title: 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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00901264.
authors.affiliation: Wilshire Oncology Medical Group-US Oncology, La Verne, CA, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Bosserman
authors.affiliation: Nashville Oncology Associates, Nashville, TN, United States of America.
authors.forename: Karl
authors.initials: K
authors.lastname: Rogers
authors.affiliation: Nashville Oncology Associates, Nashville, TN, United States of America.
authors.forename: Carl
authors.initials: C
authors.lastname: Willis
authors.affiliation: Tennessee Plateau Oncology, Crossville, TN, United States of America.
authors.forename: Dirk
authors.initials: D
authors.lastname: Davidson
authors.affiliation: Nashville Breast Center, Nashville, TN, United States of America.
authors.forename: Pat
authors.initials: P
authors.lastname: Whitworth
authors.affiliation: Wilshire Oncology Medical Group-US Oncology, La Verne, CA, United States of America.
authors.forename: Misagh
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Wilshire Oncology Medical Group-US Oncology, La Verne, CA, United States of America.
authors.forename: Gargi
authors.initials: G
authors.lastname: Upadhyaya
authors.affiliation: Data Vision, Dayton OH, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Rutledge
authors.affiliation: DiaTech Oncology, Montreal, Canada and Nashville, TN, United States of America.
authors.forename: Allan
authors.initials: A
authors.lastname: Hallquist
authors.affiliation: DiaTech Oncology, Montreal, Canada and Nashville, TN, United States of America.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Perree
authors.affiliation: Wilshire Oncology Medical Group-US Oncology, La Verne, CA, United States of America; DiaTech Oncology, Montreal, Canada and Nashville, TN, United States of America.
authors.forename: Cary A
authors.initials: CA
authors.lastname: Presant
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay / Q000379:methods*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents