Novel Molecular Targets for Ductal Carcinoma In Situ (DCIS)

May 25, 2022 updated by: Sentara Norfolk General Hospital

This project is an immunohistochemical study of archived patient breast tissue, specifically pre-invasive lesion specimens. The purpose is the discovery of novel molecular markers of pre-invasive breast lesions. These novel markers, once validated in this study, can serve as targets for individualized prevention therapy, neoadjuvant therapy for ductal carcinoma in situ (DCIS), or predictors of lesion aggressiveness. We have discovered two novel classes of DCIS molecular pathways required for the survival of DCIS neoplastic cells that will serve as the basis for the candidate molecules to be evaluated in this proposed study. The first class of DCIS molecular markers is autophagy, a cell survival mechanism that we discovered to be highly augmented in the hypoxic and nutrient deprived intraductal neoplastic cells of human DCIS (1-4). The second class of biomarker is calcium efflux that is mediated in breast cells by the calcium export pump Plasma Membrane Calcium ATPase (PMCA2) (5, 6). During normal lactation, breast epithelium pumps large concentrations of calcium into milk. In neoplastic lesions, calcium is exported by PMCA2 as a cell survival mechanism, since cells under metabolic stress accumulate calcium to a toxic level. Calcium export in DCIS may also contribute to intraductal calcifications, a hallmark of high grade DCIS and the most common marker of DCIS on mammography (7).

Sentara cares for hundreds of patients per year who are diagnosed with breast pre-invasive lesions, including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS). Sentara treats 25% of the women with breast cancer in Virginia. Coupled with information from the Sentara Cancer Registry, Dr. Hoefer or a research team member will identify eligible patients with ADH, DCIS, and/or LCIS at the time of the core biopsy diagnosis, surgical therapy, and/or upon lesion recurrence. After receiving written informed consent from the eligible patients, Sentara Pathology will retrieve the corresponding tissue blocks. The recut tissue sections will be processed at George Mason University, Center for Applied Proteomics and Molecular Medicine for markers relevant to calcium signaling, Vitamin D response, proliferation, autophagy and inflammation. Combined with the translational research expertise/technology in the Center for Applied Proteomics and Molecular Medicine at George Mason University, Sentara's diverse patient cohort provides an opportunity to address the most fundamental unanswered questions surrounding the etiology, progression, and therapy of pre-invasive breast lesions.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Sentara Healthcare is a progressive and integrated healthcare organization that cares for hundreds of patients per year who are diagnosed with breast cancer and pre-invasive lesions, including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS). Sentara Healthcare maintains a Cancer Registry which includes complete clinical information and disposition information of tissue blocks collected at the time of the core biopsy diagnosis, the surgical therapy, and upon lesion recurrence. Combined with the translational research expertise/technology in the Center for Applied Proteomics and Molecular Medicine (CAPMM) at George Mason University (GMU), the Sentara Healthcare extensive patient cohort provides an opportunity to address the most fundamental unanswered questions surrounding over-treatment and under-treatment of pre-invasive breast lesions:

  1. Does the histopathologic/molecular character of the carcinoma in situ, the immune infiltrate, and/or the stroma, correlate with the type of lesion (ADH, DCIS or LCIS), the grade of the lesion, or the presence of later recurrence?
  2. Does the level of autophagy within the lesion duct, or the level of PMCA2, of the pre-invasive lesion, correlate with lesion grade, the level of apoptosis, or the presence of later recurrence?
  3. Does the level of Vitamin D receptor correlate with the level of PMCA2?

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Newport News, Virginia, United States, 23606
        • Sentara Surgery Specialists and Dorothy G Hoefer Comprehensive Breast Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Female patients aged 18 or older who have had a breast biopsy and or surgery with breast tissue available. Patient must be diagnosed with ADH, DCIS, LCIS or invasive ductal cancer.

Description

Inclusion Criteria:

  • Patients must be female, at least 18 years of age.
  • Patients or their legally authorized representative must have signed and dated an informed consent form
  • Patients must have at minimum, adequate samples of breast tissue available for use in this study.
  • Patients with a tissue diagnosis of low, intermediate or high grade ductal carcinoma in situ or ductal carcinoma in situ with microinvasion.
  • Patients with a diagnosis of atypical ductal hyperplasia, lobular cancer in situ or any preinvasive breast lesion.
  • Patients with ductal carcinoma in situ undergoing either lumpectomy and radiation or mastectomy.
  • Patients with a diagnosis of invasive ductal cancer.

Exclusion Criteria:

  • Male.
  • Patients under the age of 18 or over the age of 89.
  • Patient desires not to participate in the study.
  • Inability to consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ADH/LCIS
Atypical Ductal Hyperplasia or Lobular carcinoma in situ with DCIS
Other: Biomarkers
Evaluate the intracellular and intraluminal distribution of autophagy and calcium efflux markers in each breast lesion in comparison to the HER2, proliferation (Ki-67, PCNA), p53, inflammatory, and apoptotic (Annexin-1) markers in the same patient. Determine the qualitative amount and localization of PMCA2 and Vitamin D Receptor in each breast lesion with intraductal calcium spicules compared to lesions without microcalcifications.
DCIS
Pure Ductal Carcinoma in Situ
Other: Biomarkers
Evaluate the intracellular and intraluminal distribution of autophagy and calcium efflux markers in each breast lesion in comparison to the HER2, proliferation (Ki-67, PCNA), p53, inflammatory, and apoptotic (Annexin-1) markers in the same patient. Determine the qualitative amount and localization of PMCA2 and Vitamin D Receptor in each breast lesion with intraductal calcium spicules compared to lesions without microcalcifications.
Invasive
invasive ductal carcinoma with DCIS
Other: Biomarkers
Evaluate the intracellular and intraluminal distribution of autophagy and calcium efflux markers in each breast lesion in comparison to the HER2, proliferation (Ki-67, PCNA), p53, inflammatory, and apoptotic (Annexin-1) markers in the same patient. Determine the qualitative amount and localization of PMCA2 and Vitamin D Receptor in each breast lesion with intraductal calcium spicules compared to lesions without microcalcifications.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Molecular and Histopathologic Characteristics
Time Frame: Duration of Study, estimated 2 years
Demonstrate the concomitant activation of autophagy and calcium efflux in pre-invasive breast lesions. Compare the molecular and histopathologic characteristics of the breast DCIS/invasive lesion to the lesion microenvironment.
Duration of Study, estimated 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Biomarkers
Time Frame: Duration of Study, estimated 2 years
Identify and characterize biomarkers in the DCIS breast lesion and invasive that correlate with autophagy, calcium signaling and inflammation.
Duration of Study, estimated 2 years
Histopathologic/Molecular Characteristics by lesion type
Time Frame: Duration of Study, estimated 2 years
Establish the histopathologic/molecular character of the stroma, the pre-invasive lesion, and correlate with the type of lesion (ADH, DCIS or LCIS), the grade of the lesion, or the presence of invasive carcinoma.
Duration of Study, estimated 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sentara Norfolk General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
George Mason University
Dorothy G. Hoefer Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 1, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 10, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 27, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16-03-EX-0064

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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