Women with a type of breast cancer that is particularly difficult to treat and who have a BRCA1 or BRCA2 mutation are much more likely to respond to chemotherapy drug carboplatin than current standard treatment, initial results from a major, phase III clinical trial reveal.
In a presentation at one of the top international annual cancer conferences, the San Antonio Breast Cancer Symposium in Texas, the leader of one of the most significant ever trials in women with advanced metastatic triple-negative and BRCA1 or BRCA2 mutation associated breast cancer will announce first analysis of its results.
The trial included women who had triple negative breast cancer or BRCA mutations. Women who have BRCA mutations and develop breast cancer often have the triple-negative type.
An analysis across all 376 women who entered the trial found that taking carboplatin did not seem to have any benefit over a current standard treatment in this setting, docetaxel.
But in a subgroup of around 40 women with BRCA mutations, most of whom had triple-negative breast cancer, the effect was very noticeable – with around two thirds responding to carboplatin, compared with around a third who responded to docetaxel.
The trial involved more than 70 hospitals across the UK and was co-ordinated by researchers at The Institute of Cancer Research, London, and King’s College London.
It was led by Professor Andrew Tutt, Director of the Breakthrough Toby Robins Breast Cancer Research Centre at The Institute of Cancer Research (ICR), and was largely funded by Cancer Research UK and Breakthrough Breast Cancer.
Professor Tutt will say that the findings represent a significant step forward in researchers’ efforts to treat some forms of triple-negative breast cancer more effectively.
They could allow doctors to divide triple-negative breast cancer – a poorly understood set of different cancer types that is currently treated as one entity and tends to be particularly difficult to treat – into subgroups of women who could benefit from more biologically driven treatments.
In the trial, which closed to recruitment earlier this year, a total of 376 women were allocated to receive treatment with up to six three-week cycles of treatment with either carboplatin or docetaxel.
The data from the trial has undergone statistical analysis at the ICR’s Clinical Trials and Statistics Unit, which also defined the overall methodology for the trial.
Triple negative breast cancer accounts for around 15 per cent of breast cancer cases – 7,500 cases every year in the UK. It is so called because it does not fall into any of the three main treatment-defining classes of breast cancer. These are categorised by the presence of proteins called ER, PR or HER2 on the surface of cancer cells, which are used to select current effective targeted drugs such as trastuzumab and endocrine therapies. Approximately 10-20 per cent of women with triple negative breast cancer have mutations in BRCA1 or BRCA2.
Trial leader Professor Andrew Tutt, Director of the Breakthrough Toby Robins Breast Cancer Research Centre at The Institute of Cancer Research, London, said:
“Our trial has found a new way to personalise treatment for a significant minority of women with advanced triple negative breast cancer, for whom comparatively few treatments are available. It shows that women with this cancer type who also have a mutation in either of the BRCA1 or BRCA2 genes should have the option of taking a different form of chemotherapy than that often prescribed now for advanced disease.
“Triple negative breast cancer is generally difficult to treat and represents a huge area of unmet need. It is a major focus of our research, and it is enormously gratifying to show there is a better treatment available for some patients.”
Professor Judith Bliss, Director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, who is leading the analysis of the results, said:
“Our findings are a step forward in our understanding of how best to treat triple negative breast cancer, which accounts for around 15 per cent of breast cancers. It opens the door to a more effective treatment for some women based on the biology of their disease, mirroring the biologically targeted treatments already available for more common forms of breast cancer.”
Professor Nazneen Rahman, Professor of Human Genetics at the Institute of Cancer Research, London, who performed the BRCA gene testing for the study, said:
“One of the things this study has shown is how important it is to know whether or not a BRCA gene mutation has caused triple-negative breast cancer. We need BRCA testing to be available to all women with this type of breast cancer.”
Professor Peter Johnson, Cancer Research UK’s chief clinician, said:
"We are learning more and more about the different types of breast cancer and how changes in the genes can affect the results of treatment. This study is exciting because it takes that knowledge and uses it to find better treatment for a type of cancer that is especially difficult. Clinical trials like this are vital in helping us to develop more effective treatments and improve survival rates for this type of breast cancer.”
Dr Simon Vincent, Assistant Director of Research at Breakthrough Breast Cancer, said:
“Breakthrough has long supported research like this which further analyses women living with triple negative breast cancer and teaches us more about how best to tackle this aggressive form of the disease.
“Women living with this type of breast cancer may feel discouraged that effective treatments for their disease are few and far between – but this study shows that for some women, there are now more options available to treat them better.”