Breast cancer could be detected up to five years before there are any clinical signs of it, using a blood test that identifies the body’s immune response to substances produced by tumour cells, according to research presented at the 2019 NCRI Cancer Conference.
Cancer cells produce proteins called antigens that trigger the body to make antibodies against them – auto-antibodies. Researchers at the University of Nottingham (UK) have found that these tumour-associated antigens (TAAs) are good indicators of cancer, and now they have developed panels of TAAs that are known already to be associated with breast cancer to detect whether or not there are auto-antibodies against them in blood samples taken from patients.
In a pilot study the researchers, who are part of the Centre of Excellence for Autoimmunity in Cancer (CEAC) group at the School of Medicine, University of Nottingham, took blood samples from 90 breast cancer patients at the time they were diagnosed with breast cancer and matched them with samples taken from 90 patients without breast cancer (the control group).
They used screening technology (protein microarray) that allowed them to screen the blood samples rapidly for the presence of autoantibodies against 40 TAAs associated with breast cancer, and also 27 TAAs that were not known to be linked with the disease.
Presenting the research at the NCRI Conference, Daniyah Alfattani, a PhD student in the group, said: “The results of our study showed that breast cancer does induce auto-antibodies against panels of specific tumour-associated antigens. We were able to detect cancer with reasonable accuracy by identifying these auto-antibodies in the blood.”
The researchers identified three panels of TAAs against which to test for autoantibodies. The accuracy of the test improved in the panels that contained more TAAs. The panel of five TAAs correctly detected breast cancer in 29% of the samples from the cancer patients and correctly identified 84% of the control samples as being cancer-free. The panel of seven TAAs correctly identified cancer in 35% of cancer samples and no cancer in 79% of control samples. The panel of nine antigens correctly identified cancer in 37% of cancer samples and no cancer in 79% of the controls.
“We need to develop and further validate this test,” said Alfattani. “However, these results are encouraging and indicate that it’s possible to detect a signal for early breast cancer. Once we have improved the accuracy of the test, then it opens the possibility of using a simple blood test to improve early detection of the disease.” The researchers are now testing samples from 800 patients against a panel of nine TAAs, and they expect the accuracy of the test to improve with these larger numbers.
“A blood test for early breast cancer detection would be cost effective, which would be of particular value in low- and middle-income countries. It would also be an easier screening method to implement compared to current methods, such as mammography,” said Alfattani. The researchers estimate that, with a fully-funded development programme, the test might become available in the clinic in about four to five years.
A similar test for lung cancer is currently being tested in a randomised controlled trial in Scotland, involving 12,000 people at high risk of developing lung cancer because they smoke. They have been randomised to have (or not) an auto-antibody blood test called ELISA (Early CDT-Lung). Participants who test positive for the auto-antibodies are then followed up with a CT scan every two years in order to detect lung cancer in its early stages when it is easier to treat.
The CEAC group is also working on similar tests for pancreatic, colorectal and liver cancers. Solid tumours like these, as well as lung and breast cancer, represent around 70% of all cancers. “A blood test capable of detecting any of these cancers at an early stage is the over-riding objective of our work,” concluded Alfattani.
Dr Iain Frame, CEO of NCRI said: “Early diagnosis using simple, non-invasive ways of detecting the first signs of cancer is a key strategic priority for NCRI and something we’d all like to see working in practice. The results from this pilot study for a blood test to detect early breast cancer are promising and build on this research group’s expertise in other cancers, such as lung cancer. It’s obviously early days but we look forward to seeing the results from the larger group of patients that are now being investigated.”
Background: Autoantibodies against numbers of tumour-associated antigens (TAAs) were shown to be relevant tumor biomarkers and can be detected up to 5 years before the tumour is overt clinically. Early diagnosis of cancer is paramount to improved survival by enabling treatment prior to cancer spreading, when tumours should be both surgically removable and curable. The NHS in Scotland is currently carrying out a RCT (ECLS) involving 12,000 individuals at high risk of developing lung cancer being randomised to having (or not) an autoantibody ELISA blood test (EarlyCDT-Lung®) – followed by CT scans over 2 years follow-up in those individuals with a positive test – for early lung cancer detection.
We are aiming to develop a blood test enabling the early detection of breast cancer to significantly improve clinical outcome.
Method: In this pilot study, 180 breast cancer matched control samples were screened for the presence of autoantibodies against 67 TAAs which have already been shown to involve in breast cancer pathology. Optimised Protein microarray technology was applied for this study.
Results: The results confirmed our hypothesis that BC induce autoantibodies (AAbs) against different panels of specific tumour associated antigens (TAAs) used in the pilot study. The assay provided cancer/control discrimination through detection of AAbs against TAAs.
Conclusion: We identified antigen panels of sufficient sensitivity and specificity for early detection of BC based upon serum profiling of autoantibody response. This opens the possibility of a blood test for screening and detection of breast cancer.
Daniyah Alfattani, CEAC group
Other researchers have urged caution in interpreting these results. “These are clearly very preliminary data,” said Cambridge University cancer epidemiologist Professor Paul Pharoah in a report in The Guardian. “A lot more research would be needed before any claim can be made that this is likely to represent a meaningful advance in the early detection of cancer.”
Warwick University molecular oncologist Professor Lawrence Young agreed: “While this is encouraging research, it is too soon to claim this test could be used to screen for early breast cancer. More work is needed to increase the efficiency and sensitivity of cancer detection.”
The Nottingham team is now testing samples from 800 patients and expect the accuracy of the test to improve with these larger numbers.
“A blood test for early breast cancer detection would be cost effective, which would be of particular value in low and middle-income countries. It would also be an easier screening method to implement compared with current methods, such as mammography,” said Alfattani.
The researchers estimate that, with a fully funded development programme, the test might become available in the clinic in about four to five years.
The group is working on similar tests for pancreatic, colorectal and liver cancers. Solid tumours such as these, as well as lung and breast cancer, represent about 70% of all cancers.
In addition, a similar test for lung cancer is being tested in a randomised controlled trial in Scotland, involving 12,000 people at high risk of developing lung cancer because they smoke. Participants who test positive for the auto-antibodies are have a CT scan every two years in order to detect lung cancer in its early stages when it is easier to treat. “A blood test capable of detecting any of these cancers at an early stage is the overriding objective of our work,” said Alfattani.NCRI material 2019 NCRI Cancer Conference abstract The Guardian report