Application of a drug-induced apoptosis assay to identify treatment strategies in recurrent or metastatic breast cancer

Abstract

Background: A drug-induced apoptosis assay has been developed to determine which chemotherapy drugs or regimens can produce higher cell killing in vitro. This study was done to determine if this assay could be performed in patients with recurrent or metastatic breast cancer patients, to characterize the patterns of drug-induced apoptosis, and to evaluate the clinical utility of the assay. A secondary goal was to correlate assay use with clinical outcomes.

Methods: In a prospective, non-blinded, multi institutional controlled trial, 30 evaluable patients with recurrent or metastatic breast cancer who were treated with chemotherapy had tumor samples submitted for the MiCK drug-induced apoptosis assay. After receiving results within 72 hours after biopsy, physicians could use the test to determine therapy (users), or elect to not use the test (non-users).

Results: The assay was able to characterize drug-induced apoptosis in tumor specimens from breast cancer patients and identified which drugs or combinations gave highest levels of apoptosis. Patterns of drug activity were also analyzed in triple negative breast cancer. Different drugs from a single class of agents often produced significantly different amounts of apoptosis. Physician frequently (73%) used the assay to help select chemotherapy treatments in patients, Patients whose physicians were users had a higher response (CR+PR) rate compared to non-users (38.1% vs 0%, p = 0.04) and a higher disease control (CR+PR+Stable) rate (81% vs 25%, p<0.01). Time to relapse was longer in users 7.4 mo compared to non-users 2.2 mo (p<0.01).

Conclusions: The MiCK assay can be performed in breast cancer specimens, and results are often used by physicians in breast cancer patients with recurrent or metastatic disease. These results from a good laboratory phase II study can be the basis for a future larger prospective multicenter study to more definitively establish the value of the assay.

Trial registration: Clinicaltrials.gov NCT00901264.

Conflict of interest statement

Competing Interests: The authors have the following interests: DiaTech Oncology LLC provided research support by processing the test(s) in the laboratory and providing an independent statistician for analysis of data and results. Dr. Cary Presant is Chief Medical Officer at DiaTech, Dr. Allan Hallquist is Director of Pathology at DiaTech, and Mathieu Perree is Director of Laboratory at DiaTech. Dr. James Rutledge owns Data Vision, Dr. Linda Bosserman is president of Wilshire Oncology Medical Group. Dr. Karemi and Dr. Upadhyaya are employees of Wilshire Oncology. Dr. Presant is an independent contractor under contract with Wilshire Oncology. Dr. Karl Rogers and Dr. Carl Willis are with Nashville Oncology Associates. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT Flow Diagram.

Fig 2. Time to recurrence in patients with recurrent or metastatic breast cancer.

Blue curve, patients whose physician used the MiCK assay. Red curve, patients whose physician did not use the MiCK assay.

Fig 3. Overall survival in patients with recurrent or metastatic breast cancer.

Blue curve, patients whose physician used the MiCK assay results for next treatment after assay. Red curve, patients whose physician did not use the MiCK assay results for next treatment after assay.