A group of Malaysian scientists from Subang Jaya Medical Centre, Cancer Research Malaysia in collaboration with the University of Cambridge in the UK have built the largest genetic and genomic database of Asian breast cancers to-date.
The milestone helps doctors to diagnose patients more precisely and offers the most effective treatment option.
Prior to this, the majority of characterised genomes (the sum total of an organism’s DNA) used in breast cancer research were from Caucasian women with less than five per cent Asians.
The collaborative effort between scientists in Malaysia and the UK led to mapping the genomes of 1,000 breast cancer patients.
As a result, Asian representation in genomic studies has now increased exponentially.
According to the lead researcher Prof Datin Paduka Dr Teo Soo Hwang, Asians only made up two per cent of breast cancer genomic research in 2015, but at the end of 2020, Malaysians accounted for nearly 20 per cent of total breast genomic maps that have been published globally so far, with Korea and China at 13 per cent.
Highlighting the importance of having such a database, Dr Teo said breast cancer is a heterogeneous disease, which means there are many types of it that cannot just be looked under a microscope to diagnose the type.
“This is where genetics and genomics come in to help analyse the genome or DNA of cancer cells and determine what has gone wrong.
“So even though some cancers look the same under a microscope, they are different in the genomes and this helps us decide on how best to treat cancers,” said Dr Teo, who is also Cancer Research Malaysia chief scientific officer.
In the past, she said all patients with breast cancer might have been given one drug, with some patients responding, some having no response and others suffering from side effects.
“Today, with advancements in precision medicine, it is possible to determine which drug may work best for each patient, so that each one can get an appropriate response and an opportunity for improved survival.”
According to her, genomic information enables doctors to be more precise in diagnosis, as well as choosing the right treatment for the right patient.
“It is critical for us to close the gap in Asian genomic research, otherwise we may miss important genetic information that may be rare in Caucasians, but common in Asians.”
Dr Teo said the genomic map helps doctors to discover three things they never knew about Asian breast cancers.
First, she said Asians were more likely to have an aggressive type of breast cancer, those that express the HER2 receptor (human epidermal growth factor receptor 2).
“Patients with HER2 positive breast cancers experience 18 per cent lower overall survival compared to others, and we know very little about this disease such as its risk factors and reasons Asians are more likely to get this aggressive subtype of breast cancer.
“The more research we do, the more we know, and the more lives we can save through targeted therapy.”
Secondly, Dr Teo said Asians were more likely to have a mutation in the gene called TP53.
“Our research showed that one in three Asian breast cancer patients have this gene alteration, and TP53 mutated cancers are more likely to result in poor survival.
“There is currently no treatment that is targeted at these cancers, so we need to continue exploring the possibilities.”
Lastly, she said the study showed that Asian cancers are more likely to have active immune cells compared to Europeans, which was true for all subtypes of breast cancer.
“This discovery has already led to a new clinical trial to test immunotherapy in Asian breast cancer patients, called Auror.
“The trial started in July last year and is led by Cancer Research Malaysia in partnership with oncologists at the Clinical Investigation Centre of University Malaya Medical Centre and National University Hospital Singapore.”
Whilst mapping the genome of Asian breast cancers is a big step for medical research, Dr Teo hinted that they are not stopping there.
She said they already have started using the information to determine new treatment options for patients.
“Through the genomic map and more research, we now know that a genetic marker called APOBEC3B is four times more common in Asians and it causes breast cancers to be surrounded by immune cells.
“But somehow these immune cells don’t recognise that their neighbour is a cancer cell that needs to be destroyed.”
She said they have now launched their first clinical trial to test whether reactivating the immune system in these Asian patients will improve treatment response for patients with metastatic breast cancer.
“Our genomic map has shown us that there are many footprints that are left in the DNA.
“Our DNA is constantly attacked by the carcinogens in the food that we eat and our living environment.”
According to Dr Teo, the genomic methods can separate the genomic footprints and identify patients who respond to a new type of treatment.
She also noted that Cancer Research Malaysia will be launching two other clinical trials in a bid to find more effective treatment options for Asian cancer patients.
The move will be in line with their continuous efforts in cancer prevention, developing an AI-powered app to aid telemedicine and creating a tool to improve breast cancer risk prediction for Asian women.
The study published in the Nature Communications science journal, was a collaboration between Cancer Research Malaysia, Prof Carlos Caldas and Dr Suet-Feung Chin from the University of Cambridge Cancer Research UK Cambridge Institute, Dr Pathmanathan Rajadurai and Prof Emeritus Dato’ Dr Yip Cheng Har from Subang Jaya Medical Centre.