevelopment of in-home and outpatient day-care services exist. Aims: To assess the state of palliative care in the Republic of Kazakhstan within the past 5 years. To assess the effectiveness of palliative care on cancer patients' and their caregivers' quality of life, patients' length of stay, and caregivers' mental health and bereavement. To assess the cost-effectiveness of inpatient hospice-based palliative care services for cancer patients in the Republic of Kazakhstan. Methods Sample: Data collection will be conducted in all five hospices across Kazakhstan. A total of 100 hospice patients with clinically terminal cancer will be given consent and asked to fill out the survey with or without help from their family caregivers. In addition, 50 healthcare professionals and 50 family caregivers will be surveyed and interviewed privately in their offices/rooms. Design: The proposed study will use retrospective and prospective data involving quantitative and qualitative mixed-methods research, where integration of individual semi-structured in-depth interviews, a cross-sectional survey and analyses of existing data will be conducted. The financial impact of palliative care will be estimated using the incremental cost-effectiveness ratio. Finally, to check variations in outcomes under a given set of assumptions, a sensitivity analysis will be conducted. Data collection and analyses: The short form surveys will be administered to assess quality of life of patients and caregivers. The quality-adjusted life years (QALYs) indicator will be calculated using the analyzed results of the survey and the average life expectancy of each participant as obtained from the WHO life-tables. R software, version 3.6.0. (r-project.org) will be used for conducting data checking, cleaning and computing total scores. The NVivo program will be utilized for qualitative analyses. Thus, after coding, a construction of emergent themes will be performed.

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The DIALOGUE Study: Using digital health to improve care for families with predisposition to hereditary cancer

Research Project  | 15 Project Members

In Hereditary Breast and Ovarian Cancer (HBOC) syndrome, communication of genetic test results with relatives is essential to cascade genetic screening. Cascade genetic screening is a sequential process of identifying and testing blood relatives of a known mutation carrier to determine if they also carry the pathogenic variant, in order to propose preventive and other clinical management options that reduce morbidity and mortality. However, according to Swiss and Korean privacy laws, individuals identified with the pathogenic variant have the sole responsibility to share information about test results and health implication to relatives. Empirical evidence suggests that up to 50% of biological relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively. Thus, interventions designed to help probands effectively communicate with relatives are critical for better management of hereditary cancer risk. Technology could play a significant role in facilitating communication and genetic education within HBOC families. Given the lack of well-developed digital health tools to assist individuals with genetic predisposition to cancer effectively communicate genetic information to their relatives, the study aims to develop a modern, scalable, mobile friendly digital health solution for Swiss and Korean HBOC families. The digital health solution will be based on the Family Gene Toolkit (FGT), a web-based intervention designed to enhance communication of genetic test results within HBOC families that has been successfully tested for acceptability, usability, and participant satisfaction. The study will also expand an existing research infrastructure developed in Switzerland, to enable future collaborative projects between Switzerland and Korea in this field. The Specific Aims of the project are: 1) Develop a digital health solution to support the communication of cancer predisposition among HBOC families, based on linguistic and cultural adaptation methods of the Family Gene Toolkit for the Swiss and Korean population 2) Develop the K-CASCADE research infrastructure in Korea by expanding an existing research infrastructure developed by the CASCADE Consortium in Switzerland 3) Evaluate the efficacy of the aforementioned digital solution on psychological distress and communication of genetic test results, as well as knowledge of cancer genetics, coping, decision making and quality of life 4) Explore the reach, effectiveness, adoption, implementation, and maintenance of the aforementioned digital solution The content for the digital health solution will be based on the FGT with linguistic adaptation to Korean, German, French and Italian, and will be made available for web and mobile access. Aim 1 will be achieved through focus groups in each country to better identify cultural context with 20 -24 HBOC mutation carriers and relatives and 6-10 healthcare providers involved in genetic services (counseling and testing). For Aim 2 , K-CASCADE, a Korean database of HBOC families (mutation carriers and relatives) will be created based on the Swiss CASCADE Consortium database, creating a lasting research infrastructure that will facilitate future collaboration, including the possibility to apply machine learning algorithms for prediction of breast and ovarian cancer risk. For Aim 3, feasibility and efficacy of the digital health solution against the comparison intervention will be assessed in a randomized trial, with a sample of 104 HBOC mutation carriers (52 in each study arm). Aim 4 will be achieved with survey and interview data collected from participating HBOC families and healthcare providers during all phases of the study. Dissemination strategies will also be generated to ensure sustainable use of the digital health solution. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Adaptation and implementation of culturally sensitive, digital health interventions that can facilitate communication processes within the family and enhance understanding of genetic cancer risk are extremely timely and relevant, given the expansion of genetic testing technology, the falling costs of genetic testing, and the increased pressure for integration of genetic knowledge in routine clinical care. The study would be one of the first resource-effective international research platforms to develop digital health solutions that can be scaled to large patient numbers and can be used in routine practice.

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B-CaSS - Breast Cancer Symptom Study: Cancer-related cognitive impairement

Research Project  | 3 Project Members

Early detection of breast cancer and advances in treatment have considerably increased the probability of survival for patients. However, patients who receive advanced treatments also experience short and long term side effects. Approximately 75% of breast cancer patients experience cancer related cognitive impairment (CRCI) prior to, during, or after treatment. CRCI remains a significant long-term problem for about 35% of breast cancer survivors. CRCI may interfere with patients' self-care activities, such as ability to adhere to treatment, manage side effects, and re-integrate into the workforce, which can have a negative impact on their quality of life. Current studies provide conflicting evidence about subgroups of breast cancer patient who might be at higher risk for experiencing CRCI. Little is known about the contribution of genetic variations in the catecholaminergic and serotonergic pathways in the development and severity of CRCI. Finally, although acupuncture is being recommended for the management of hot-flashes and pain in cancer patients, there is little evidence that acupuncture can contribute to the management of CRCI. The specific aims of this study are to: Identify subgroups of breast cancer patients who are at higher risk for CRCI (accounting for demographic characteristics and clinical predictors) during the first 6 months after surgery Explore associations between catecholaminergic and serotonergic genes with CRCI subgroup membership Evaluate the efficacy of acupuncture to reduce CRCI The aims of the study will be addressed with quantitative, prospective, longitudinal, observational data collected in the U.S. regarding symptom burden among breast cancer patients prior to surgery and up to 60 months post systemic treatment (Aims 1 and 2); Aim 3 will be addressed with data collected in Germany for a prospective, single blind, randomized, controlled, multi-group comparison trial, which examined the efficacy of acupuncture for alleviating multiple symptoms in breast cancer patients receiving radiotherapy. Studies from all over the world report CRCI in breast cancer patients, since treatment protocols are implemented almost identically in western countries. This project will bring the long-term management of CRCI among breast cancer patients to the forefront of personalized care, and provide a better understanding of possible contributions of genetic variations of common neurotransmitters (i.e., catecholamines and serotonin) increased CRCI burden. A non-pharmacological intervention (i.e., acupuncture) may prove efficacious and effective for alleviating CRCI. The study will contribute to precision medicine research in Switzerland.

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The CASCADE cohort: a family-based cohort for investigating the use and impact of genetic testing, and the development of comprehensive interventions for hereditary breast/ovarian and Lynch syndromes in Switzerland

Research Project  | 5 Project Members

Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. About 2-15% of incident cases are due to known pathogenic germline variants. Approximately 5% of breast cancer cases and 10-15% of epithelial ovarian cancer cases develop due to the BRCA genes, which are associated with Hereditary Breast and Ovarian Cancer (HBOC). Lynch syndrome (LS) accounts for about 2-5% of colorectal cancer and endometrial cancers, and increased risk for other cancers including ovarian and pancreatic. Germline pathogenic variants in the DNA Mismatch Repair (MMR) account for most LS cases. The availability of genetic services for HBOC and LS is a significant milestone for effective cancer prevention and control. Genetic counseling can educate patients and cancer-free individuals about cancer risk and management options according to mutation status. For every carrier of a pathogenic germline variant, first- and second-degree relatives and first cousins have increased probability of carrying the same mutation. Due to availability of genetic testing, blood relatives can be tested with 100% accuracy. Cancer predisposition cascade genetic screening is a sequential process of identifying and testing blood relatives of a known mutation carrier. Goals of cascade screening are to determine if untested relatives also carry the pathogenic variant and propose preventive and clinical management options to reduce morbidity and mortality, and to identify non-carrier relatives and exclude them from intensive medical interventions. This approach has been strongly supported by the Center for Disease Control and Prevention (CDC), Office for Public Health Genomics. In Switzerland less than 25% of cases indicative of HBOC or LS use genetic services, suggesting that many mutation carriers and their blood relatives may not benefit from advances in medical diagnostics. HBOC and LS patients can benefit from intensive surveillance, pharmacoprevention, and/or prophylactic surgery. Monitoring cancer surveillance of mutation carriers ensures adequate quantity and quality of cancer care and coordination of healthcare services. Moreover, penetrance of these pathogenic mutations varies, and is likely influenced by modifiable behavioral and psychosocial risk factors, such as smoking, alcohol, and unhelpful coping with cancerrelated stress (e.g., avoidance and withdrawal). However, information about practices related to cancer screening, risk reduction, and cancer surveillance, and about modifiable behavioral and psychosocial risk factors can be obtained only from prospective family-based studies. Currently, there are no family-based cohorts for HBOC and LS in Switzerland. This critical information will provide evidence across the full continuum of cancer risk and support the development of targeted risk modification and preventive interventions. The purpose of this application is to support the development of the CASCADE cohort, a Swiss- and familybased cohort enriched for hereditary cancer risk by including members of families harboring germline pathogenic variants associated with HBOC and LS. The CASCADE cohort will facilitate the collection of epidemiological, cancer surveillance, behavioral, and psychosocial data, which over time will assist in finding sustainable solutions and developing interventions that optimize the Swiss healthcare system in preventing, managing and treating HBOC and LS. This application is submitted on behalf of the Swiss Cancer Predisposition Cascade Screening (CASCADE) Consortium, an inter-professional research consortium with scientists from basic, clinical, and social science from the German-, French-, and Italian-speaking regions of Switzerland. The purpose of the consortium is to investigate the use and impact of genetic testing for HBOC and LS in Switzerland, and develop and disseminate comprehensive interventions to families harboring these pathogenic variants. Members of the consortium are excellent researchers, clinicians, and scholars in the fields of HBOC and LS in Switzerland and internationally, and their pioneering studies support the necessity of cancer predisposition cascade genetic screening for HBOC and LS.

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Swiss-PROMPT Swiss Personalized Breast Cancer Risk Prediction study

Research Project  | 5 Project Members

Hintergrund: Breast cancer affects about 12% of Swiss women. Predictive models are important in personalized medicine because they contribute to early identification of high-risk individuals, which in turn facilitates stratification of preventive interventions and individualized clinical management. However, existing models have limited discriminatory accuracy (0.6-0.7) and do not include some non-modifiable and modifiable breast cancer risk factors, e.g., mammography density and obesity. Zielsetzung: The purpose of the study is to provide clinical decision support for accurate, reproducible, and more reliable individualized forecasting of the absolute risk for breast cancer compared to currently used models e.g., Gail model and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). Design / Methode: We employed six different model-free machine-learning methods to predict absolute risk of breast cancer. Using independent training and testing data we quantified and compared the performance of machine-learning methods to the performance of the Gail model and BOADICEA using the following datasets (1) simulated, with no signal; (2) simulated, with artificial signal; (3) a random population-based sample of US breast cancer patients and their cancer-free female relatives (N=1232); and (4) a clinic-based sample of Swiss breast cancer patients and cancer-free women seeking genetic evaluation and/or testing at the Geneva University Hospitals (N=1700). Managing the massive, multi-source, incongruent and heterogeneous data includes data harmonization, model-free predictive analytics, and quantitative comparison of forecasting reliability. Erwarteter Nutzen / Relevanz (z.B. für Public Health): Advanced data-processing protocols are powerful tools to forecast personalized breast cancer risk and can help develop new and updated predictive models specified for Swiss women.

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CASCADE - Cancer predisposition cascade genetic screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland

Research Project  | 17 Project Members

Background: Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. Objective: Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. Methods: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. Results: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. Conclusions: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. Trial Registration: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt)

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Randomized trial to test the efficacy of two interventions designed to increase screening and use of genetic services in young breast cancer survivors and biological female relatives

Research Project  | 13 Project Members

Hintergrund: Over the past decades, advances in screening, detection, and treatment have led to a significant reduction in the number of breast cancer deaths in the United States. More specifically, Michigan had a 40% decrease in mortality rates between 1990 (11.9 per 100,000) and 2009 (7.1 per 100,000) among young women diagnosed with breast cancer. However, the Comprehensive Cancer Control Plan for Michigan and the Healthy People 2020 objective is to further "reduce the female breast cancer death rate". The study strives to accomplish this goal, specifically for female breast cancer survivors diagnosed at 25-45 years old and their female relatives who may also have an increased risk. Zielsetzung: The study has three aims: (1) To identify and survey 3000 female breast cancer survivors reported to the Michigan Cancer Surveillance Program who were diagnosed between the ages of 25-45 years (YBCS) and determine:(a) their breast cancer screening utilization; (b) perceived barriers and facilitators to screening; (c) willingness to participate in a small media, evidence-based intervention to increase breast cancer screening utilization; and (d) willingness to serve as a breast cancer screening advocate for their high-risk female relatives. (2) To identify and survey up to two unaffected first- and/or second- degree female relatives per breast cancer survivor and determine: (a) their breast cancer screening utilization; (b) perceived barriers and facilitators to screening; and (c) willingness to participate in a small media, evidence-based intervention to increase breast cancer screening utilization. (3) To compare the efficacy of two interventions on breast cancer screening utilization and other outcomes among YBCS and their high-risk female relatives. Design / Methode: This prospective randomized trial involved testing the efficacy of two printed interventions i.e., Targeted vs. Enhanced Tailored designed to increase screening and use of cancer genetic services. Participants were randomly assigned as family units (YBCS and her female relatives) to receive one of two intervention versions. Family units were mailed a self-administered baseline survey prior to receiving the intervention (Time 1). A self-administered follow-up survey was mailed to participants nine months post-intervention. Erwarteter Nutzen / Relevanz (z.B. für Public Health): The study enhanced cancer prevention, control, and efforts toward public health genomics interventions. The two intervention versions provide a successful platform for implemention of public health genomic interventions.