Core 1: Stanford Breast Metastasis Center Biospecimen and Pathology Core

Project Summary/Abstract
In order to investigate the processes of breast cancer metastatic relapse, longitudinal cohorts of breast tumor
tissue with detailed clinical information are needed. Thus, an integral function of the Stanford Breast Metastasis
Center (SBMC) will be the acquisiton, processing, clinical annotation, and curation of hundreds of breast tumors
collected across multiple sites and stages of disease progression. To this end, this project describes the aims
and functions of the SBMC Biospecimen and Pathology Core. The Core will be led by experienced breast
pathologist Dr Gregory Bean, who will implement and iteratively improve standard operating procedure protocols
for processing, pathologic review, and generation of tissue microarrays for the Core samples. The lab of principal
investigator Dr Christina Curtis will assist in sample collection and processing to enable numerous downstream
multi-omic protocols, in which they have extensive expertise, as well as breast organoid generation. Breast
medical oncologist Dr Jennifer Caswell-Jin and breast surgeon Dr Irene Wapnir will recruit participants to
prospective tissue acquisition protocols and will design and review clinical annotation procedures. The Core will
draw samples from six established efforts, including two completed clinical trials (TRIO B07 and TONIC), two
prospectively recruiting clinical trials (NCT04504331 and TERPSICHORE), an existing Institutional Review
Board (IRB)-approved protocol whereby archival tumor specimens are collected retrospectively, and an existing
IRB-approved protocol whereby prospective serial tumor and blood samples are collected from consented
patients with breast cancer undergoing routine care. In Aim 1, longitudinal tumor samples throughout treatment
and metastasis will be collected from these sources. Prospectively collected samples will be subjected to rapid
processing to include formalin fixation, cryopreservation, and preservation of viable cells for organoids; H&E
slides will be scanned and reviewed for tumor cellularity and tumor-infiltrating lymphocytes; standardized
immunohistochemistry will be performed; and detailed information about location and orientation will be
recorded. In Aim 2, a highly integrated database will be constructed to provide linkage of these collected
biospecimens with high quality demographic, clinical, pathologic, and treatment data. This secure Research and
Electronic Data Capture database will include detailed clinical information and will link biospecimens via
barcodes to the Laboratory Information Management System, where information on all downstream assays
performed on samples is stored. In Aim 3, a framework for sharing high quality, de-identified biospecimens and
clinical data within the SBMC will be established. Summaries of de-identified clinical metadata that can be shared
with investigators across the SBMC will be generated, and rapid identification of project-specific cohorts enabled.
Successful completion of these Aims will result in an annotated, longitudinal breast cancer biospecimen cohort
with unprecedented molecular and clinical annotation and the potential to reveal new insight into the metastatic
niche and breast cancer evolution.

Grant Number: 5U54CA261719-05
NIH Institute/Center: NIH
Principal Investigator: GREGORY BEAN