Background: Histologically similar tumors may have different prognoses and responses to treatment. These differences are due to molecular differences. Hence, in this review, the biological interaction of breast cancer in several different areas is discussed. In addition, the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from a biological perspective and current global advances in these areas are addressed. 

Objective: This review provides the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from the biological perspective and current global advances in these areas. 

Methods: PubMed, Scopus, and Google Scholar were searched comprehensively with combinations of the following keywords: “breast cancer,” “biological markers,” and “clinical.” The definition of breast cancer, diagnostic methods, biological markers, and available treatment approaches were extracted from the literature.

Results: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67 are the most well-known biological markers that have important roles in prognosis and response to therapeutic methods. Some studies showed the response of ER-positive and PR-negative tumors to anti-estrogenic treatment to be lower than ER-positive and PR-positive tumors. Patients with high expression of HER-2 and Ki-67 had a poor prognosis. In addition, recent investigations indicated the roles of new biomarkers, such as VEGF, IGF, P53 and P21, which are associated with many factors, such as age, race, and histological features.

Conclusion: The objective of scientists, from establishing a relationship between cancer biology infrastructures with clinical manifestations, is to find new ways of prevention and progression inhibition and then possible introduction of less dangerous and better treatments to resolve this dilemma of human society.


Keywords: Estrogen receptor, progesterone receptor, biological markers, breast cancer, human epidermal growth factor receptor-2
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