The study will be valuable in directing future research efforts to improve our understanding of this cancer sub-type, which accounts for around seven per cent of breast cancer cases but is relatively poorly understood.
Its unusual appearance under the microscope – with groups of inside-out cells immersed in a spongy mesh – has long baffled scientists, and it has a particularly poor prognosis because current treatments are often ineffective.
Scientists in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London, alongside international colleagues, carried out a range of complex genetic experiments on samples from 16 patients with micropapillary carcinomas of the breast. The study, newly published in the Journal of Pathology, has previously received a prestigious award and was funded by Breakthrough Breast Cancer and Breast Cancer Campaign.
The scientists were looking for consistent genetic changes that could be driving the tumours across different patients. In particular, they were looking for mutations in any of 273 genes that have recently been identified to be involved in more common subtypes of breast cancer, and the production of any specific cancer-causing ‘fusion’ genes, which are created by the erroneous joining-up of different sections of DNA.
They did not find any specific mutations, or any commonly occurring fusion genes, However, they discovered eight definite fusion genes in the samples, each of which could be involved in driving cancer cells to produce more copies of themselves, and some of which could ultimately be targeted by new treatments.
One of these fusions involved the disruption of the DNA repair related gene CDK12 and was found to be recurrent in a subset of patients who also tested positive for amplifications of the HER2 gene. Tests in cancer cells suggested that patients with disruption of CDK12 may benefit from treatment with a targeted type of drug called a PARP inhibitor, and suggested this possibility should be explored in further research.
Study leader Dr Rachael Natrajan, Team Leader in the Division of Breast Cancer in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London, said:
“It’s vitally important we find new treatments for less common cancers like micropapillary carcinomas of the breast, as there is a big gap in the options available. The chances of surviving this type of breast cancer are relatively low, and although comparatively it’s a rare type, because breast cancer is so widespread it still affects many thousands of women in the UK each year.
“Our study brings us a little closer to understanding the genetic events that drive this disease, and give important clues that will guide future research. It shows that fusion genes are an important factor, and seem to be driving the particularly aggressive behaviour shown by cancer cells of this type. It also provides a rationale for further exploring the potential of PARP inhibitor drugs in a sub-group of patients.”