Tuesday 23 February 2010
New research suggests that methods recently developed for the molecular classification of breast cancer may be unsuitable for selecting patients for clinical trials.
Dr Jorge Reis-Filho, from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR), says molecular tests to classify breast cancer subtypes need much more development to ensure they are accurate and consistent enough to be used in a clinical setting.
Much research has been carried out over the past decade into tests for molecular subtypes – basal-like, HER2, luminal A, luminal B and normal breast-like – based on expression of genes. It is hoped this system of classification will allow all patients who could benefit from a treatment to receive it, and for others who will not benefit to avoid unnecessary side effects. This is going to become ever more important as more targeted treatments are developed.
Three molecular tests for the identification of these subtypes have already been developed. The scientific and medical communities had assumed that these different methods would produce similar results. Dr Reis-Filho’s research, published today (Tuesday 23 Feb) online in the journal, Lancet Oncology, shows that different tests to identify the same molecular subtypes of breast cancer produce inconsistent results which vary widely.
The research suggests that stringent standardisation of the different tests for molecular subtypes of breast cancer is needed before they can be used in a clinical setting. Until that time, the classification currently used by doctors based on oestrogen receptor and HER2 should not be replaced by the proposed molecular classification. In fact, treatment decisions can be safely made based on currently available clinical tests and pathology.
Dr Reis-Filho said: “Our results show that although the molecular classification scheme is likely correct, tests based on expression of genes are not ready to be used for patients in clinical trials. The great danger is that clinical trials set up in this way may produce results that will delay the availability of individualised therapy for breast cancer patients. This would be a waste of time and money, and could lead to patients being denied drugs that could improve their outcome.
“Until tests for molecular subtypes of breast cancer are standardised they should not be used in a clinical setting.”
The researchers looked at three different tests for molecular subtypes and compared them in the same groups of tumour samples. For instance, they looked at samples from patients known to be HER2 positive by current methods. One of the molecular tests found half the patients not to be of HER2 subtype, while two others classified all the patients into different molecular subtypes. Therefore, if these new molecular tests were used on patients, there would be a significant risk they would not receive the treatment they need, such as Herceptin (trastuzumab). Likewise, the classification of luminal tumours into A, which have a good prognosis, and B, which have a bad outcome, was strongly dependent on the molecular method used to classify the cancers. Classifying these patients into incorrect groups could lead some to be denied chemotherapy when they would benefit from it; while others would be exposed to side-effects when they are unlikely to derive any benefit.
Dr Britta Weigelt, from Cancer Research UK’s London Research Institute, said: “Our results confirm that molecular subtypes of breast cancer do exist. However, there is still a long way before they can be applied in the clinic.
“Devising accurate methods to classify breast cancers into subtypes of therapeutic relevance should be a top priority in breast cancer research.”
ICR Chief Executive Professor Peter Rigby said: "Much work is being done to find new drugs that target a patient's specific molecular defects; however it is equally important to develop new, reliable tests to determine exactly who will benefit from these treatments. The ICR will continue to work with its partners to make sure diagnosis of breast cancer types is as precise as possible, which will ultimately improve patient care.”
-ENDS-
For more information or interviews, please call Richard Purnell in the Breakthrough Breast Cancer Press Office on 020 7025 0290 or email [email protected].
Notes to editor
About breast cancer
- Breast cancer is the most commonly diagnosed cancer in the UK – nearly 46,000 women and around 300 men are diagnosed every year
- Breast cancer accounts for nearly 1 in 3 of all female cancers and one in nine women in the UK will develop breast cancer at some point in their lifetime.
- More than 1,000 women die of breast cancer every month in the UK
- The good news is that more women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening
Breakthrough Breast Cancer
- Breakthrough Breast Cancer is a pioneering charity dedicated to the prevention, treatment and ultimate eradication of breast cancer. We fight on three fronts: research, campaigning and education
- We fund ground-breaking research, campaign for better services and treatments and raise awareness of breast cancer. Through this work the charity believes passionately that breast cancer can be beaten and the fear of the disease removed for good.
Find more information at breakthrough.org.uk
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
- The ICR has charitable status and relies on voluntary income, spending 95 pence in every pound of total income directly on research
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
For more information visit www.icr.ac.uk