Biomarkers

By Ashley Pattammady and Violet Reges

Biomarkers are biological molecules that can be found in blood, urine, or other body fluids and can indicate signs of disease or abnormalities. In cancer treatment, biomarker testing is used to help find a treatment, therapy, and/or clinical trial that can be effective in treating cancers. When detecting cancer, biomarkers can be applied in six different settings. These settings are risk assessment, screening and detection, diagnosis, prognosis, prediction, and monitoring (Diagnostics, 2016). To further under stand biomarkers, this report highlights literature research on major breast cancer biomarkers and their significance in breast cancer studies and treatment.During our research, some notable breast cancer biomarkers included established biomarkers and emerging biomarkers. Some established biomarkers included Estrogen receptor (ER), ProgesteroneReceptor (PgR), and HER2. Estrogen receptor (ER) is known as a biomarker that predicts how specific breast cancer treatments will respond to chemotherapy. Progesterone Receptor (PgR) was found to be dependent on the presence of estrogen receptor (ER). Both estrogen and progesterone receptors are crucial in understanding hormone status in breast cancer and the stimulation in breast cancer growth. HER2 is a receptor that controls cell growth and repair. Patients with over expressed presence of HER2 are likelier to relapse and have a shorter lifespan (Wiegel, 2010).Some emerging biomarkers we learned included the Ki67, Cyclin D1, and Cyclin E genes. TheCyclin D1 gene is involved in the pathogenesis of cancers, and is especially prominent in breast cancer as it is able to determine uncontrolled cell proliferation caused during the cell cycle. And so, this gene is important in understanding how fast breast cancer tumors grow (Montalto, 2020). In fact, it was reported that Cyclin D1 is over expressed in the mRNA and protein in over 50% of breast cancer cases, showing that it’s a crucial biomarker to study about (Wiegel).Likewise, Cyclin E works similarly to Cyclin D1 as it is a positive regulator of cell cycle transition with peak levels of protein expression. It was found that Cyclin E gene amplification has been detected in several breast cancer cell lines, and there is strong evidence that Cyclin E plays a role in tumorigenesis (Wiegel).The emerging biomarker, the Ki67 gene, was specifically chosen as the gene of interest for more in depth research and understanding. We discovered that the Ki67 biomarker is known as a cell proliferation marker in breast cancer (Nielsen etal., 2021). The Ki67 gene is recently gaining interest in research pertaining to predicting patient response to chemotherapy. And so, we reviewed a clinical study evaluating the prognostic significance of Ki67 before and after neo adjuvant chemotherapy for breast cancer. From the study, Ki67 alone was found to be a strong predictor of long-term outcome and for recurrence-free and overall survival in breast cancer. This means that the Ki67 gene can suggest the likelihood of breast cancer recurrence after a treatment such as chemotherapy is completed. In addition to the Ki67 genes potential in predictive measures, a higher pretreatment score can influence a good chance to achieve pCR and can also encourage predictions in patient outcomes in the long-term (Joneset al.2009). pCR in the context of breast cancer is a good sign because it indicates that the presence of all invasive cancer in the breast has disappeared. However, although there is much positive feedback for breast cancer treatment in the presence of the Ki67 gene, we recognize it is still an emerging biomarker that needs further studies and research.To conclude, from our research we were able to learn what biomarkers are, several types of biomarkers prominent in breast cancer research, and overall an appreciation of current literature and how such research plays a crucial role in treating breast cancer.

Glossary

Risk assessment:to conduct screenings in order to detect cancer at an early stage.

Screening and detection:to indicate presence of disease, biomarkers for screening/detection are real-time indicators of cancer presence.

Diagnosis:definitive diagnosis to determine origin of a tumor.

Prognosis/Prognostic:a type of classification fora biomarker which can inform the patient's likely outcome of a cancer treatment and/or disease. Also, suggest the likely outcome of a disease in an individual.

Prediction:to predict patient response to treatments and determine optimal drug dose.

Monitoring: to monitor a patient's cancer recurrence after treatment and therapeutic response.Pathogenesis:the process by which a disease or disorder develops

Cell Proliferation:a biological process that indicates an increase in cell number and tissue growth

Tumorigenesis:the production or formation of a tumor or tumors.

Neo adjuvant chemotherapy:the administration of therapeutic agents before a main treatment. (ex.chemotherapy, radiation, hormone therapy)

pCR:Pathological complete response (pCR) is a disappearance of all invasive cancer in the breast after completion of neo adjuvant chemotherapy

Works CitedDiagnostics, P. (2016, October 14).6 types of biomarkersin cancer detection. ProvistaDiagnostics. Retrieved November 27, 2021, fromhttps://www.provistadx.com/blog/6-types-of-biomarkers-in-cancer-detection.Jones, R. L., Salter, J., A’Hern, R., Nerurkar, A., Parton, M., Reis-Filho, J. S., ... & Dowsett, M. (2009).The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer.Breast cancer research and treatment,116(1), 53-68.Montalto, F. I., & De Amicis, F. (2020). Cyclin D1 in Cancer: A Molecular Connection for CellCycle Control, Adhesion and Invasion in Tumor and Stroma. Cells, 9(12), 2648.https://doi.org/10.3390/cells9122648Nielsen, T. O., Leung, S. C. Y., Rimm, D. L., Dodson, A., Acs, B., Badve, S., ... & Hayes, D. F.(2021). Assessment of Ki67 in breast cancer: updated recommendations from the internationalKi67 in breast cancer working group.JNCI: Journalof the National Cancer Institute,113(7),808-819.Weigel, M. T., & Dowsett, M. (2010). Current and emerging biomarkers in breast cancer:prognosis and prediction. Endocrine-related cancer, 17(4), R245-R262.