Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer
Condition: Triple Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Study type: Observational

Summary: 
      This study will determine if patient-derived tumor xenograft (PDX) mouse models can serve as
      a reliable model for treatment response for individual patients with triple negative breast
      cancer. The collection of patient tumor tissue will also provide insight into the mechanisms
      of therapeutic resistance for those individuals. Ultimately, this study will enhance our
      understanding of the genomic basis for treatment response for triple negative cancer on an
      individual basis, while having the potential to suggest new therapeutic options for high-risk
      triple negative breast cancer patients with residual disease post neoadjuvant.
    

Detailed description: 
      Triple negative breast cancer (TNBC) represents an aggressive, genomically heterogeneous,
      subtype of breast cancer with limited therapeutic options. Many patients with TNBC receive
      standard neoadjuvant chemotherapy (NAC) pre-operatively; response is directly correlated with
      long-term outcome. Patients with residual disease after NAC are at higher risk for recurrent
      or metastatic disease, but additional adjuvant therapies are not currently part of standard
      care. Personalized treatment for patients with TNBC requires an improved understanding of the
      genomic landscape of individual TN breast tumors, as well as improved predictive models of
      response to specific therapeutic agents. This pilot study will determine if patient-derived
      tumor xenograft (PDX) mouse models can serve as a reliable model for treatment response for
      individual patients with TNBC. The tumor tissue collected (paired pre-and post NAC) will also
      provide insight into mechanisms of therapeutic resistance for individual patients. This study
      will enhance our understanding of the genomic basis for treatment response for TNBC on an
      individual patient basis, and lead to potential new therapeutic options for high-risk TNBC
      patients with post-NAC residual disease.

      Objectives:

        1. To collect and bank tissue specimens from patients with operable triple negative breast
           cancer at: a) at time of diagnosis, prior to the start of neoadjuvant therapy and b) at
           time of definitive surgery, after the completion of neoadjuvant therapy.

        2. To collect and bank tissue specimen for patients with advanced metastatic triple
           negative disease prior to start of any line therapy for metastatic disease.

        3. To create patient-derived xenograft (PDX) mouse models utilizing specimens collected
           pre- and post- neoadjuvant treatment

        4. To determine if response of PDX tumors to cytotoxic agents in the Champions Oncology
           Tumor GraftTM (COTG) assay correlates with responses observed in patients.

        5. To perform genomic analyses of patient tumor specimens collected pre- and post
           neoadjuvant treatment to study mechanisms of drug resistance
    

Intervention name(s): Chemotherapy
Intervention type(s): Other
Intervention description(s): Patients are treated with neoadjuvant chemotherapy as according to the standard of care guidelines. Patients with metastatic disease are treated according to standard of care guidelines.
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with Triple Negative Breast Cancer that are eligible for neoadjuvant chemotherapy
        or have evidence of metastatic disease will be pursued for this protocol.
      
Biospecimen description: 
      Core Biopsy Specimen, Surgical Specimen
    
Keywords: Triple Negative Breast Cancer; Patient Derived Xenograft; Neoadjuvant Chemotherapy; Therapeutic Resistance