Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer

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

Inclusion Criteria:

- a histological diagnosis of invasive triple negative breast cancer determined by
standard immunohistochemical analysis.

- must be candidates for neoadjuvant chemotherapy according to standard of care
guidelines or have evidence of metastatic disease.

- must agree to a biopsy for research purposes at time of diagnosis and to undergo
surgery at the hospitals of the Mount Sinai Health System.

Patients with the following MAY be eligible:

- a histological diagnosis of ER and/or PR positive breast cancer with an overall receptor
expression ≤ 30% breast cancer determined by standard immunohistochemical analysis

Exclusion Criteria:

- concurrent disease or condition that would make the patient inappropriate for study
participation,

- any serious medical or psychiatric disorder that would interfere with the subject's
safety, or inability to provide informed consent.

- vulnerable populations will not be included.