Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Hyperplasia

Breast Diseases

Skin Diseases

Bruce Kimler, Ph.D.

Carol J Fabian, MD

Bruce Kimler, PhD

The overall goal of this project is to develop an integrative system of breast cancer risk assessment based on epidemiologic and biologic risk variables, as well as to develop or refine risk biomarkers which may be useful in predicting and monitoring response to prevention interventions.

1. To correlate established risk biomarkers such as cytomorphology obtained from random periareolar fine needle aspiration ( RPFNA), mammographic breast density, serum bioavailable estradiol and IGF-1/IGFBP-3 with each other and with 5-10 year Gail risk estimates. Where available, and with appropriate safe guards to maintain status for breast cancer susceptibility genes may be included.
2. To determine the relative predictive value of established risk biomarkers for the development of DCIS and/or invasive cancer.
3. To evaluate potential new breast tissue-based biomarkers including Ki-67, PCNA, ER, COX-2, aromatase, methylation of key tumor suppressor genes (i.e., RAR, p16, etc), proteomic patterns in RPFNA and nipple aspirate fluid (NAF), as well as NAF hormone levels, and correlate them with other risk biomarkers listed in 1.
4. To determine the prevalence of polymorphisms of a panel of genes important in hormone and xenobiotic metabolism as well as DNA repair and correlate these polymorphisms with established risk biomarkers listed in 1, as well as with development of DCIS and invasive cancer.
5. To maintain contact with this initially identified cohort of high risk women, acquire demographic data, biologic specimens and data and follow them prospectively for the development.

Protocol for Women at Increased Risk of Developing Breast Cancer

High Risk Breast Clinic: Protocol for Women at Increased Risk for Developing Breast Cancer

development of algorithm for predicting risk for developing breast cancer based on random sampling of benign breast tissue.

Carol Fabian, MD

Professor, Director Breast Cancer Prevention Unit

Participants receiving the intervention will complete a pretest, watch the decision aid video, and complete posttest via tablet computer facilitated by Patient Navigators.

Participants receiving the control will complete pretest, review a genetic counseling brochure with the Patient Navigators, and complete posttest via tablet computer facilitated by a Patient Navigator.

Decision aid video

Genetic counseling informational brochure

Kent Hoskins, MD

Erica Seltzer, DrPH

Vida Henerson, PhD

Vida Henderson, PhD

Erica I Seltzer, DrPH

In the United States, carriers of hereditary genetic mutations have up to an 85% risk of developing breast cancer compared to 12% in the general population. Overall uptake of genetic services is generally low, particularly among high-risk African American (AA) women, who carry a disproportionate burden of breast cancer mortality. Further, although testing close relatives of individuals who test positive for a pathogenic variant might curtail breast cancer disparities attributable to hereditary risk, it is unclear how counseled or tested individuals influence their social and familial networks. Using a randomized control trial design, the objective of this research project is to test the effectiveness of a culturally targeted video, previously developed by our research team, on promoting genetic counseling attendance among AA women determined to be at high risk for breast cancer through cancer genetic risk assessment in a clinical setting. This study will also test how psychosocial factors (knowledge, intrinsic motivation, risk perception, and distress) impact the relationships between intervention exposures (video versus brochure) and compare the impact of intervention exposures on diffusion of knowledge about genetic counseling through social network analysis.

Study Design. The investigator will conduct a randomized control trial single-blind control trial to test the effectiveness of a culturally targeted decision aid video to promote genetic counseling among African American determined to be high risk for breast cancer through cancer genetic risk assessment. Eligible patients will be randomly assigned to receive information about genetic counseling using a culturally targeted decision aid video (treatment group) or a brochure (control).

Research Protocol. As part of standard of care, patients will complete a cancer genetic risk assessment (CGRA) as part of intake on a tablet computer provided by the front desk clinic staff. CGRA results will be uploaded to the EMR, printed and given to a patient navigator. The patient navigator will approach patients, give them a recruitment flyer, information about the study, screen patients and obtain informed consent for women who choose to participate in the study. Based on computer-generated randomization (equal numbers in each arm), patients will be randomized to one of two groups to receive: 1) pretest, view decision aid video, and posttest or 2) pretest, genetic counseling brochure, and posttest. Both arms will be facilitated by patient navigators. Upon completion of posttest, patient navigators will ask women if they would like to make an appointment for genetic counseling, contact the provider for the order if not already in the EMR, make genetic counseling appointments for women who choose to attend, and monitor and collect follow-up data. All enrolled participants will receive a phone call at 4 weeks post-intervention to (a) verify counseling attendance through self-report and EMR extraction if applicable; (b) ask whether the patient was referred to genetic testing after her genetic counseling if applicable; and (c) ask whether other family members were referred to genetic services if applicable and (d) determine who in their social networks, if anyone, the participant told about genetic counseling, and if so, how this information was shared.

Computer-generated randomization (equal numbers in each arm), patients will be randomized to one of two arms:

1. Decision aid video
2. Genetic counseling informational brochure

Promoting Genetic Counseling Among African American Women With a Family History of Breast Cancer

Compare the effects of intervention vs. control arm on genetic counseling attendance among African American women recommended for genetic counseling through cancer genetic risk assessment.

Assessed via EMR and survey at follow-up.

2-item (Did patient complete genetic counseling appointment? A) Self-report and B) EMR)

1 items assessing familial referral to genetic counseling or testing

5-item agreement likert scale to assess usability, satisfaction, decisional conflict (e.g., I felt I could relate to what the actors were saying?)

Assessed via survey at immediate posttest

Items to assess changes in knowledge about genetic counseling for breast cancer risk between pre and post intervention; (e.g., A purpose of genetic counseling is to help people understand their options for genetic testing.)

Relevant items from published instrument (Maio) and Facing Our Risk of Cancer Empowerment (FORCE) brochure (control arm brochure) adapted for genetic counseling for breast cancer.

Assessed via survey at pretest and posttest.

Items to assess patient worry/anxiety related to genetic counseling and breast cancer risk; (e.g., How often have you thought about your chances of getting cancer?)

7-item Cancer Worry Scale

Assessed via survey at pretest and posttest.

Items to assess motivation for genetic counseling attendance (e.g., The reason I would attend genetic counseling is because I feel that I want to take responsibility for my own health.)

15-item Treatment Self-Regulation Questionnaire and 4-item Self-Efficacy Scale

Assessed via survey at pretest and posttest.

Items to assess perception of risk related to getting breast cancer (In your opinion, compared to other women your age, what are your chances of getting breast cancer?)

1-item question obtained from published instrument.

Assessed via survey at pretest and posttest.

Items to assess sharing of knowledge among social and familial networks about genetic counseling. Diffusion of knowledge will be assessed by collecting data on social network size, composition, density, and information sharing related to genetic counseling and risks.

Relevant social network assessment items-General Social Survey.

Examples:

* Name generator: (From time to time, most people discuss important matters with other people. Looking back over the past month, who are the people with whom you discussed genetic counseling or genetic risks?
* Name interpreter: (e.g., What is relationship between you and X?)

Assessed at 4 week follow-up

National Cancer Institute (NCI)

University of Illinois at Chicago

Principal Investigator

Fibrocystic Breast Disease

Amy C Whiffen, MPH

Lisa Held, BA

Rhonda Theodore

Kathie-Ann Joseph, MD, MPH

The purpose of this study is to increase understanding of women who are at high risk for developing breast cancer. Data from this group will be collected and entered into a registry. This registry serves as a clinical database to support research in prevention, early detection and treatment of breast cancer.

This is a longitudinal cohort study that collects data of eligible women at risk for developing breast cancer. Patient information will be entered into a secured computerized database that is used for research on the prevention, early detection and treatment of breast cancer.

Women At Risk: The High Risk Breast Cancer Program

Women At Risk

New York Presbyterian Hospital

Amy Whiffen

Routine scheduled MRI with contrast performed on women at high risk of developing breast cancer. One day after routine MRI, short breast MRI (SBMRI) with contrast performed. After SBMRI, participant completes a questionnaire about their comfort level and experience of the research scan.

One day after routine MRI, short breast MRI (SBMRI) with contrast performed. Scan will take about 10 minutes to complete.

Short Breast MRI (SBMRI)

After SBMRI, participant completes a questionnaire about their comfort level and experience of the research scan. It should take about 10 minutes to complete the questionnaire.

Questionnaire

Marion E. Scoggins, MD

The goal of this clinical research study is to test if a short breast MRI scan (about 10 minutes) can be used for breast cancer screening in high risk people and to learn if it is as effective as a routine breast MRI scan (30-60 minutes).

If you agree to take part in this study, you will have the short breast MRI scan (the scan for research purposes) with contrast on a different day than your scheduled routine MRI screening scan with contrast. You will have your routine scan the first day and the research scan at least 1 day after. The research scan will take about 10 minutes to complete.

After your short breast MRI scan is completed, you will complete a questionnaire about your comfort level and experience of the research scan. It should take about 10 minutes to complete the questionnaire.

This is an investigational study. The short breast MRI is considered investigational.

Up to 200 participants will be enrolled in this study. All will be enrolled at MD Anderson.

Feasibility of Short Breast MRI (SBMRI) for Screening Patients at High Risk for Breast Cancer

Radiologists blinded to patient outcome review images from each study independently and rate the possibility of breast cancer using BI-RADS score. BIRADS 0, 3,4, 5 considered positive, BIRADS 1 and 2 considered negative results for the analysis. Each reader's score for a given case assessed both independently and on a separate session, as consensus.

GE Healthcare

M.D. Anderson Cancer Center

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Celecoxib

Cyclooxygenase 2 Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Oral Celecoxib 400 mg twice daily for 12 months

Matched blinded placebo twice daily for 12 months

celecoxib

placebo

To assess the effects of twelve months of celecoxib administration by evaluating breast tissue needle aspirations, to determine if cell growth can be slowed.

A blind randomized study of celecoxib in women at high risk of developing breast cancer. Subjects are to take twelve months of drug/placebo. At baseline and after twelve months subjects will have a random periareolar fine needle breast aspiration that will be assessed for epithelial cell growth and other markers of risk. Baseline and twelve month serum samples will also be assessed for hormones and growth factors which may be associated with breast cancer risk. Mammograms at baseline and twelve months will also be assessed for breast density changes.

A Double-blinded Phase II Study of the Expression of Ki-67/MIB-1 in Women With Hyperplasia of the Breast Randomized to Receive Daily Celecoxib 400 mg BID or Placebo

Immunocytochemical staining of breast epithelial cells. Positive cells reflect proliferative activity.

The percent of mammographic breast area that is considered to be at increased density. Evaluated using the semi-automated computer program Cumulus.

Susan G. Komen Breast Cancer Foundation

Randomized to receive celecoxib daily for 12 months

Randomized to receive palcebo daily for 12 months

Placebo

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Carol Fabian

Randomized to receive placebo daily for 12 months

Change in Percent of Breast Epithelial Cells Staining Positive for Ki-67

Difference between groups, two-sided. Endpoint not specifically powered for effect.

Oral Celecoxib 400 mg twice daily for 12 months

celecoxib: Celecoxib 400 mg BID

Matched blinded placebo twice daily for 12 months

placebo: placebo

Subjects completing 12 months, with baseline and 12 month mammograms suitable for density analysis, such that a change in density over time can be computed

Mammographic Breast Density

Serum Estradiol Concentration

Serum Sex Hormone Binding Globulin (SHBG) Concentration

Molecular Ratio of Serum Concentration of IGF-1 to IGFBP3

Overall Study

Antineoplastic Agents

Hormones

Letrozole

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Oral Letrozole 2.5 mg daily for six months

letrozole

A pilot study to assess the effects of six months of letrozole on breast tissue risk markers in postmenopausal women on hormone replacement therapy at high risk of developing breast cancer.

A pilot study of letrozole in postmenopausal women on hormone replacement therapy at high risk of developing breast cancer. Subjects will have hyperplasia with atypia (or borderline Epithelial Hyperplasia/Atypical Hyperplasia) and evidence of Estrogen Receptor expression by random periareolar fine needle aspiration and baseline serum estradiol levels less than or equal to 150 pg/ml. The feasibility of performing RT-qPCR on breast specimens for aromatase expression will also be done at baseline.

Study of the Effect of Letrozole on Breast Biomarkers of High Risk Postmenopausal Women Receiving Hormone Replacement Therapy

Proliferation assessment by immunocytochemistry using Ki-67. Expressed as percent of cells staining positive for Ki-67.

Novartis

Carol J. Fabian, M.D.

All subjects completed study and were used for analysis

Change in Proliferation of Breast Epithelial Cells Obtained by Random Periareolar Fine Needle Aspiration.

Menopause

To examine nipple aspirate fluid for secretions that may be identified as a high risk indicator for development of breast cancer, and compare those to serum analysis.

To examine nipple aspirate fluid analysis in lactating women for local concentration of estrogen, prolactin, glucocorticoids, insulin, parity, prior lactation and age. NAF secretors have been reported to have modest increase in breast cancer risk compared to non-secretors . Estrogen levels have been found to be markedly higher in NAF samples than in the serum collected from the same women. Estradiol and estrone concentrations in premenopausal women are 10x and 20x greater in NAF samples than in serum and 50x and 35x greater in post-menopausal women not on HRT. It has been suggested that the disparity between serum and NAF levels may be due to local estrogen production via aromatase and sulfatase.

Protocol for Postmenopausal Women at Increased Risk of Developing Breast Cancer

Study of Manual Nipple Fluid Aspiration IN Post-Menopausal Women

Bone Density Conservation Agents

Micronutrients

Vitamins

Vitamin D

Cholecalciferol

Trace Elements

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

oral capsules, 10,000 IU per week for 6 months

vitamin D3

The overall goal of this project is to determine if high dose vitamin D3 given to premenopausal women at high risk for development of breast cancer, who initially have insufficient levels of 25-hydroxy vitamin D (\<30 ng/ml), will raise 25(OH)D levels above 50 ng/ml. If so, will certain risk biomarkers for development of breast cancer be reliably and favorably modulated?

Protocol Objectives:

To determine if high dose vitamin D3 given to premenopausal women who initially have insufficient levels of 25-hydroxy vitamin D (\<30 ng/ml) will raise 25(OH)D levels above the 50 ng/ml level considered to be required for breast health. If so, will certain risk biomarkers for development of breast cancer be reliably and favorably modulated? The primary endpoint will be a decrease in mammographic breast density (percent area considered at increased density). Change in proliferation (a decrease as assessed by Ki-67) will also be examined. Modulate of expression of genes important in breast cancer risk or reflective of vitamin D's mechanism of action will be studied using quantitative real time polymerase chain reaction (qRT-PCR).

Study Design:

The study is a single-arm open label clinical trial. Women who are high risk for development of breast cancer on the basis of family or personal history will undergo random periareolar fine needle aspiration (RPFNA) to acquire breast cells for assessment of gene expression by qRT-PCR. Women with mammographic density \>10% will be eligible for enrollment. All subjects will receive high dose vitamin D3 (3 capsules of 10,000 IU of vitamin D3 every week for 6-8 months). At that time, a repeat RPFNA and mammogram will be performed. Measurement of serum levels of 25(OH)D will be performed at baseline, 3 months, and 6 months.

Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D

Change in the percent of the breast area that is considered to be at higher density on mammogram.

Change in percent of cells expressing staining for Ki-67 antibody in breast epithelial cell specimens acquird by Random Periareolar Fine Needle Aspiration.

Assessment of 25(OH)D levels as a measure of circulating vitamin D.

BTR Group

Group/Cohort Label vitamin D3

vitamin D3: oral capsules, 10,000 IU per week for 6 months

High Dose Vitamin D3 (10,000 IU Weekly)

Female

Sex/Gender, Customized

Race (NIH/OMB)

Ethnicity (NIH/OMB)

Gail model is an algorithm to calculate a predicted probability of developing breast cancer within the next 5 years.

Gail Risk 5-year Probability of Cancer Development

Single arm pilot trial so all comparisons are within subject for change over the course of the study.

Bruce F. Kimler, Ph.D.

Change in Mammographic Breast Density Over Course of Study

Change in Proliferation (as Assessed by Ki-67) Examined in Breast Epithelial Cells.

OH Vitamin D Levels in Serum

Web-Based Decision Support

Background:

* Chemoprevention is the use of preventive medications to reduce the risk of breast cancer for women who are at a high risk of developing the disease. Although the treatment has shown effectiveness in preventing cancer development, chemoprevention is notably underutilized even by women who are at a high risk of developing breast cancer.
* Researchers are interested in determining if better decision support mechanisms, such as interactive Web sites, can help to overcome some of the barriers to chemoprevention.

Objectives:

- To develop and test a prototype Web-based module that will provide decision support to women who are considering chemoprevention for breast cancer.

Eligibility:

* Women 35 years of age and older who are at high risk for breast cancer and whose doctor has recommended chemoprevention (either Tamoxifen or Raloxifene), and who have no other history of cancer (apart from non-melanoma skin cancer or precancerous cervical lesions).
* Participants must have a working e-mail address and access to a computer with internet access and a telephone.

Design:

* Participants who are considering chemoprevention will be randomized to a Web-based decision support module or standard care online information resources.
* Participation lasts two months and involves using the online resources provided and filling out questionnaires two times during the study (at the beginning and the end).

The first time will be at the begin of the study.

* No medical treatments are offered as a part of this study

BACKGROUND:

* Breast cancer chemoprevention has been notably underutilized.
* Barriers to integrating breast cancer risk reducing measures include: lack of time, low priority of risk reduction in comparison to treatment, the need to personalize risks and benefits of chemoprevention, and the need for resources/information necessary for women to make informed decisions.
* Access to quality decision support resources to facilitate making informed, preference-sensitive decisions about chemoprevention may provide a mechanism to overcome some of the current barriers to chemoprevention utilization.

OBJECTIVES:

* Develop and refine a web-based patient decision support module for high-risk women making a decision about breast cancer chemoprevention.
* Conduct a randomized study of TACHD decision support versus standard care online information support to evaluate the impact of the chemoprevention module of the TACHD decision support intervention.

ELIGIBILITY:

* Women with no history of cancer other than cervical carcinoma in situ or non-melanoma skin cancer
* High risk for breast cancer based on at least one of the following:

  * Gail score \> 1.67
  * History of atypical hyperplasia (either ductal or lobular)
  * History of lobular carcinoma in situ
  * Documentation of a deleterious BRCA1 or BRCA2 mutation
* Considering a decision about chemoprevention with tamoxifen or raloxifene
* Access to an IBM-compatible or MacIntosh personal computer with broadband Internet access
* Access to an email account
* Access to a telephone
* Aged 35 or older
* Able to communicate in English verbally and in writing

DESIGN:

* The project will be guided by the Cognitive-Social Health Information Processing (CSHIP) model overall, and incorporate the Ottawa Decision Support. Framework (ODSF) in one consistent decision support process.
* Testing of the chemoprevention decision support module will be conducted in a two-group pre- post-test experimental design with 64 at-risk women identified through Fox Chase Risk Assessment Programs and the NCI Clinical Cancer Genetics Program (CCGP) at the National Naval Medical Center (NNMC).
* A process evaluation analysis will assess participants' experiences using TACHD.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Protocol for Women at Increased Risk of Developing Breast Cancer	NCT00291096	Breast Cancer		30 Years - 65 Years	University of Kansas Medical Center
Protocol for Women at Increased Risk of Developing Breast Cancer	NCT00291096	Breast Cancer		30 Years - 65 Years	University of Kansas Medical Center
Promoting Genetic Counseling Among African American Women With a Family History of Breast Cancer	NCT04378751	High Risk for B...	Decision aid vi... Genetic counsel...	25 Years -	University of Illinois at Chicago
Women At Risk: The High Risk Breast Cancer Program	NCT01034891	Breast Cancer		18 Years -	New York Presbyterian Hospital
Feasibility of Short Breast MRI (SBMRI) for Screening Patients at High Risk for Breast Cancer	NCT02590458	Breast Cancer	Short Breast MR... Questionnaire	18 Years -	M.D. Anderson Cancer Center
Protocol for Women at Increased Risk of Developing Breast Cancer	NCT00291694	Breast Cancer	celecoxib placebo	18 Years -	University of Kansas Medical Center
Protocol for Women at Increased Risk of Developing Breast Cancer	NCT00291135	Breast Cancer	letrozole	18 Years -	University of Kansas Medical Center
Protocol for Postmenopausal Women at Increased Risk of Developing Breast Cancer	NCT00291083	Breast Cancer		18 Years -	University of Kansas Medical Center
Modulation of Breast Cancer Risk Biomarkers by High Dose Vitamin D	NCT01166763	Breast Cancer	vitamin D3	- 55 Years	University of Kansas Medical Center
Feasibility of Short Breast MRI (SBMRI) for Screening Patients at High Risk for Breast Cancer	NCT02590458	Breast Cancer	Short Breast MR... Questionnaire	18 Years -	M.D. Anderson Cancer Center
Facilitating Web-based Patient Decision Support: Decision About Medication to Lower Breast Cancer Risk	NCT00906321	High Risk for B... Risk Reduction ...	Web-Based Decis...	35 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Protocol for Women at Increased Risk of Developing Breast Cancer	NCT00291135	Breast Cancer	letrozole	18 Years -	University of Kansas Medical Center

Spots Global Cancer Trial Database for high risk for breast cancer