Genetic testing to help prevent and reduce breast cancer risk
Breast cancer results from genetic variations in cells resulting in uncontrolled cell growth leading to development of a tumour within the breast tissue. It is the most common cancer in Sri Lankan women accounting for 24% of all female cancers.
Genetic factors play an important role in the causation of breast cancer. Cancer predisposition genes are genes in which variations confer highly or moderately increased risks of breast cancer, usually greater than a two-fold risk.
Oscar-winning actress Angelina Jolie who found out through genetic testing that she was at high risk for breast cancer decided to undergo a prophylactic bilateral mastectomy to reduce her risk of developing the disease
There are three types of breast cancer: hereditary, familial and sporadic. About 5-10% of all breast cancers are hereditary due to inheritance of rare variations in breast cancer predisposition genes such as BRCA1, BRCA2, TP53, CDH1, STK11 and PALB2, while 20– 30% are familial due to a combination of rare variations in genes such as ATM, CHEK2, BRIP1 as well as lifestyle risk factors. The remaining breast cancers, accounting for 70-80% mostly occur sporadically in women with no known family history of the disease and are mainly attributed to multiple common variations in breast cancer susceptibility genes conferring 1 to 2-fold increased risk.
Recent advances in cancer genetics research have shed light on the biological mechanisms responsible for many breast cancers. This has helped to transform breast cancer care from primary prevention, to screening and diagnosis, to treatment and follow-up using genetic information gathered by testing patients, their families, and the tumour tissue itself. It has led to early detection of at-risk individuals with an inherited predisposition to breast cancer and provision of genetic counselling for undergoing regular cancer surveillance or prophylactic interventions to reduce cancer risk. It has also facilitated the treatment decision-making process and administration of appropriate personalized treatment based on the patient’s genomic profile, prediction of response to specific treatment strategies and disease prognosis.
The vibrant cancer genetics research team at the Human Genetics Unit of the Colombo Medical Faculty, under the leadership of Prof. Vajira H.W. Dissanayake, the current Director of the Unit, has introduced the latest genomic technologies for the implementation of these novel genomic services in the country. Genetic counselling and diagnostic services for cancer and various other genetic disorders are currently available at the Human Genetics Unit, Faculty of Medicine, University of Colombo.
A positive family history usually indicates possibility of hereditary breast cancer. Women with a history of breast cancer in a first-degree relative (parents, children or siblings) are at approximately two-fold higher risk than women without a family history. Besides family history, other common characteristic features include earlier age of onset (<50 years), bilateral breast cancer and multiple cancers in an individual such as both breast and ovarian cancer. The identification of specific genes associated with hereditary breast cancer has enabled direct diagnosis of hereditary breast cancer syndromes through genetic testing. Knowledge of the genetic variations in families with hereditary breast cancer is vital for selecting appropriate treatment strategies and for the early detection of inherited cancer risk in close relatives.
Genetic testing is done on DNA extracted from peripheral blood using Next-Generation Sequencing (NGS)-based testing. It provides a rapid and cheaper alternative to single-gene tests as it can analyse multiple cancer predisposing genes simultaneously at a lower cost. It allows testing for variations in genes which could be an indicator of inherited susceptibility to breast cancer. An affected family member is tested first. If a genetic variation is found, then other family members, including those who are not affected, can be tested for that genetic variation. In addition, pharmacogenomic tests are available in which the tumour tissue is tested to select appropriate treatment targeted at the genetic variation driving the cancer as well as predict response to treatment and modify where needed.
Genetic counselling allows individuals an opportunity to learn how genetics contributes to cancer risk, understand their personal risk of developing cancer, options for managing the cancer risk and encourages adoption of appropriate behaviours to reduce the risk. All individuals undergoing genetic testing should be offered pre-test and post-test genetic counselling.
International guidelines for assessing individualized breast cancer risk and planning appropriate personalized treatment and screening options based on the genomic profile are now available. Such knowledge is vital not only for the treatment and follow up of breast cancer affected patients but more importantly for screening of at-risk healthy family members with a hereditary predisposition to breast cancer.
Awareness of their genetic risk status will allow such family members to make informed decisions regarding reproduction, lifestyle and risk-reduction strategies to prevent future occurrence of cancer through chemoprevention and surgical procedures such as prophylactic mastectomy. Implementing genomic-based strategies for improved surveillance, early detection, and selection of appropriate treatment options will help to significantly prevent and reduce the burden of breast cancer in the country.
(The writer is Senior Lecturer and Clinical Geneticist, Human Genetics Unit/Dept. of Anatomy, Faculty of Medicine, University of Colombo)