Assessing an Asian breast cancer patient's risk of having the BRCA gene

Prof Teo and Prof Nur Aishah have a look at the results of a genetic test in this filepic. The development of ARiCa helps predict more accurately which Asian breast cancer patients are likely to have a faulty BRCA gene.

When it comes to breast cancer, data shows that one in 25 patients inherit a faulty BRCA (BReast CAncer) gene.

However, breast cancer patients are usually only offered a genetic test if they are diagnosed at a young age or have close relatives with breast or ovarian cancer.

But as age and family history alone does not accurately predict the likelihood of carrying a faulty gene, this means that many gene carriers are not offered the test, missing the opportunity for life- saving treatments in patients and prevention strategies in their close relatives.

Study lead and Cancer Research Malaysia (CRM) chief scientific officer Professor Datin Paduka Dr Teo Soo Hwang shared: “Using criteria such as age and the presence of family history of breast cancer, we estimate that each year, nearly 4,000 newly diagnosed breast cancer patients in Malaysia would need genetic counselling and testing, but they often don’t consider a genetic test because most assume that they are unlikely to have inherited a faulty gene.”

The BRCA genes are tumour suppressor genes that help keep breast, ovarian and other types of cells from growing and dividing too rapidly or in an uncontrolled way.

Faulty ones don’t do this job properly, thus increasing the risk of cancer.

To overcome this challenge, a number of mutation prediction tools have been developed, but the majority of them are built for European women and are less accurate for women of Asian descent.

As a result, Asian patients and their family members miss out on the opportunity of being aware of their genetic risk status, thereby losing the possibility for cancer prevention and accurate treatment selection.

To tackle this challenge, CRM collaborated with 12 local, British and Singaporean institutions, to analyse the BRCA1 and BRCA2 genes in more than 8,000 breast cancer patients from Malaysia and Singapore.

The results, published in the Journal of Clinical Oncology, were then used to develop a tool called ARiCa – short for Asian Genetic Risk Calculator.

“With ARiCa, we can now give each woman their individual likelihood of being a BRCA carrier, so that they can be empowered to make informed choices about their health, and healthcare practitioners can provide more accurate treatment plans for their patients,” said Prof Teo.

Co-principal investigator Dr Li Jingmei from the Genome Institute of Singapore added that: “This collaborative research that took place between Malaysia and Singapore hospitals, allowed us to gather test data from a multi-ethnic population of Malay, Chinese, and Indian breast cancer patients.

“This ensures that the tool developed performs equally well across Asian ethnic subgroups.”

Co-study lead and University of Cambridge, United Kingdom, Centre for Cancer Genetic Epidemiology director Prof Douglas Easton noted that until recently, more than 90% of genetic studies had been conducted in European women.

His colleague and lead developer of the Boadicea and CanRisk tools in European women Prof Antonis Antoniou added: “Tools like CanRisk are now widely used in Europe, North America, Australia and other countries.

“This research points the way on how we can adapt CanRisk for more accurate risk assessment in women from Asian countries.

“The information may be particularly important for adapting the tools for low- and middle- income countries where the funding and infrastructure may not be able to support screening for every woman.”

Effect on treatment

Knowledge of a patient’s BRCA status can have an effect on their breast cancer treatment.

Consultant breast surgeon Datuk Dr Yip Cheng Har explained: “From the clinical perspective, knowing that a patient has a BRCA mutation may alter their surgical management.

“For instance, a patient with a BRCA mutation has a 50% likelihood of developing breast cancer on the opposite breast.

“An acceptable prevention strategy is to remove both breasts with an option of immediate breast reconstruction.

“But because a BRCA carrier also has a 30-40% risk of developing ovarian cancer, removal of the ovaries can be done at the same time.

“In addition to changing the available surgical options, medical practitioners can also prescribe the patient a new class of drugs called PARP inhibitors, which target the BRCA mutation to improve survival in carriers with early and late stages of breast cancer.

“Since we cannot provide cancer genetics services for all patients, ARiCa can help us to identify patients that need to be referred for genetic counselling and testing.”

Universiti Malaya Cancer Research Institute head Prof Dr Nur Aishah Mohd Taib added: “Prophylactic surgery and targeted therapy may not be routinely available in government-funded and public hospitals, but knowing the BRCA mutation status is important for patients and family members.

“This is in order for them to be aware of their individual risk that enables early detection of cancer and other risk management strategies.

“At Universiti Malaya, we have been running a risk management clinic for more than 10 years to help affected and unaffected carriers get access to risk-reducing strategies, and we hope that tools like ARiCa will enable other hospitals to set up similar clinics.”

For free genetic counselling provided by CRM, click here or call 012-374 7426/016-363 4742.