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

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.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Other: Chemotherapy

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

• Study Type: Observational
• Enrollment (Actual): 68

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Triple Negative Breast Cancers; All women eligible for this protocol will fall into this group. These women will have histologically confirmed triple negative breast cancer and be eligible for neoadjuvant chemotherapy or have evidence of metastatic disease.	Other: Chemotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Tumor Response	Tumor response in patients will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model Tumor Response	Tumor response in models will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response	Day 1

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Champions Oncology
• Investigators: Principal Investigator: Hanna Yoko Irie, MD, PhD, Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai; Principal Investigator: Elisa Port, MD, Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): January 22, 2019
• Study Completion (ACTUAL): January 22, 2019

Study Registration Dates

• First Submitted: September 19, 2014
• First Submitted That Met QC Criteria: September 19, 2014
• First Posted (ESTIMATE): September 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Triple Negative Breast Cancer; Neoadjuvant Chemotherapy; Patient Derived Xenograft; Therapeutic Resistance
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: GCO 14-0686