The research, presented yesterday (Thursday 10 December 2015) at The 2015 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas, aimed to assess the usefulness of a prognostic test called EndoPredict in women with oestrogen receptor (ER) positive, HER2 (human epidermal growth factor receptor 2) negative breast cancer, and to compare this with another test, Oncotype DX.
The tests predict the likelihood of a woman’s breast cancer returning and inform decisions about whether chemotherapy should be offered to her in addition to standard hormone treatments such as anastrozole or tamoxifen. EndoPredict, manufactured by Sividon Diagnostics and distributed by Myriad Genetics, analyses the activity of eight different genes within a tumour sample, and uses this information alongside a patient’s tumour size and nodal status to give an ‘EPclin’ score estimating their risk of developing secondary breast cancer.
The EPclin score is then used to categorise patients into low or high risk groups, with a cut-off point of 10% risk over 10 years. Those with a low risk could potentially avoid unnecessary chemotherapy treatment, while higher risk patients would be recommended to go ahead with chemotherapy to lower their increased risk of developing secondary disease, for which there is currently no cure.
The research was led by Professor Mitch Dowsett from at The Institute of Cancer Research and The Royal Marsden in London, and Professor Jack Cuzick from Queen Mary University of London. The researchers analysed tumour samples from 928 patients diagnosed with ER positive, HER2 negative primary breast cancer using EndoPredict.
The patients originally took part in the Arimidex, Tamoxifen Alone or in Combination (ATAC) clinical trial and were treated with five years of anastrozole or tamoxifen, and their Oncotype DX recurrence score was already available for comparison. EndoPredict and Oncotype DX were used to identify patients with a low risk of recurrence over 10 years, of less than 10%.
When Oncotype DX was used to identify the third of lymph node-negative patients with the lowest risk of secondary disease, 7% went on to develop secondary breast cancer after 10 years. Of the third of patients identified as having the lowest risk according to the EPclin score, only one of 227 (0.5%) patients developed secondary disease.
By identifying a large group of patients with a very good prognosis, EPclin could offer clinicians and particularly patients reliable reassurance that chemotherapy can be avoided. In addition, EndoPredict could potentially be carried out locally at a qualified molecular pathology lab, turning the results around within days and allowing a treatment plan to be devised promptly.
Conversely, the Oncotype DX test is carried out at just one laboratory in the US and once the samples have been sent abroad for analysis, results take up to 14 days to be returned. The samples tested form part of the ‘TransATAC’ collection of patient samples, the establishment of which was originally funded by Breast Cancer Now, with additional funding from AstraZeneca, and has received infrastructural support from the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR).
Much of the research was conducted at the Breast Cancer Now Toby Robins Research Centre at the ICR. Professor Mitch Dowsett, Head of the Centre for Molecular Pathology and Head of the Academic Department of Biochemistry at The Royal Marsden and The Institute of Cancer Research, London, said:
“Our study showed that a new test, which analyses a range of breast cancer genes alongside other tumour features, is more accurate than the current NHS standard test at detecting the risk of relapse for women with a common type of breast cancer. When we widened out analysis to include pathological features such as tumour size, the test became more accurate at predicting disease than other exclusively gene-based tests.
“The most striking result was that the new test, called EndoPredict, was particularly accurate at defining women at low risk of cancer spread if their disease had never invaded the local lymph nodes in the breast – with cancer spreading to a new site in only one of 227 patients in this group over 10 years. This demonstrates the potential of the test to give patients and their doctors excellent reassurance that they do not need extra chemotherapy after initial treatment to keep cancer at bay.”
Katherine Woods, Senior Research Communications Manager at Breast Cancer Now, said:
“Whilst it’s possible that more evidence to support the use of EndoPredict will be required before it is considered for routine use in the UK, research like this is essential if we are to constantly improve the accuracy with which patients are treated.
“Personalised medicine is the direction we need to be moving in if we are going to give breast cancer patients the best chance of survival, while crucially avoiding overtreatment, and ultimately outwit this disease once and for all in the future.”
Oncotype DX is approved for a subgroup of breast cancer patients by the National Institute for Health and Care Excellence (NICE) for use on the NHS in England and Wales as a cost effective tool to determine a patient’s risk of breast cancer recurrence.
EndoPredict is yet to be formally assessed by NICE and is therefore only currently available privately in the UK. Any patients who think they could benefit from either of these tests should speak to their clinician.
Breast Cancer Now is very grateful to The Trustees of The Mary-Jean Mitchell Green Foundation for their exceptionally generous support of Professor Mitch Dowsett’s research.