RSU Researchers Have Discovered a Previously Unidentified Mutation in the BRCA1 Gene that Contributes to the Development of Hereditary Breast Cancer
One of the scientists who has been included in the Latvian Science Calendar 2021 is Arvīds Irmejs, an Associate Professor at the Rīga Stradiņš University (RSU) Department of Surgery and a lead researcher at the Institute of Oncology. Irmejs is also an oncologist and breast surgeon at Pauls Stradiņš Clinical University Hospital. For 20 years, he and a large team of researchers from RSU have been researching genetically hereditary breast cancer and its prevalence in Latvia, and have made significant discoveries.
Breast cancer is the most common oncologic disease in women in both Latvia and worldwide. Every year about 1,100 Latvian women are diagnosed with breast cancer.
‘5% of all breast cancer patients genetically inherit the disease from their parents. There is no way to prevent it completely as of yet, but it is possible to predict it. This enables us to do everything possible to prevent the cancer from developing further, or to detect it very early,’ explains Assoc. Prof. Irmejs.
The research team at RSU has determined the prevalence of the disease, the most common gene mutations, and their features in Latvia by conducting extensive genetic testing of about 5,000 women.
Photo from the Latvian Science Calendar 2021 created by the Ministry of Education and Science. Photo: Toms Harjo
What are the features of hereditary breast cancer?
With hereditary breast cancer, a woman has up to 80% risk of developing it in her lifetime. In addition, women with inherited breast cancer develop it about 20 years earlier than average.
This occurs most frequently around the age of 45. However, the age range of when patients are diagnosed with hereditary breast cancer is very broad - sometimes this can be shortly after the patient turns 20, but in rare cases also after 60.
What helps prevent breast cancer and achieve better treatment results?
Diagnosing this disease early is very important. Breast cancer screenings allow for the disease to be detected even when the woman doesn’t have any complaints or symptoms yet. Prophylactic breast cancer exams are performed using mammography, which is an X-ray examination of breast tissue. It can detect changes in the breast even before these can be felt.
In Latvia, women between the ages of 50 and 69 get free mammography exams every two years. However, in order to take care of your own health, regular examinations should start earlier - from the age of 40. The fee is only four euros with a referral from a general practitioner.
Magnetic resonance imaging is, however, the main preventive test for people at risk of hereditary breast cancer and these should be performed every year from the age of 25.
The second pillar in breast cancer prevention is having a healthy lifestyle. This primarily includes diet, exercise and rest, but also reproductive health meaning the age at which women give birth, how long they breastfeed for, how many pregnancies they have had, or whether or not any hormone replacement therapies have been used during menopause, etc.
Why does hereditary breast cancer need to be researched?
20 years ago, only a few people in Latvia had an understanding of what hereditary breast cancer was. Our research has helped to define the relevance and the specific characteristics of this problem in Latvia. This has been of great importance in identifying people at risk.
Furthermore, it is important for researchers to study and understand what needs to be done in order to make hereditary cancer treatments less aggressive and as patient friendly as possible, while still being effective. For example, a study is currently underway to determine whether lymph node biopsies might help predict the effect of preoperative chemotherapy and, whether to perform a gentle axillary lymph node surgery. This study is being carried out by RSU doctoral graduate Baiba Līcīte.
You have recently published a significant discovery about hereditary breast cancer in Latvia. You have discovered a common but previously unidentified mutation in the BRCA1 gene that facilitates the development of hereditary breast cancer.
Yes, sometimes you can work for 10–20 years with very little apparent progress, but then suddenly favourable conditions or a coincidence can lead to unexpected and interesting discoveries. For example, in 2015 the international database ClinVar confirmed that one BRCA1 gene variant with previously unidentified significance actually facilitates the development of breast cancer.
Our research group and possibly other scientists in Latvia had already observed this change in the BRCA1 gene, but this had simply been ignored. This coincided with a time when new technologies made genetic testing cheaper and more accessible, and we also received financial support from RSU. This made it possible to genetically investigate almost 200 cases of suspected heredity. In 10% of the cases we discovered this “new” gene variant.
Therefore, we have now published the finding that the third most common inherited breast cancer-promoting pathogenic variant or mutation of the BRCA1 gene in Latvia is different from what we have believed for the past 20 years.
Thanks to this information, we can now optimise our screening strategy, making it faster and more cost-effective, and help more women at heightened risk of hereditary breast cancer.
Are gene mutations that increase the risk of inherited breast cancer country-specific?
Yes! In the publication I mentioned, RSU doctoral student Pēteris Loža compiled literature data on our neighbouring countries. Although the two most common mutations in the BRCA1 gene are identical in all countries in the region, it turned out that so far this “new” mutation has been found only in few cases in the other countries - much less frequently than in Latvia.
At the opening event of the Latvian Science Calendar 2021, RSU Vice-Rector for Science Agrita Kiopa wished for ‘every researcher to have a million euros’ because it makes life easier. What would you research if you and your team were given one million euros?
Enable genetic screening opportunities of inherited breast cancer for the population using innovative e-health tools. In theory, everything is quite clear. Initially, all Latvian women aged 25 to 60 would need to be genetically tested, and then all women aged 25. To put it simply, the cost of a genetic test is comparable to the cost of a COVID-19 test. In a few days, on million COVID-19 tests will have been performed in Latvia, but there would be far fewer genetic tests.
Identifying high-risk individuals before they develop breast and/or ovarian cancer would facilitate prevention or early diagnosis in 5% of breast cancer cases and 15% of ovarian cancer cases. This would not require additional funding. Although millions would be spent on diagnosis, treatment and sick leave expenses would be reduced significantly and GDP would increase. Patients should not be afraid of dying of hereditary breast or ovarian cancer and doctors should not be treating hereditary breast and ovarian cancer that is already in stage 3, or 4. In reality, however, everything is more complicated. Some women might not want to take part in screenings because they do not want to find out what their caner risk is. Some would take the test, but might not participate in regular exams. Others could be very anxious to know the results of a genetic test. It is therefore necessary to carry out a pilot project to evaluate the aforementioned aspects including a psychological evaluation of the participants at different stages of the process.
Is your research being overshadowed by the COVID-19 pandemic?
Competition for science funding has always been fierce, and oncology has not been a priority, especially last year. However, you should keep in mind that other diseases than COVID-19 still exist and that oncological studies with potential clinical use should receive more support.
What inspires you to continue your research?
I remember the names of many patients with hereditary breast cancer even from 10 years ago. There are also patients who send me text messages on their birthdays. Even after difficult treatment, the results are in many cases good.
Patients do not want to be diagnosed with cancer again, so they often choose preventive surgery. Studies have shown that this approach is effective.
In the last year, magnetic resonance imaging of several high-risk patients has detected breast cancer tumours within a 10mm-size range. This is satisfactory and gives me confidence that we must continue in the same vein as we have started.
Facts about Arvīds Irmejs
- Associate Professor at the Department of Surgery, RSU Faculty of Medicine
- Lead researcher at the RSU Institute of Oncology
- Surgeon at Pauls Stradiņš Clinical University Hospital since 2002
- Head of the Centre for Breast Diseases at Pauls Stradiņš Clinical University Hospital since 2008
- Repeated internship at the Department for Breast Diseases, University of Manchester (Great Britain), The Netherlands Cancer Institute in Amsterdam, Breast Disease Centre of Antwerp University Hospital in Belgium, etc.