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

PLoS One. 2015 May 29;10(5):e0122609. doi: 10.1371/journal.pone.0122609. eCollection 2015.

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Biological Assay / methods*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / drug therapy

Substances

  • Antineoplastic Agents

Associated data

  • ClinicalTrials.gov/NCT00901264

Grants and funding

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. Co-authors Allan Hallquist, Mathieu Perree, and Cary A. Presant, MD, FACP are employed by DiaTech Oncology LLC. DiaTech Oncology prepared the master protocol which was presented to and modified if desired by principle investigators. Data was collected by the laboratory (laboratory results sent also to the physicians and principal investigators in each site). Clinical response data was collected by the principal investigators in each site and provided to DiaTech Oncology to be included in the master protocol data spreadsheet with laboratory results which was then sent to the independent statistician for analysis. The decision to publish was the decision of the principal investigators in each site. The preparation of the manuscript was a responsibility of the principal investigators and was facilitated and reviewed by the co-authors at DiaTech Oncology. Co-author Dr. James Rutledge owns Data Vision. Data Vision provided support in the form of salary for author JR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author is articulated in the ‘author contributions’ section.