Immunotherapy hope for BRCA1 breast cancer patients

Researchers from the Walter and Eliza Hall Institute of Medical Research (WEHI) and the Peter MacCallum Cancer Centre have developed a breakthrough mode of breast cancer treatment which involves harnessing the patient’s own immune system.

Triple negative breast cancers in women with BRCA1 mutations are particularly aggressive, affecting around 15% of Australian breast cancer patients, and notoriously difficult to treat. This new method combines two immunotherapy drugs, immunotherapy having been successfully used in treating lung cancer and melanoma by boosting the body’s natural immune system.

Triple negative breast cancers have not responded to new targeted therapies as well as other types of breast cancer, but by combining anti-PD1 and anti-CTLA4 immunotherapies with chemotherapy, laboratory models of BRCA1-related tumours have seen significant improvement in halting growth. Anti-PD1 and anti-CTLA4 immunotherapies are described as ‘immune checkpoint inhibitors’ that reverse the effects of cancer cells that operate by ‘switching off’ immune cells that should be attacking tumours.

“BRCA1-related triple negative breast cancers have some of the most ‘chaotic’ genomes, and we see many immune cells accumulate in and around the tumour,” said study co-author Dr Daniel Gray. “This suggests that the immune cells can readily detect that something is awry, but they aren’t able to respond properly, because they have been disabled by tumour cells. We showed that a combination of anti-PD1 and anti-CTLA4 therapies restored their ability to attack and kill triple negative breast tumour cells, and very effectively control tumour growth.”

Associate Professor Sherene Loi added, “Our lab-based findings provide compelling evidence to progress to a clinical trial of this combination of immunotherapy drugs, and chemotherapy, in women with BRCA1-related breast cancer.”

Professor Geoff Lindeman of WEHI highlighted the collaborative nature of this research under the umbrella of the Victorian Comprehensive Cancer Centre (VCCC), noting, “Our study brought together researchers with diverse expertise across several institutions, including PhD students from the University of Melbourne. We also benefited from our close collaboration with kConFab, a national consortium focused on familial breast cancer.”

Published in Science Translational Medicine, the research was led by Dr Emma Nolan, Professor Geoff Lindeman, Dr Daniel Gray and Professor Jane Visvader of the Walter and Eliza Hall Institute, along with Associate Professor Sherene Loi and Associate Professor Phillip Darcy from the Peter MacCallum Cancer Centre. Additional support was provided by the Victorian State Government Operational Infrastructure Support Program, Qualtrough Cancer Research Fund, Joan Marshall Breast Cancer Research Fund, Breast Cancer Research Foundation (US), Australian Cancer Research Foundation, Cancer Council Victoria, and the National Health and Medical Research Council.

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