New breakthrough research in cancer

Angelina Jolie, who has never had cancer before, decided to have a preventive double mastectomy because she has a BRCA1 gene mutation, which puts her at increased risk for breast cancer. Photo: Filepic/AFP

In 2013, American actress Angelina Jolie, who has never had cancer before, decided to have a preventive double mastectomy because she has a BRCA1 gene mutation, which puts her at increased risk (87%) of developing breast cancer. And, in 2015, she had her ovaries and fallopian tubes removed to reduce her risk of developing ovarian cancer, the disease that killed her mother at the age of just 56.

During that time, there were only two genes that were usually tested for cancer risk in an individual – BRCA1 and BRCA2.

But fast-forward six years later, a new global study on cancer gives new options to individuals from families with a high-risk of getting cancer.

Known as Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES), the study, which was published in the prestigious New England Journal of Medicine, comprises over 113,000 participants from all over the world, including Asian participants from Malaysia.

Cancer Research Malaysia chief scientific officer professor Datin Paduka Dr Teo Soo Hwang co-led the Bridges study. Photo: Cancer Research Malaysia

“Today, Asians make up 50% of the world’s population but only 10% of the genomics and genetics research. However, this study which is currently the world’s largest, addresses that, ” says Cancer Research Malaysia chief scientific officer, Prof Datin Paduka Dr Teo Soo Hwang, who co-led the study.

“With a collaboration involving two hospitals in Malaysia and seven hospitals in Singapore, we’ve been able to increase the proportion of Asians in the studies from less than two per cent in 2015 to 14% in 2020, ” she says.

Dr Teo was happy to add that the Asian component was led by Malaysians: University of Malaya Medical Centre, Subang Jaya Medical Centre and Cancer Research Malaysia.

According to Dr Teo, the study is very important as it analyses the 34 genes commonly found in gene panel tests, narrowing it down to just 12 genes associated with breast cancer risk.

The BRIDGES study was led by Professor Douglas Easton, director of the Centre for Cancer Genetic Epidemiology, University of Cambridge and funded by Wellcome Trust and the European Commission. The Malaysian component of the study was made possible through the support of research grants and funding from the Wellcome Trust, Yayasan Sime Darby, Yayasan Petronas, and Estee Lauder Group of Companies.

Previously, genetic tests for cancers and other diseases have been offered to patients without any genetic counselling or a complete understanding of what recommendations to take in terms of prevention and screening.

The study’s findings will inform doctors, clinicians and companies that offer genetic tests, about the right set of genes associated with breast cancer risk, to better serve patients and their families.

Key findings

There are three key findings of the study:

Firstly, there are 12 genes associated with breast cancer.

“If a woman has a mother, sister or aunt affected by breast cancer, in the past, the doctor could only have tested for two genes (BRCA1 and BRCA2) but with the new research, doctors can now test 12 genes, ” says Dr Teo.

“Previously, it would be assumed that everyone in the family is at high risk because of the two genes. But now, because we can test 12 genes, we know some have developed cancer because of other genes. And some family members will have the gene while the rest might not have inherited it, ” she says.

“This helps us manage the families more accurately because we know exactly which gene happens in the family, how much risk is associated with the genetic change, what information can be provided to the family, and if they’re a gene carrier or not, ” she explains.

Secondly, some of the 12 genes are associated with all types of breast cancer while others with only certain types of cancer, so preventive strategies for gene carriers may be different depending on the gene.

“While BRCA1 and BRCA2 increases risk to the main sub-types of breast cancer, some of the 12 genes don’t increase risk to all cancers, they only increase risk to certain types of breast cancer, ” says Dr Teo.

“Hence, preventive strategies for these carriers need to be different according to the gene that they inherit. Currently, very little is known about preventive strategies by genes, so a major part of future research will be to find better ways of preventing breast cancer in an individual, so that they don’t have to resort to prophylactic mastectomy like Angelina Jolie, ” she adds.

Thirdly, risk of cancer is lower in Asians compared to Europeans, and more research in Asians is needed.

"Asians are just as likely as Caucasians to have genes predisposed to cancer, but have a significantly lower 45%-65% lifetime risk of developing breast cancer, compared to Caucasians at 65%-87%. This means screening and prevention recommendations must be tailored differently for Asian women, ” she says.

“The risk of breast cancer is Asians is significantly lower than that of the European population, but studies in the Asian population are smaller in size than that of the European population, so understanding what the risks are, is relatively low, and more research on Asians is needed, ” says Dr Teo.

“Since population-based screening is not practiced in Malaysia, women need to take the initiative to know their risk factors and go for opportunistic testing, ” says Dr Nur Aishah. Photo: Cancer Research Malaysia

Know your risk factor

Director of the Universiti Malaya Cancer Research Institute professor Dr Nur Aishah Mohd Taib, one of the Malaysian investigators in the study says: “With this study, we’re now able to better identify high-risk individuals. Since population-based screening is not practiced in Malaysia, women need to take the initiative to know their risk factors and go for opportunistic testing.”

“Many women with a family history of cancer have very little information about how to access screening and genetic testing. But they still need to know their risk factor, whether there is a strong family history of breast cancer or other cancer clusters (breast-ovary cancers, colorectal cancer, sakuma cancer, childhood cancers such as leukaemia) in their family and they need to see a doctor to assess their risk.

“Their genes can be tested in a specially-tailored intensive screening, ” she says.

“Patients can also attend risk management training and seek out specialists who are well-versed and can recommend risk reducing surgeries or other treatments, ” she adds.

According to Dr Nur Aishah, genetic testing is now more accessible in Malaysia.

“Previously the cost of two tests could come up to RM5,000, but now, it’s about RM1,000 for all 12 genes within the panel, ” she says.

But both panelists stress that breast cancer isn’t just determined by a single factor like genetics. There are multiple factors that may cause cancer, including having fewer children at an older age, having one’s period at a younger age, or having menopause at a later age, and also physical activity and alcohol consumption.

Possible solutions

The Bridges study reveals that there are 12 genes that can be tested to assess one's risk to cancer. Photo: Cancer Research Malaysia

The future risk of cancer can be reduced by 80-85% through surgery to remove the ovaries and fallopian tubes, like what Angelina Jolie did.

“But the challenge for women is whether they should do this at the early age of 35 (because the risks increase after 30). This is a difficult decision because it means loss of fertility and early menopause for a young woman who is still in her prime, ” says Dr Nur Aishah.

“Also, while surgery to remove of both breasts can prevent breast cancer, it’s not 100%, ” she says.

“Risk can also be managed by intensive screening. Besides the mammogram, there is also the magnetic resonance imaging (MRI) for BRAC1 carriers and these can be done annually after the age of 30, ” she adds. “Those who have BRCA2 genes can also use medication to reduce the risks.”

Support required

More future patients and donors are urged to step forward to support the research on breast cancer in Asians. Photo: Pixabay

Dr Teo encourages future patients and donors to come forward to support the research on breast cancer in Asians.

“We hope more patients will contribute their tissue and blood samples for the research to improve survival rates for patients, ” she says.

“Although it’s fearful to find out we may have inherited a gene that causes a high risk of cancer, the reality is that carriers have as good a chance as other patients of surviving the disease. And, breast cancer survival rate is improving tremendously with medical development, ” she concludes.

For more info, visit: Cancer Research Malaysia