Breast CancerNCT03148015
Novel Molecular Targets for Ductal Carcinoma In Situ (DCIS)
An observational study of Breast Cancer, run by Sentara Norfolk General Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Biomarkers
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2016to 31 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Male.
- Patients under the age of 18 or over the age of 89.
- Patient desires not to participate in the study.
- Inability to consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sentara Surgery Specialists and Dorothy G Hoefer Comprehensive Breast Center
Newport News, Virginia, 23606
About this study
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.
Read the 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:
- 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?
- 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?
- Does the level of Vitamin D receptor correlate with the level of PMCA2?
- Conditions
- Breast Cancer
- Being tested
- Biomarkers
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiomarkersOther
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.
| Study group | Role | What they receive |
|---|---|---|
| ADH/LCIS | Atypical Ductal Hyperplasia or Lobular carcinoma in situ with DCIS Receives: Other: Biomarkers | |
| DCIS | Pure Ductal Carcinoma in Situ Receives: Other: Biomarkers | |
| Invasive | invasive ductal carcinoma with DCIS Receives: Other: Biomarkers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular and Histopathologic Characteristics
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.
Measured: Duration of Study, estimated 2 years
Secondary outcomes (2)
Biomarkers
Identify and characterize biomarkers in the DCIS breast lesion and invasive that correlate with autophagy, calcium signaling and inflammation.
Measured: Duration of Study, estimated 2 years
Histopathologic/Molecular Characteristics by lesion type
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.
Measured: Duration of Study, estimated 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2017
- Study start1 Oct 2016
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sentara Norfolk General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- George Mason University, Dorothy G. Hoefer Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03148015
- Sponsor's protocol ID
- 16-03-EX-0064
- Status last verified
- Sep 2021
- First submitted
- 1 May 2017
- Last updated
- 27 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Molecular Targets for Ductal Carcinoma In Situ (DCIS)
- ClinicalTrials.gov ID
- NCT03148015
- Acronym / sponsor ID
- 16-03-EX-0064
- Conditions
- Breast Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Sentara Norfolk General HospitalUniversity, hospital or other
- Collaborators
- George Mason University, Dorothy G. Hoefer Foundation
- Study start
- 1 Oct 2016 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 10 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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?
- 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?
- Does the level of Vitamin D receptor correlate with the level of PMCA2?
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ADH/LCIS | – | Other: BiomarkersAtypical Ductal Hyperplasia or Lobular carcinoma in situ with DCIS |
| DCIS | – | Other: BiomarkersPure Ductal Carcinoma in Situ |
| Invasive | – | Other: Biomarkersinvasive ductal carcinoma with DCIS |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (4 listed)
- Male.
- Patients under the age of 18 or over the age of 89.
- Patient desires not to participate in the study.
- Inability to consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiomarkersEvaluate 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. | Other | ADH/LCIS, DCIS, Invasive |
Primary outcome
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.
2 secondary outcomes
Biomarkers
Time frame: Duration of Study, estimated 2 years
Histopathologic/Molecular Characteristics by lesion type
Time frame: Duration of Study, estimated 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by Sentara Norfolk General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Molecular and Histopathologic Characteristics (time frame: Duration of Study, estimated 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2022.