Using Genetic Testing to create custom breast cancer treatment plans
By Dr Fatima Hoosain
Over the past decade, the field of oncology has undergone substantial changes in the way patients with cancer are treated. We have moved from a ’one-size-fits-all’ treatment approach to an era that has an increasing focus on precision medicine based on genomic variants[1].
To better understand cancer and to develop drugs that fight it, medical researchers have been studying genes and the changes in these genes for a very long time. The goal behind this research is to create therapies that disrupt various steps in cancer growth, whilst causing minimal damage to normal cells.
Researchers have noted that some types of cancers are frequently associated with specific genetic mutations. Not every cancer has a genetic source, but a significant percentage will. Cancers with specific mutations usually have a more predictable response to certain drug treatments when compared to cancers without these mutations[2]. These cancers respond well to targeted drugs or targeted therapy.
In a person diagnosed with breast cancer, genetic information is acquired via gene expression tests. Gene expression is the body’s process to make specific proteins from the information contained within genes. Different tissues express different sets of genes based on their function in the body. Within the cell, information from genes is used to make a template for building ribonucleic acid (RNA). This RNA is processed to create the protein that is required by the cell.
Gene expression tests[3] evaluate the RNA in a person’s tissue sample to determine which genes are actively making proteins within the tumour. This information can then be used to predict the disease outcome by estimating the risk of recurrence of the cancer[4]. They also show how responsive the cancer will be to various treatments.
These tests are relatively new, but their use is increasing as they become more affordable and available. Their use is aimed at ultimately developing a personalised approach to patient care and breast cancer therapy. In our breast centre, molecular genetic profiling and testing has been used for more than 15 years. The clinical progress of more than 300 patients has been documented. All of the patients had a histopathological (microscopic examination of the tissue to study the manifestations of disease) confirmation of an early breast cancer (the tumour was less than 5cm across and had spread to a maximum of three axillary lymph nodes).
Usually, with patients of this nature, chemotherapy is recommended. At our breast centre, in these patients, chemotherapy was only recommended if the molecular genetic profile indicated a high risk of relapse. Chemotherapy was not recommended if the molecular genetic profile indicated a low risk of relapse. Each patient was consulted by a team consisting of a surgical, medical and radiation oncologist. Once the decision on further treatment was taken, established protocols were followed.
These patients have been monitored and followed up with for over a decade to determine whether the individual treatment plan, based on the genetic markers in the tumour, has resulted in a better outcome than standard treatment.
Out of more than 300 patients, half of who were low risk, based on the outcome of the molecular genetic profiling, have all survived without relapse despite not having had chemotherapy. Out of the high-risk group, despite receiving chemotherapy, three patients have relapsed. This indicates that the risk assessment with molecular genetic profiling was accurate.
The major outcome was that more than half of the patients who ordinarily would have received chemotherapy could safely be spared it and all the feared side effects without compromising the outcome. In addition, a few patients who ordinarily would not have received chemotherapy were identified to have high risk tumours and underwent chemotherapy – a potentially life-saving addition to their treatment.
These outcomes are in line with experience at some of the best cancer centres globally. It confirms that molecular genetic testing can reduce the number of individuals who undergo chemotherapy and save lives due to a more aggressive treatment regimen being prescribed for individuals who, at first diagnosis, would appear to be low risk. It gives medical professionals a new level of information from which to determine prognosis and treatment options and, ultimately, allows for a more individualised approach to cancer prognosis and treatment.
A recent article by the BBC[5] reported that “an ultra-sensitive new blood test can predict if breast cancer will return years before the disease shows up on scans,” as it “picks up traces of a tumour’s DNA before a full relapse and was found to be 100% accurate at predicting which patients would see their cancer return.” It is still in its early stages.
Updated guidelines by The American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO), as published by the ‘Journal of Clinical Oncology’[6] in January 2024, now recommend BRCA1 and BRCA2 testing for anyone newly diagnosed with breast cancer (age 65 or younger). BRCA tests look for changes to DNA (genetic material inside cells) that can increase the patient’s risk.
These types of advances in research and medical science continue to shine a light and bring hope to all who are or may be affected by this disease.
[1] E. R. Malone, M. Oliva, P. J. B. Sabatini, T. L. Stockley, and L. L. Siu, “Molecular profiling for precision cancer therapies,” Genome Med., vol. 12, no. 1, pp. 1–19, 2020.
[2] https://labtestsonline.org/tests/genetic-tests-targeted-cancer-therapy
[3] https://labtestsonline.org/tests/breast-cancer-gene-expression-tests
[4] https://labtestsonline.org/tests/her2
[5] Breast cancer: New blood test can predict return, researchers say (bbc.com)
[6] Study: New Genetic Testing Guidelines Include More People (breastcancer.org)
