Breast cancer study shows need to expand gene screening

Feb 23 2015

Professor Rodney Scott, left, and Dr Cliff Meldrum with the gene sequencer

Hunter researchers have identified a significant new risk factor for triple-negative breast cancer (TNBC), impacting women who would currently fall outside genetic testing benchmarks for the disease.

Potentially deadly BRCA1 and BRCA2 gene mutations were found in almost 10 per cent of TNBC patients included in the study. Of those, 59 per cent of the mutation carriers had no prior family history of breast cancer.

In addition the average age of diagnosis for those harbouring BRCA2 mutations was 58 – similar to the general population of TNBC patients – whereas BRCA1 and BRCA2 mutation carriers are more commonly associated with younger age.

The term “triple negative” refers to breast cancer cells lacking the expression of three common receptors (oestrogen, progesterone and HER2). With targeted hormonal therapies currently being ineffective, typical treatment comprises a combination of surgery, radiotherapy and chemotherapy.

“If these women had gone to their GP they probably would’ve been told they had no increased risk of developing breast cancer,” Professor Rodney Scott*,

Director of Genetics with Pathology North and co-leader of HMRI’s Information Based Medicine program, said. “But this finding suggests that a significant proportion do, in fact, carry a familial risk and also should not be precluded because of age.

“Many would only find out once they had developed the disease because there’s been insufficient evidence to provide early testing, so we believe the triple-negative phenotype should now be added as a criterion to BRCA gene screening guidelines.”

The study was facilitated by state-of-the-art Next-Gen sequencing technology recently acquired at HMRI, using more than 750 DNA samples sourced from the Australian Breast Cancer Tissue Bank and the Pomeranian Medical University in Szczecin, Poland.

The results, published in the international journal Breast Cancer Research and Treatment, shed light on a long-standing conundrum, according to Professor Scott.

“We’ve known for about 20 years that women with an inherited BRCA predisposition tended to have a tumour type similar to TNBC, yet no one took the next logical research step because the testing was prohibitively expensive,” he explained.

“It previously cost around $2000 per patient and a project like this would have tallied to over $1.5 million. Our study was done at a fraction of that cost using the new technology – it’s a game-changer in our ability to screen more people without ‘blowing the budget’, so to speak.

“Thousands of women could benefit from knowing about their mutation status, especially if they’re young and planning a family of their own.  Furthermore, clinical trials are underway, using specific therapies that target BRCA1 or BRCA2, which are tailored to the genetic nature of the disease.”

* Professor Rodney Scott is Director of Genetics with Pathology North and co-Director of the University of Newcastle’s Priority Research Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine. Dr Michelle Wong-Brown from the University of Newcastle and Dr Cliff Meldrum from Hunter New England Health also worked on the study. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.