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Last Updated: 10/10/18

Dana-Farber/Harvard SPORE in Breast Cancer

Principal Investigator:
Eric P. Winer, MD, Principal Investigator (2011-present)
J. Dirk Iglehart, MD, former Principal Investigator (2000-2010)

PRINCIPAL INVESTIGATOR CONTACT INFORMATION

Eric Winer, MD
Chief Clinical Strategy Officer
Dana-Farber Cancer Institute
Department of Medical Oncology
Division of Women’s Cancers
450 Brookline Avenue, Boston, MA 02215
Tel: (617) 632-2261
Fax: (617) 632-1930
Email: ewiner@partners.org

OVERVIEW

The Dana-Farber/Harvard SPORE in Breast Cancer (Breast SPORE) features five research projects, five cores, a developmental project program, a career development program and several NCI-Avon Progress for Patients supplement awards. The Breast SPORE is an integral component of the Dana-Farber/Harvard Cancer Center (DF/HCC) and represents significant translational research collaboration in breast cancer.

The Projects in the Breast SPORE fall into two broad categories:

  • Projects starting with treatments:
    • BRCA1-associated and basal-like breast cancer
    • Combination therapy for HER2-positive breast cancer
    • Co-activators of the estrogen receptor and resistance to endocrine therapy
  • Projects starting with tissues:
    • The influence of tumor-stromal cell interactions
    • Discovering susceptibility factors by interactions between functional screening and population studies

The Cores deliver the benefits of efficiencies to the Projects, as well as to the other Cores, by centralizing these specific functions and responsibilities; it allows the Breast SPORE to effectively leverage its resources.

  • Tissue and Pathology
  • Clinical Studies
  • Cohort Studies and Databases
  • Biostatistics and Bioinformatics
  • Communication, Planning and Administration

PROJECTS:

BRCA1-ASSOCIATED AND BASAL-LIKE BREAST CANCER

  • Aim 1: Compare the molecular phenotypes of BLC and BRCA1-mutant breast cancers.
  • Aim 2: Identify specific functional defects in DNA repair in BLC using DNA repair assays in viable tumor cells obtained from clinical samples.
  • Aim 3: Access the response of a cohort of ER (-), PR (-), Her2 (-) breast cancers to cis-platinum in a phase II neo-adjuvant clinical trial and determine if results of informative assays developed above correlate with clinical response.

COMBINATION THERAPY FOR HER2-POSITIVE BREAST CANCER

  • Aim 1: Evaluate biomarkers of sensitivity and resistance to HER2-directed therapy
  • Aim 2: Evaluate combinations of trastuzumab and signaling inhibitors
  • Aim 3: Conduct unbiased screens for targets whose inhibition sensitizes to HER2-directed treatments

CO-ACTIVATORS OF THE ESTROGEN RECEPTOR AND RESISTANCE TO ENDOCRINE THERAPY

  • Aim 1: Determine the function of AIB1 and other coregulators in altering ER activity in breast cancer cells in culture under low estrogen conditions.
  • Aim 2: Study the role of AIB1 and its interaction with growth factor signaling pathways in mediating the response to AIs in a transgenic mouse model.
  • Aim 3: Perform brief exposure pre-surgical trials of AIs in postmenopausal women with newly diagnosed ER+ breast cancer.

THE INFLUENCE OF TUMOR-STROMAL INTERACTIONS

  • Aim 1: To determine if stromal cells from uninvolved breast tissue from patients with breast cancer are more conducive to cancer development than stromal cells of women without cancer.
  • Aim 2: To identify gene expression signatures of stromal cells associated with cancer, stromal cells from uninvolved breast tissue from patients with breast cancer, and stromal cells from breasts without cancer.
  • Aim 3: To determine in human breast tissue samples if there is an association between stromal markers and epithelial lesions associated with increased breast cancer risk, and to determine if there are stromal markers that can be used as independent risk indicators.

DISCOVERING SUSCEPTIBILITY FACTORS BY INTERACTIONS BETWEEN FUNCTIONAL SCREENING AND POPULATION STUDIES

  • Aim 1: Examine if common genetic variants of EGF-R, ERBB2, CSF-1R and IGF-1R are associated with increased risk of breast cancer.
  • Aim 2: Examine if rare variants of EGF-R, ERBB2, CSF-1R, and IGF-1R display distinct functional activities and if so, whether they are associated with familial breast cancer.
  • Aim 3: Protein expression status in tissue microarrays of breast cancer tumors.
  • Aim 4: Plasma levels of protein ligands are associated with subsequent breast cancer risk.

CORES:

TISSUE AND PATHOLOGY

The SPORE Tissue and Pathology Core maintains a tissue repository that includes a frozen specimen bank that collects fresh breast tumor and matched normal tissues, normal breast tissues from reduction mammoplasties, and metastatic breast cancer specimens. These samples are provided to investigators as fresh tissue for cell sorting or tissue culture experiments, as frozen tissue or frozen sections, or as extracted DNA, RNA or protein. The processing and annotation of these specimens is a key role of the SPORE tissue repository. Currently the SPORE has more than 200 specimens with HER2-positive breast cancer and an equal number of specimens with triple-negative cancer in paraffin block tissue microarrays. These samples have matched frozen tissue, pathology annotation, clinical outcome annotation, and gene expression array profile data while a portion of these samples have SNP array genomic profile data. In addition, the repository collects, stores, and processes breast core biopsy samples, and surgical samples, in conjunction with SPORE and DFCI therapeutic trials.

This Core maintains the SPORE Core Blood Repository (SCBR) to collect, process, annotate, store and distribute blood-derived samples from consented breast cancer patients seen at our SPORE-affiliated institutions. Whole blood, plasma, serum and buffy coats (lymphocytes) are the various components currently stored in the bank. A bar-coding system is employed to interface with our STIP (Specimen Tracking and Inventory Program) database system.

CLINICAL STUDIES

This Core facilitates all SPORE-related clinical research across the Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Beth Israel Deaconess Medical Center, and Massachusetts General Hospital. These three institutions see over 4,000 new patients with breast cancer each year, and well over 15,000 patients are seen for ongoing therapy and/or follow-up visits. The DF/HCC, a NCI-designated comprehensive cancer center, provides a linking structure for all three institutions. All investigators in the Breast SPORE conducting clinical trials or other research studies involving human subjects use the Clinical Studies Core. These studies include those specifically identified in SPORE projects, as well as studies supported by the NCI-Avon Progress for Patients program. The Core also provides support to selected non-SPORE DF/HCC investigators who are conducting trials that involve the acquisition of research biopsies. In addition, the Core identifies and obtains consent from patients for participation in our DF/HCC cohort studies, and research databases (Clinical Research Information System [CRIS] and Risk Evaluation and Cancer History [REACH]). The Core seeks to minimize delays in the activation of protocols, streamline patient recruitment, and consent studies across multiple institutions. The work of this Core assures that clinical studies in the SPORE are conducted expeditiously and with rigor, enhancing the likelihood that the clinical trials and their linked laboratory-based research will be successful.

COHORT STUDIES AND DATA BASES

Breast Cancer Cohort concentrates its efforts in three areas: (1) enrolling new patients for blood draws, banking of specimens, and clinical data collection; collecting clinical data for patients with banked specimens; and, responding to user requests for data. Our database now includes medical information for approximately 15,003 patients, and baseline survey data on an additional 9,094 patients seen for one-time consultations.

High Risk Cohort manages our Risk Evaluation and Cancer History (REACH) project. Only individuals at highest risk, who are evaluated in the Cancer Risk and Prevention Clinic in the Gillette Center of the Dana-Farber Cancer Institute, are eligible to participate. The Core collects questionnaire data from all clinical subjects. This includes family history and exposure data. Those with highest risk in specific categories are asked to provide 2-3 tubes of blood. These specific categories include strong family cancer history, early age at cancer diagnosis, family clustering of rare cancers with breast cancer, histologic lesions (ADH, LCIS) and therapeutic radiation to the chest (e.g., Hodgkin’s Disease survivors).

Databases maintained by the Core include a “high risk” application in the Clinical Research Information System (CRIS). Both cohorts use the CRIS-linked Specimen Tracking and Inventory Program (STIP) application, thus allowing us to better support translational research projects using fully annotated specimens. Pedigree data for the high-risk cohort is kept in a separate Progeny database that links family pedigrees with cancer risk modeling software and rigorously protects patient confidentiality.

BIOSTATISTICS AND BIOINFORMATICS

This Core provides consultation and collaboration on quantitative methods plus analysis of high throughput genomic data to all SPORE investigators, Projects, and Cores. Biostatistical and bioinformatic expertise is available for the planning, conduct, analysis, and reporting of laboratory, animal, clinical, and epidemiological studies for SPORE Projects. The Core consults with researchers for the evaluation of computer databases, publicly available statistical programs and genomic data, and data integration. In addition, the Core collaborates with researchers to develop statistical/bioinformatic programs to address specialized problems.

COMMUNICATIONS, PLANNING AND ADMINISTRATION (CPA)

This Core is charged with administrative oversight and performance management of the Projects, Cores, NCI-Avon Progress for Patients supplements, Career Development awards and Developmental Projects awards under this collaborative, multi-institutional translational grant. For administrative oversight, the Core relies on the skilled and experienced staff in the Department of Medical Oncology Grants Administration at the Dana-Farber Cancer Institute (DFCI) to support the SPORE Director in the management of budgets and subcontracts. For best practices, the staff strictly adheres to generally accepted accounting principles that provide clear financial reporting and oversight. For performance management of the Projects and Cores, the SPORE Director relies on Advisory Committees to assist him in evaluating their progress. There are three advisory committees set up with defined roles: the Breast Program/SPORE Steering Committee, the External Advisory Board, and the Breast SPORE Director’s Leadership Counsel. In addition to the SPORE Director’s advisory groups, the Breast SPORE Core Coordinating Committee meets to review Core utilization and to discuss any issues that are of concern to the respective Cores. The Core provides vital integration of the SPORE with DF/HCC and the Program in Breast Cancer. Annually, the SPORE co-sponsors with the DF/HCC Program in Breast Cancer and the DFCI Women’s Cancers Program, a symposium in breast cancer research.

The Core supports our Breast Cancer Advocacy Group. Currently, we have 15 active advocates in our group. Our Advocates regularly attend SPORE meetings, planning retreats, mini-Retreats, EAB retreats, and our annual breast cancer research symposium. Our Advocates are formally assigned to Projects and Cores with a researcher liaison available to assist in answering questions. Many of our Advocates have completed Project LEAD. Our Advocates have attended an annual course on “Breast Cancer: Current Controversies and New Horizons,” the annual ASCO Breast Cancer Symposium, and the annual San Antonio Breast Cancer Symposium.