Novel Molecular Targets for Ductal Carcinoma In Situ (DCIS)

NCT03148015 | Completed

• 1 other identifier: 16-03-EX-0064
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Duration of Study, estimated 2 years

Secondary Outcomes (2)

• Biomarkers

  Duration of Study, estimated 2 years

• Histopathologic/Molecular Characteristics by lesion type

  Duration of Study, estimated 2 years

Study Arms (3)

ADH/LCIS

Atypical Ductal Hyperplasia or Lobular carcinoma in situ with DCIS

Other: Biomarkers

DCIS

Pure Ductal Carcinoma in Situ

Other: Biomarkers

Invasive

invasive ductal carcinoma with DCIS

Other: Biomarkers

Interventions

Biomarkers OTHER

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.

ADH/LCIS; DCIS; Invasive

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Sentara Norfolk General Hospital: lead
• George Mason University: collaborator
• Dorothy G. Hoefer Foundation: collaborator

Study Sites (1)

Sentara Surgery Specialists and Dorothy G Hoefer Comprehensive Breast Center

Newport News, Virginia, 23606, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biopsy or surgical tissue specimen slides.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Biomarkers

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biological Factors

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 10, 2017
• Study Start: October 1, 2016
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: May 27, 2022

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)