KUALA LUMPUR, Jan 27 — Cancer Research Malaysia, together with the University of Cambridge and Subang Jaya Medical Centre, have built the largest genetic and genomic database of Asian breast cancers to date.
Previously, the majority of characterised genomes (the sum total of an organism’s DNA) used in breast cancer research were from Caucasian women – less than 5 per cent came from Asians, even though Asians make up more than half of the world’s population.
“Genomic information enables us 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. Through our study, we discovered that Asians are at higher risk of an aggressive type of breast cancer, are more likely to have a mutated TP53 gene, and have an enriched immune tumour profile. Our publication opens the door to improving precision medicine for Asian breast cancer patients,” said Prof Dr Teo Soo Hwang, Chief Scientific Officer at Cancer Research Malaysia, who led the study.
The study, published in the Nature Communications science journal, was a collaboration between Cancer Research Malaysia, Professor Carlos Caldas and Dr Suet-Feung Chin from the Cancer Research UK Cambridge Institute, University of Cambridge, Prof Pathmanathan Rajadurai and Prof Emeritus Dr Yip Cheng Har from Subang Jaya Medical Centre.
The genomic sequences of 560 breast cancer tumour samples were analysed and it was discovered that the aggressive subtype that expresses the HER2 protein is more common in Asian women compared to Caucasians.
“The HER2 subtype of breast cancer is one of the most aggressive, and it is becoming clear that the risk factors may be different from other types of breast cancer. Our study highlights that Asians have a higher risk of this type of aggressive disease and underscores the need to do more research in Asians so that we can save more lives,” said Dr Yip, consultant breast surgeon at Subang Jaya Medical Centre.
The research also showed that the TP53 gene – often called the “guardian of the genome” because it protects normal cells from becoming cancer cells – is more commonly altered in Asian breast cancers compared to that of Caucasians.
“TP53 is frequently mutated in the more aggressive hormone negative breast cancers in Caucasian women. In Asian breast cancer patients, we observe an increase in TP53 mutations in hormone receptor positive cases and is associated with poorer survival,” said Dr Chin, who co-led the study.
“We also observed that Asian breast cancers are more likely to have immune cells present, and this suggests that if we can find some way to lift the invisibility cloak that cancers have to evade detection by the immune system, we may be able to improve survival for Asian breast cancer patients,” said Dr Pan Jia Wern, the study’s first author and the Deputy Head of Bioinformatics at Cancer Research Malaysia.
The researchers noted that this genomics map has enabled new thinking about the treatment of breast cancers in Asians. For example, a new clinical trial to test immunotherapy in Asian breast cancer patients has already started in July 2020, led by Cancer Research Malaysia, in partnership with oncologists at Universiti Malaya and National University Hospital Singapore. But more can and should be done.
“Today marks an important milestone in our mission to save lives through research in Asians. We aim to continue to ensure that genomics research is more diverse and inclusive so that all populations can benefit from the advances in technology,” said Prof Dr Teo.
The team at Cambridge was led by Dr Chin and Prof Carlos Caldas, where excellent core facilities enabled the extensive genomic profiling done. “We were delighted to participate in this important study, which I called the Asian METABRIC, since it parallels our efforts to extensively characterise breast cancer and stratify tumours into one of the 11 Integrative Clusters,” said Prof Caldas.
The study was supported by research grants and charitable funding from the UK Medical Research Council via the Newton-Ungku Omar Fund, Scientex Foundation, Yayasan Sime Darby, Yayasan PETRONAS , Cancer Research UK and Estee Lauder Group of Companies. Read the study here.