Scientists have identified a potential ‘therapeutic target’ for a form of breast cancer which is particularly difficult to treat, according to new research.
It is hoped the study – involving Nottingham Trent University, Nottingham University Hospitals NHS Trust and the University of Nottingham – may pave the way for a new vaccine to treat patients with ‘triple negative breast cancer’ (TNBC).
The findings, reported in the journal Clinical Cancer Research, show how the presence of a cancer-specific protein appears to predict how well patients with TNBC will respond to chemotherapy. As a result, it could help spare some of these patients from undergoing unnecessary treatment – which can carry serious side-effects – when their response is expected to be poor.
TNBC affects 12% of the 1.4 million newly-diagnosed breast cancer cases each year. There are very limited treatment options because this form of cancer does not express any of the three protein markers that are required for conventional targeted therapies to work.
The Nottingham study focused on the ‘HAGE’ molecule, which is known for its ability to drive cancer – and for its capacity to trigger immune responses.
The research team analysed tumour tissue from more than 1,000 patients with TNBC, who had or had not received some form of chemotherapy.
The study showed that patients who expressed high levels of the HAGE protein – but who hadn’t received chemotherapy – were at a much higher risk of dying from their disease, when compared to those who did not express the protein.
Patients who expressed HAGE and received anthracycline-based chemotherapy, meanwhile, were at a lower risk of death than those who did not express the protein.
The scientists also found that the expression of the protein was linked to the presence of immune cells (lymphocytes) infiltrating the tumours. These cells have the potential to attack tumour cells and their presence has been associated with better clinical outcomes in a number of cancer settings.
The immunogenic qualities of HAGE and its high protein expression in tumours have prompted the researchers to propose that HAGE provides a basis on which to generate a new therapeutic vaccine for TNBC and develop a combined chemotherapy/vaccine approach for its treatment.
“This is the first study to identify HAGE expression as a promising prognostic biomarker for triple negative breast cancer, and suggests the protein can predict benefit for chemotherapy patients,” said Professor Robert Rees, the Director of the John van Geest Cancer Research Centre at Nottingham Trent University.
He said: “There is an urgent need for individualised therapy for TNBC patients. The immunogenic potential of HAGE and its high protein expression in tumours, compared to normal tissue, could make it an ideal target for a vaccine.”
Professor Stephen Chan, consultant oncologist at Nottingham City Hospital, Nottingham University Hospitals NHS Trust – and a visiting professor at Nottingham Trent University added: “The management of TNBC remains a major clinical challenge and is hindered by the inability of these tumours to respond to traditional therapies. We have highlighted the discovery of a protein which may be of significance in stratifying patients for appropriate therapy.
“Given the HAGE protein’s immunogenic qualities, we should consider targeting it along with other cancer specific antigens for immunotherapeutic intervention, in conjunction with chemotherapy.”
The study involved the John van Geest Cancer Research Centre at Nottingham Trent University, the Clinical Oncology Department at Nottingham University Hospitals and the School of Medicine at the University of Nottingham.