Journal article
Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer
E Nolan, P Savas, AN Policheni, PK Darcy, F Vaillant, CP Mintoff, S Dushyanthen, M Mansour, JMB Pang, SB Fox, CM Perou, JE Visvader, DHD Gray, S Loi, GJ Lindeman
Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2017
Abstract
Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1-Associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, we explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1-deficient tumor model. BRCA1-mutated triple-negative breast cancers (TNBCs) exhibited an increased somatic mutational load and greater numbers of tumor-infiltrating lymphocy..
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Awarded by Breast Cancer Research Foundation
Funding Acknowledgements
This work was supported by the Australian National Health and Medical Research Council (NHMRC) (grants 1016701, 1040978, and 1078763), the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS), the Victorian State Government through the Victorian Cancer Agency and Operational Infrastructure Support, the Breast Cancer Research Foundation (New York), the Qualtrough Cancer Research Fund, the Joan Marshall Breast Cancer Research Fund, and the Australian Cancer Research Foundation. E.N. was supported by a Cancer Council Victoria Scholarship and a Cancer Therapeutics CRC Top-Up Scholarship. A.N.P. was supported by a Cancer Council Victoria Scholarship. P.K.D. was supported by NHMRC Fellowship 1041828. S.B.F. was supported by NHMRC Fellowship 1079329. C.M.P. was supported by funds from the NCI Breast SPORE program (P50-CA58223-09A1 and RO1-CA195740-01). J.E.V. was supported by NHMRC Australia Fellowship 1037230 and is currently supported by NHMRC Elizabeth Blackburn Research Fellowship 1102742. D.H.D.G. was supported by NHMRC Career Development Fellowship-2 (1090236). S.L. was supported by a John Colebatch Cancer Council Victoria Clinical Fellowship. G.J.L. was supported by NHMRC Fellowship 1078730.