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Summary – This article talks about the role of precision medicine in upcoming diagnosis and treatments for Breast Cancer, including genetic studies and immunotherapy, which helps us understand the predisposition of this cancer and potential personalized therapy development.
Precision medicine, as the term explains itself, helps in the analysis of a disease at a higher resolution with the help of genome sequencing and other associated technologies to enhance the treatment through improved diagnostic sensitivity and meticulous therapeutics, offering a modern paradigm (1). One of the first areas of medicine to apply precision technology for treatments is Cancer Therapeutics. Several genetic assays and even nongenetic tests accurately assess the causes and risk of progression or recurrence of cancer.
Breast cancer is one of the most prevalent cancers worldwide and the fifth most common cause of death by Cancer. On average, 1 in every 28 Indian women is expected to develop breast cancer at some point during her lifetime. Although, it is more (1 in 22) for urban women than the rural group (1 in 60) (2). Long known causes of breast cancer include family history, where maternal and paternal genetic lineage is essential, hormonal imbalance consequently affecting the menstrual cycle, and one of the most critical, genetic alterations.
According to genetic analysis, rare high penetrance mutations of genes BRCA1 and BRCA2, when inherited, markedly increase the risk of breast-ovarian cancer (3,4). In addition, the mutations in genes CHEK2, PALB2, PTEN and ATM also affect breast cancer risk, which is why other genetic variations must also be explored to deal with this cancer (5). Other factors which might increase the risk of developing breast cancer include excess alcohol consumption, sedentary lifestyle, obesity (particularly in post-menopausal women), exposure to harmful radiation and previous history of breast cancer (3).
Genome-wide association study (GWAS) is a technique in precision medicine that involves scanning of genomes of people from distinct backgrounds to locate specific genetic markers associated with certain diseases. Breast cancer was the first cancer GWAS published, which led to the identification of numerous genetic markers, as mentioned before. In addition, seven novel genetic susceptibility loci were also discovered, 2 of which had a pleiotropic effect on other cancers too, and some were closely associated with oestrogen receptor status [ER+ or ER-] as well (4,5). Another widely used technique, Next-generation sequencing (NGS), which allows simultaneous sequencing of up to millions of DNA fragments, supplemented the findings by adding several rare mutations associated with hereditary breast and ovarian cancer to the list, too (5).
Studying how genetic variants in genes affect drug availability at the target site and drug metabolism, along with drug target proteins and intracellular signalling proteins, play a crucial role in cancer precision medicine. Not only do these studies provide a synopsis of the genetic predisposition of breast cancer in certain people, but these pharmacogenomic insights also help in understanding a patient's sensitivity to a drug resulting in an advancement of prevention and treatment methods (5).
Immunotherapy in breast cancer has drastically evolved in the past decade. Breast cancer was believed to be less immunogenic cancer as compared to other cancers. However, the presence of specific immune cells called tumour infiltrating lymphocytes (TILs) in and around tumours have changed that point of view (6). TILs recognize and target specific proteins on the surface of tumour cells, called neoantigens, which are produced when mutations occur in tumour cell DNA (7).
An NCI study demonstrated complete shrinkage of metastatic breast cancer using personalized immunotherapy this February. By growing reactive TILs, taken from breast cancer patients whose genetic mutations were identified by whole-genome sequencing in the lab and returning them to each patient via intravenous infusion, the researchers were able to display 52-100% shrinkage (7). In addition, recent studies have shown that the presence of TILs within tumours may increase the likelihood of response to chemotherapy as well (6).
Incorporating germline variations to several populations with higher susceptibility to cancer in general and screening of immune cells within tumours could be integrated as a new parameter in therapeutic analysis. It can undoubtedly revolutionize healthcare corresponding to precision medicine. However, due to fragmented data available as of now, intensive research and integrative clinical trials are under progress with the anticipation of improved prototypes for diagnosis and efficient personalized therapies.
References
Ashley, E. (2016). Towards precision medicine. Nature Reviews Genetics, 17(9), 507-522. doi: 10.1038/nrg.2016.86
Statistics of Breast Cancer In India | Cytecare Hospitals. (2019). Retrieved 10 February 2022, from https://cytecare.com/blog/statistics-of-breast-cancer/#:~:text=One%20in%20twenty%2Deight%20Indian,group%20(1%20in%2060).
Ganesh N. Sharma, K. (2010). VARIOUS TYPES AND MANAGEMENT OF BREAST CANCER: AN OVERVIEW. Journal Of Advanced Pharmaceutical Technology & Research, 1(2), 109. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255438/
Garcia-Closas, M., & Chanock, S. (2008). Genetic Susceptibility Loci for Breast Cancer by Estrogen Receptor Status. Clinical Cancer Research, 14(24), 8000-8009. doi: 10.1158/1078-0432.ccr-08-0975
Low, S., Zembutsu, H., & Nakamura, Y. (2017). Breast cancer: The translation of big genomic data to cancer precision medicine. Cancer Science, 109(3), 497-506. doi: 10.1111/cas.13463
Bettaieb, A., Paul, C., Plenchette, S., Shan, J., Chouchane, L., & Ghiringhelli, F. (2017). Precision medicine in breast cancer: reality or utopia?. Journal Of Translational Medicine, 15(1). doi: 10.1186/s12967-017-1239-z
About the Author
Jayanti Chhillar is a final year student, studying B.Sc. (H) Biological Sciences at Sri Venkateswara College, University of Delhi. As a curious kid, she always found intricate cellular and molecular mechanisms and their biochemical pathways fascinating, following which, she aims to pursue higher studies in the field of Molecular Biology and Cancer Therapeutics. Stem cells and Induced Pluripotent Cells is another promising domain of research that she finds extremely captivating and innovative. Inquisitive about, intracellular signalling and functioning, she wants to explore ways by which they can be manipulated for clinical purposes, and consequently develop better medications and contemporary treatments for Cancer.
She loves to interact with like-minded people, understand their perspectives and discuss and learn more about science in general, which is primarily why she’s eagerly looking forward to joining the TSV team.
Outstandingly explained! Very well researched and explained!