Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy

Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, CT, USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.

Triple negative breast cancer is so called because it lacks molecular characteristics that are associated with response to modern targeted treatments. Hatzis and colleagues selected individual tumors from patients who had exhibited either good or poor sensitivity to cytotoxic chemotherapy, and characterized 29 cases of the disease by whole exome sequencing, with validation in further groups of patients. Patients with a newly-defined "BRCA deficient" subtype experienced better survival with chemotherapy, and had a higher burden of mutations and neoantigens that could be targeted by the immune system. Based on these findings, the authors suggest that immunotherapies might be tested in patients with BRCA deficient, triple negative breast cancer.

In a commissioned Perspective article, Mack Su and David Fisher of Massachusetts General Hospital, Boston, MA, USA discuss developments in cancer immunotherapy, an area which has had a long history. During the past decade there have been notable advances in the treatment of melanoma, an aggressive tumor type which is increasing in incidence in some populations. Alongside development of drugs which target the BRAF mutations that are common in melanoma, therapies have been discovered that stimulate the immune response to tumors--blocking so-called checkpoints, or inhibitors of the immune response. Su and Fisher describe the potential for use of different combinations of immune and targeted therapies and conclude that, as new immunotherapies are developed and tested in different tumor types, "deeper mechanistic insight will be required to inform clinical decisions."

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This work was supported in part by grants from the Breast Cancer Research Foundation to CH, LP and WFS and from the Lion Heart Fund for Cancer Research to CH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

All authors have read the journal's policy and the authors of this manuscript have the following competing interests: WFS reports stock and intellectual property in Nuvera Biosciences, Inc.

Jiang T, Shi W, Wali VB, Pongor LS, Li C, Lau R, et al. (2016) Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis. PLoS Med 13(12): e1002193. doi:10.1371/journal.pmed.1002193

Department of Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut, United States of America
MTA TTK Lendulet Cancer Biomarker Research Group, Research Center for Natural Sciences,
Budapest, Hungary
2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
Department of Genetics, Yale School of Medicine, Yale University, New Haven, Connecticut, United States of America
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
Yale Cancer Center, New Haven, Connecticut, United States of America

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002193

The authors gratefully acknowledge support from NIH grants 5P01 CA163222, 5R01 AR043369-19, and T32GM007753, and grants from the Melanoma Research Alliance, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors have declared that no competing interests exist.

Su MY, Fisher DE (2016) Immunotherapy in the Precision Medicine Era: Melanoma and Beyond. PLoS Med 13(12): e1002196. doi:10.1371/journal.pmed.1002196

Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002196