Assay May Determine Which Triple Negative Breast Cancers Respond To Platinum Chemotherapy

Steven Jay Isakoff, MD, PhDHematology/Oncology Department of Medicine Massachusetts General Interview with:
Steven Jay Isakoff, MD, PhD
Hematology/Oncology Department of Medicine
Massachusetts General Hospital

Medical Research: What is the background for this study? What are the main findings?

Dr. Isakoff: Metastatic triple negative breast cancer remains a challenging clinical problem with no specific therapies targeted validated for this population.  From a number of preclinical studies and because of a link between BRCA1 associated breast cancer and triple negative breast cancer, platinum chemotherapy has emerged as a potential chemotherapy with activity in triple negative breast cancer.  However, it is not yet clear how to predict which triple negative breast cancer patients are more likely to respond to platinum chemotherapy.  We set out to answer several questions.

  • First, what is the response rate to platinum chemotherapy in the first or second line for metastatic triple negative breast cancer?
  • Second, can we identify biomarkers to predict response to platinum agents?  The results of our study showed that among 86 patients treated with platinum chemotherapy (either cisplatin or carboplatin), the response rate was about 25%.  We identified 11 BRCA mutation carriers in our population and the response rate among carriers was about 55% compared to about 20% in the non-carriers.  In addition, we found that a new assay called the Hologous Recombination Deficiency assay, which may identify tumors with a BRCA-like phenotype, seemed to predict which cancers were more likely to respond, whereas other biomarkers we looked at were not able to do so.
  • Another exciting finding was that 6 patients who had major responses have become long term responders with no subsequent progression, some whom for over 5 years so far.  Surprisingly, none of the long term responders are BRCA mutation carriers.

Medical Research: What should clinicians and patients take away from your report?

Dr. Isakoff: Our study confirms that platinum chemotherapy is a very reasonable option for patients with metastatic triple negative breast cancer, and that there may be a subset of patients who can achieve long term major responses for many years.  In addition, the HRD assay may be one way to help select which patients may benefit from platinum chemotherapy and which patients are not.  Although we think of platinum as traditional cytotoxic chemotherapy and not as a ‘targeted therapy’, our data would suggest that for some patients platinum may be highly active and in effect it may be like a targeted therapy.  The challenge is in figuring out who those patients are in advance.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Isakoff: Our study raises several questions that need to be addressed in future studies.  First, is the HRD assay predictive of platinum chemotherapy specifically or can it predict response to other DNA damaging agents in general?  This will be addressed in ongoing studies in the neoadjuvant setting.  In addition, a major unanswered question is what accounts for the exceptional responders?  Further analysis with next generation sequencing may hope to answer this question.


TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer

Steven J. Isakoff, Erica L. Mayer, Lei He, Tiffany A. Traina, Lisa A. Carey, Karen J. Krag, Hope S. Rugo, Minetta C. Liu, Vered Stearns, Steven E. Come, Kirsten M. Timms, Anne-Renee Hartman, Darrel R. Borger, Dianne M. Finkelstein, Judy E. Garber, Paula D. Ryan, Eric P. Winer, Paul E. Goss, and Leif W. Ellisen

JCO JCO.2014.57.6660; published online on April 6, 2015;

[wysija_form id=”1″] Interview with:, & Steven Jay Isakoff, MD, PhD (2015). Assay May Determine Which Triple Negative Breast Cancers Respond To Platinum Chemotherapy