Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Standard mammography screening in age 50-69

Mammography outside official screening

Peeter Padrik, MD, PhD

Vahur Valvere, MD,PhD

This is a cohort study, applied research and T3 translational genomics to estimate the impact of genetic risk for breast cancer detection in the screening program. The study group base consists of 28 389 female participants, currently in the age-group 22-79, in the Biobank of Estonian Genome Centre. The study is aimed to demonstrate the usability of personalised approach for adjusting and stratifying screening recommendations, based on predicted genetic risk estimates for breast cancer in the situation, where the genome data could be available from all women who have given informed consent for that. The project includes both the detection of moderate and high hereditary breast cancer risk carriers as well as high risk polygenic risk-score (consisting several single nucleotide polymorphisms) carriers among healthy individuals for application of personalised prevention and screening strategies.

Personalised Risk-based Breast Cancer Prevention and Screening

Implementation of a Model for Personalised Risk-Based Breast Cancer Prevention and Screening

University of Tartu

North Estonia Medical Centre

Tartu University Hospital

Director of the Cancer Center

Nervous System Diseases

Infections

Behaviors and Mental Disorders

Immune System Diseases

Blood and Lymph Conditions

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Rare Diseases

Parkinson Disease

Dementia

Autoimmune Diseases

Alzheimer Disease

Leukemia

Leukemia, Lymphoid

Communicable Diseases

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphocytosis

Parkinsonian Disorders

Ganglion Cysts

Synovial Cyst

Basal Ganglia Diseases

Brain Diseases

Central Nervous System Diseases

Movement Disorders

Synucleinopathies

Neurodegenerative Diseases

Tauopathies

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Leukocytosis

Leukocyte Disorders

Chronic Graft Versus Host Disease

Familial Alzheimer Disease

Chronic Lymphocytic Leukemia

Individuals over the age of 40 attending to the Clalit HMO clinics in the North of Israel for regular blood tests.

Geffen Kleinstern

The aim of this proposal is to identify immune biomarkers, genetic risk, and the clinical consequences of low count monoclonal B-cell lymphocytosis (LC MBL), a common premalignant condition affecting up to 17% of European adults age\&amp;gt;40. LC MBL is a precursor to chronic lymphocytic leukemia (CLL), characterized by a circulating population of clonal B-cells. It is relatively understudied, despite emerging evidence of clinical consequences such as increased risk for life-threatening infections and lymphoid malignancies. Studies reported that male sex, age, family history of CLL, and CLL-susceptibility genetic loci were associated with LC MBL risk. These findings were reported in European ancestry individuals and have not been generalized to other thnicities. This study will provide this missing knowledge using a unique multi-ethnic Israeli population of Jews and Arabs that have one of the highest and lowest age-standardized incidence rates of CLL in the world, respectively, and characterized with different genetic backgrounds.

Risk and Clinical Consequences of Low Count Monoclonal B-cell Lymphocytosis (LC MBL)

Immune Biomarkers, Genetic Risk, and the Clinical Consequences of Low Count Monoclonal B-cell Lymphocytosis (LC MBL)

Blood samples will be screened for MBL using flow cytometry, while data on the various outcomes will be collected from electronic medical records from Clalit Health Services.

DNA will be extracted from the blood sample and sequenced.

Blood samples will be screened for MBL using flow cytometry, ethnicity and sex will be determined using a demographic questionnaire

Blood sample will be screened for MBL using flow cytometry, and immune biomarkers will be screened from plasma samples.

Other clinical conditions will be determined from electronic medical records from Clalit Health Services

Clalit Health Services, Haifa and West Galilee

Bnai Zion Medical Center

University of Haifa

Senior Lecturer

The group will discuss its views about how and when to talk about the risk of getting breast cancer. The focus group will be video recorded and the video recorded material will be later transcribed and carefully analyzed. In addition you will be asked to answer questions about yourself, such as education and marital status.

The focus group will last about 90 minutes. However, your involvement in this study will last from the time you join until you read over the summary of what happened during the focus group and return your comments. This should be approximately 2 months. Patient will complete a questionnaire and we estimate total time for completion to be approximately 7 minutes.

focus group & questionaire

Smita Banerjee, PhD

The purpose of this study is to first understand how MSKCC Clinical Genetics Service doctors talk to women with breast cancer about any genetic risks they might carry, and if they help women to think about what they might say, in turn, to their relatives, especially their daughters.

A second part of the study asks women for their opinions about when and how their daughters should be told about any genetic risks.

All of this will help us develop teaching methods to help our doctors improve the way they talk about genetic risk when women with breast cancer have adolescent daughters.

The Communication of Genetic Risk to Adolescent Daughters of Women With Breast Cancer

Monash University

Memorial Sloan Kettering Cancer Center

Gland and Hormone Related Diseases

Heart and Blood Diseases

Diabetes Mellitus

Heart Diseases

MeTree collects family health history data and generates risk scores and specific risk-based recommendation for preventive care to patients as clinical decision support.

MeTree collects family health history data and generates risk scores and specific risk-based recommendation for preventive care to providers as clinical decision support.

Software program collecting family health history and generating clinical decision support for risk-based preventive care

MeTree

Geoffrey S Ginsburg, MD PHD

Lori Orlando, MD

The outcome of this research will be a demonstration that family health history (FHH) risk data can be used efficiently to deliver more effective healthcare in geographically and ethnically diverse clinical care environments. Although FHH is a standard component of the medical interview its widespread adoption is hindered by three major barriers: (1) a dearth of standard collection methods; (2) the absence of health care provider access to complete FHH information; and (3) the need for clinical guidance for the interpretation and use of FHH. In addition, the time constraints of the busy provider and poor integration of FHH with paper medical records or electronic medical records (EMR) impede its widespread use. The investigators hypothesize that patient-driven and electronic collection of FHH for risk stratification will promote more informed decision-making by patients and providers, and improves adherence to risk-stratified preventive care guidelines. The study team will use an implementation sciences approach to integrate an innovative FHH system that collects FHH from patients. Intermountain Healthcare will provide the information technology expertise with EMR design to develop an innovative solution to a storage model standard for FHH data as well as a centralized standards-compliant open clinical decision support (OpenCDS) rule development architecture to analyze FHH and to generate evidence-based, individualized, disease risk, preventive care recommendations for both patients and providers.

Five health care delivery organizations will participate in this demonstration project: Duke University, the Medical College of Wisconsin, the Air Force, Essentia Health, and the University of North Texas Health Science Center. The study will take place in 'real world' clinical, socio-cultural, and demographically diverse (rural, underserved, academic, family medicine) care clinics (n=34) in 5 states (CA, MN, NC, WI, TX) that include genomic medicine 'early adopter' and 'naïve' sites, as well as those that are EMR-enabled and others that are not. The study team will recruit a minimum of 7000 English or Spanish speaking adults over a 3-year period and will capture process metrics and outcomes that are measured in the course of usual care. The goals are: 1) To optimize the collection of patient entered FHH in diverse clinical environments for coronary heart disease, thrombosis, and selected cancers, 2) to export FHH data to an OpenCDS platform and return CDS results to providers and patients (and to EMRs where relevant) and to explore the integration of genetic risk and FHH data at selected sites, 3) to assess the clinical and personal utility of FHH using a pragmatic observational study design to assess reach, adoption, integrity, exposure, and sustainability, and to capture, analyze, and report effectiveness outcomes at each stakeholder level: patient, provider, and clinic/system, and 4) to take a leadership role in the dissemination of guidelines for FHH intervention across in diverse practice settings.

Family Health History in Diverse Care Settings (FHH)

Family Health History in Diverse Care Settings

How many patients identified as meeting criteria for genetic counseling, how many providers ordered genetic counseling, and how many patients adhere to the provider recommendation at 1 year.

The study will assess satisfaction associated with using the MeTree tool via 3 months survey after completing the family health history collection. The participant were asked their level of satisfaction with their experience using the web-based portal to enter information for their provider before their appointment

The study will assess comfort associated with using the MeTree tool via 3 months survey after completing the family health history collection. The participant were asked if the MeTree program was easy to use

The study will assess anxiety associated with using the MeTree tool via 3 months survey after completing the family health history collection. The participant were asked if answering the questions made them anxious

The study will assess preparedness associated with using the MeTree tool via 3 months survey after completing the family health history collection. The participants were asked if they had enough information about some people in their family when completing MeTree

Evaluate physicians' perceptions of satisfaction, the MeTree tool's impact on work load and its effectiveness via survey and informal interviews at 3 months.

Evaluate which providers were successfully using MeTree in their clinical work flow and which patients are successfully using MeTree for their care. (surveys, monitoring of clinical workflow, patient recruitment reflects underlying clinic population)

Duke University

All-Cause Mortality and Serious Adverse Events were not monitored/assessed for either Arm/Group

MeTree collects family health history data and generates risk scores and specific risk-based recommendation for preventive care to patients as clinical decision support.

MeTree: Software program collecting family health history and generating clinical decision support for risk-based preventive care

MeTree - Patients

MeTree collects family health history data and generates risk scores and specific risk-based recommendation for preventive care to providers as clinical decision support.

MeTree: Software program collecting family health history and generating clinical decision support for risk-based preventive care

MeTree - Providers

MeTree collects family health history data and generates risk scores and specific risk-based recommendation for preventive care to Providers as clinical decision support.

MeTree: Software program collecting family health history and generating clinical decision support for risk-based preventive care

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

12 mo survey ended early w/ approved by Duke IRB. Sufficient data obtained to perform the scientific analysis; the overall status of the study is still active, not recruiting. Participant contact completed.

Dr. Lori A. Orlando, Director Program in Precision Medicine

Patients who met genetic counseling criteria

Patients who received Genetic Counseling Order

Patients adhered to provider's recommendation-1yr

Providers who placed Genetic counseling order

Patients who completed intervention and meeting criteria for genetic counseling

Number of Participants With Uptake of Genetic Counseling for Those at Risk of Hereditary Conditions at 1 Year

Superior

Above Average

Very Satisfactory

Somewhat unsatisfactory

Very Poor

Not Answered

Patients who completed 3 months post survey and reported their level of satisfaction

Number of Participants Reporting Satisfaction When Using the MeTree Tool

Do not know

did not answer

Patients who completed 3 months post survey and reported on their level of comfort

Number of Participants Reporting Comfort When Using the MeTree Tool

Did not answer

Patients who completed 3 months post survey and reported on anxiety with answering the questions

Number of Participants Reporting Anxiety When Using the MeTree Tool

Patients who completed 3 months post survey and reported on preparedness

Number of Participants Reporting Preparedness When Using the MeTree Tool

Consented providers who completed provider post implementation survey

Number of Physicians Who Gave Their Perceptions of Satisfaction and the MeTree Tool's Impact on Work Load

Number of Providers Who Were Successfully Using MeTree in Their Clinical Work Flow

MeTree collects family health history data and generates risk scores and specific risk-based recommendation for preventive care to patients and providers as clinical decision support.

MeTree: Software program collecting family health history and generating clinical decision support for risk-based preventive care

Providers using MeTree risk assessment program for clinical decision support

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Digestive System Diseases

Syndrome

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hereditary Breast and Ovarian Cancer Syndrome

Colorectal Neoplasms

Colorectal Neoplasms, Hereditary Nonpolyposis

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Familial Colorectal Cancer

Genetic counseling according to current clinical practice

Genetic counseling according to current clinical practice with the addition of an offer from health care provider to mail letters directly to eligible at-risk relatives.

At counseling, eligible at-risk relatives (who may benefit from disclosure of risk information) are listed on a specified protocol in collaboration between health care provider and the participant.

Standard care encouraging family-mediated disclosure of hereditary cancer risk

The participant is offered that the health care provider at the cancer genetic unit mail a direct letter with personalized family risk information to all at-risk relatives that participant approve contact with.

Offer of health-care assisted disclosure by sending direct letters to at-risk relatives

This study evaluates if uptake of genetic counselling in high-risk families is increased when patients at cancer genetics clinics are being offered healthcare-assisted disclosure to at-risk relatives compared to current standard care (with family-mediated disclosure).

Patients/families who have undergone a cancer genetic investigation will be invited to participate in the study. All participants will receive standard care. Half of them will in addition be offered a healthcare-assisted disclosure with the service of direct letters to identified at-risk relatives distributed by the healthcare provider. After a year we will compare the proportion of at-risk relatives who have contacted a cancer genetic clinics in each study arm.

(When the formal study protocol is published, this section will instead refer to the published study protocol).

This study is a multi-centre open label, prospective, randomized controlled superiority trial comparing an intervention of healthcare-assisted disclosure with standard care of family-mediated disclosure of hereditary cancer risk information in high-risk families in Sweden.

SUBJECTS AND METHODS

Patients/families will be enrolled and allocated in parallel to intervention or standard care.

All participants receive standard genetic counseling and information summarizing the results of their family investigation. They are informed about preventive measures when applicable, and are encouraged to inform their at-risk relatives (t=0 months).

The intervention component is the addition of a healthcare-assisted disclosure procedure. Participants in the intervention arm will be offered the service of sending letters directly to their at-risk relatives.

If the participant approves the offer, letters will be sent to eligible at-risk relatives deemed to be recommended genetic counseling within a year.

The direct letter will inform the at-risk relative that a cancer genetic investigation has been conducted in the family and the implications for him or her, and their blood relatives.

To facilitate access to further information, contact details to the closest cancer genetics unit are included in the letter. The letters are sent with registered mail in neutral envelopes which means that recipients will have to show proof of identity to retrieve the letter from their local delivery service provider.

METHODS FOR ASSESSMENT OF STUDY OUTCOMES

For participants in both study arms, contact details of the at-risk relatives are identified in collaboration between health care provider and the participant. The health care provider records the name, approximate or exact year of birth and postal address of each at-risk relative for follow-up.

At the time of follow-up (t=12 months) the research nurse will check whether the relatives, listed one year before, have contacted a Swedish cancer genetic unit. Primary outcome data is retrieved from the patient data registries at each clinic. The research nurse will also record additional data points from CRFs, enabling analysis of the other pre-specified outcome measures in the intervention arm.

The outcome data are reported back to the national study secretariat as plain numbers without any personal details of the at-risk relatives.

SAMPLE SIZE AND STATISTICAL METHODS

For sample size calculation and statistical methods, see attached documents.

INTERNAL PILOT, AUDIT and PROGRESS CRITERIA

As this protocol has never been tested in Swedish clinical practice an internal pilot phase is included in the outline of the project.

Progress criteria at each study site are evaluated at internal pilot point and thereafter at formal audit at least yearly. Internal pilot point is set to the time when 20 individuals in total (across the 3 pilot study sites) have been included and treated according to protocol.

Continuation of the full-powered study at the specific study site will be determined by considering the criteria filled, the potentially necessary amendments, and the degree of which the amendments deviate from the original piloted study protocol.

The outcomes and process criteria are found in the attached document.

Multi-centre, parallel assignment, balanced ratio, investigator-blinded, randomised, controlled superiority trail in Sweden.

Since the intervention in this trial is an offer of sending physical direct letters to at-risk relatives, neither the health care providers nor the study participant can be blinded to the allocation. However, the final data analysis will be performed by a statistician blinded to the study arm allocations and subgroups.

Direct Information to At-risk Relatives

Direct Letters to Relatives at Risk of Hereditary Cancer- a Multi-centre Randomised Controlled Trial of Healthcare-assisted Versus Family-mediated Risk Disclosure at Swedish Cancer Genetics Clinics (DIRECT-study)

Access to aggregated data may be granted upon reasonable request to the principal investigator.

Comparing intervention and control group with respect to proportion of first-degree ARRs who have contacted a Swedish cancer genetics clinic within 12 months of the proband receiving post-test genetic counselling because the proband is a carrier of a pathogenic variant in BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2.

Comparing intervention and control group with respect to proportion of second-degree, third-degree or more distant ARRs who have contacted a Swedish cancer genetics clinic within 12 months of the proband receiving post-test genetic counselling because the proband is a carrier of a pathogenic variant in BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2.

Number of potential at-risk relatives that proband allowed contact with, compared to total number of potential at-risk relatives for that specific patient. \[proportion\]

Number of at-risk relatives that proband allowed contact with and where contact data allowed distribution of direct letter, compared to total number of potential at-risk relatives for that specific patient. \[proportion\]

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Personalised Risk-based Breast Cancer Prevention and Screening	NCT03989258	Breast Cancer	Mammography out...	25 Years -	Tartu University Hospital
Risk and Clinical Consequences of Low Count Monoclonal B-cell Lymphocytosis (LC MBL)	NCT06416267	Monoclonal B-Ce... Chronic Lymphoc... Infections Cancers Cardiovascular ... Alzheimer Disea... Dementia Autoimmune Dise... Parkinson Disea...		40 Years -	University of Haifa
The Communication of Genetic Risk to Adolescent Daughters of Women With Breast Cancer	NCT00588705	Breast Cancer Counseling	focus group & q...	12 Years - 20 Years	Memorial Sloan Kettering Cancer Center
Family Health History in Diverse Care Settings (FHH)	NCT01956773	Diabetes Heart Disease Cancer	MeTree	18 Years -	Duke University
The Communication of Genetic Risk to Adolescent Daughters of Women With Breast Cancer	NCT00588705	Breast Cancer Counseling	focus group & q...	12 Years - 20 Years	Memorial Sloan Kettering Cancer Center
Personalised Risk-based Breast Cancer Prevention and Screening	NCT03989258	Breast Cancer	Mammography out...	25 Years -	Tartu University Hospital
Direct Information to At-risk Relatives	NCT04197856	Familial Breast... Familial Colore... Hereditary Brea... Hereditary Brea... Lynch Syndrome	Standard care e... Offer of health...	18 Years -	Umeå University
Risk and Clinical Consequences of Low Count Monoclonal B-cell Lymphocytosis (LC MBL)	NCT06416267	Monoclonal B-Ce... Chronic Lymphoc... Infections Cancers Cardiovascular ... Alzheimer Disea... Dementia Autoimmune Dise... Parkinson Disea...		40 Years -	University of Haifa

Spots Global Cancer Trial Database for genetic risk

Every month we try and update this database with for genetic risk cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.