Background

Triple-Negative Breast Cancer

Most breast cancers are associated with one of three proteins acting abnormally. These proteins are estrogen receptor (ER), progesterone receptor (PR), or a protein called HER2. Available treatments block the action of these proteins, which stops tumors cells from continually multiplying. However, a triple-negative breast cancer (TNBC) tumor produces little to no ER, PR, or HER2, so the three most-likely candidates that would cause the tumor are not responsible.

Because the causes of TNBC are so elusive, it is harder to treat. Consequently, TNBC has a much higher mortality rate than other types of breast cancer.

For a number of reasons, Hispanic women with TNBC experience worse outcomes than non-Hispanic Caucasian women. Compounding this disparity is the fact that Hispanic women are 30% more likely to be diagnosed with TNBC than non-Hispanic Caucasian women. The poor outcomes may also result from discrepancies in social determinants of health such as income, education, and diet.

Project

This project brings together a community of researchers, clinicians, patients and community advocates, who join forces as 'Project CELSUS' to apply precision medicine genomic profiling to identify novel treatments and implement a more precise and rational system to match TNBC tumors and cancer therapies. The project draws its name from Aulus Cornelius Celsus, an early pioneer of evidenced-based medicine in the 1st century A.D.

Since launching on August 14, 2019, the Project CELSUS team has made important strides towards developing project infrastructure and bringing together stakeholders from 14 separate institutions.

The Project CELSUS team plans to build on its 2020 accomplishments by improving their models, refining their system for testing the effectiveness of medications, validating their results in additional models, and continuing to strengthen engagement with partnering community hospitals. The work will support the ultimate goal of optimizing treatments for Hispanic women with TNBC.

Analyzing Existing Datasets

As an early action, Project CELSUS compiled and analyzed information about clinical breast tumors from several large, publicly available datasets including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, and Gene Expression Omnibus. The UCSD team has developed a prototype of a database that combines the information from the existing datasets with additional clinical data that had previously been collected by CELSUS team members. Project CELSUS has collaborated with UC San Diego Health Information Services and Amazon Web Services to develop a secure, HIPAA-compliant, cloud-based data repository to store and track patient samples.

Disease Model for TNBC

Project CELSUS also developed a disease model for TNBC that could help oncologists predict how a tumor would react to medication, or a combination of medications. The team used the data from their prototype database to design a model system classifying TNBC tumors into subtypes by identifying patterns within tumors' molecular signatures.

The researchers identified molecular signatures associated with a subset of particularly aggressive TNBC tumors and observed a potentially significant association between a patient’s ethnicity (African American and Hispanic ancestry), BMI, and tumor aggressiveness. The researchers plan to continually refine the classification system.

Of note, the team's model suggests that combining two specific medications–both already FDA-approved–could be highly effective against a type of TNBC tumor that is known to be particularly aggressive and resistant to other therapeutics.

Community Clinics

Project CELSUS has made progress toward its goal of strengthening the research capabilities of the community clinics on the collaborative team. The team members from the community clinics experience challenges when participating in research, mostly because the time they spend attending project meetings is time that can't be spent seeing patients. The Project CELSUS team has been working to create ways for the community investigators to efficiently receive subawards, share patient data and tissue samples, train staff, register research protocols, and send samples for sequencing to third-party vendors. In addition, through community outreach and engagements efforts, formal interviews in Spanish and English with community clinicians and Latina patients with breast cancer are being conducted across San Diego and Imperial county to learn about their experiences.

Research Team and Collaborators

Research Team

  • University of California, San Diego
    • Pablo Tamayo, PhD
    • William Kim, PhD

Collaborators

  • American Cancer Society
  • Cancer Resource Center of the Desert
  • El Centro Regional Medical Center
  • Michigan State University
  • Moores Cancer Center
  • Quality Partners
  • Rady Children’s Hospital
  • San Diego State University
  • Sanford Burnham Prebys Medical Discovery Institute
  • Tri-City Medical Center
  • University of Guadalajara

For more information about this content, please contact:

Shannon Muir, PhD
Shannon Muir is Co-Director of the California Initiative to Advance Precision Medicine. She coordinates the efforts of this demonstration project.