Gene-Expression-Based Predictors for Breast Cancer

Abstract

An important and often complicated management decision in early stage hormone receptor (HR)-positive breast cancer relates to the use of adjuvant systemic chemotherapy. Although traditional clinicopathologic markers exist, tremendous progress has been achieved in the field of predictive biomarkers and genomics with both prognostic and predictive capabilities to identify patients who will potentially benefit from additional therapy. The use of these genomic tests in the neoadjuvant setting is also being studied and may lead to these tests providing clinical benefit even earlier in the disease course. Landmark articles published in the last few years have expanded our knowledge of breast cancer genomics to an unprecedented level, and mutational analysis via next-generation sequencing methods allows the identification of molecular targets for novel targeted therapeutic agents and clinical trials testing efficacy of targeted therapies, such as PI3K inhibitors, in addition to endocrine therapy for HR-positive breast cancer, are ongoing. We provide an in-depth review on the role of gene expression-based predictors in early stage breast cancer and an overview of future directions, including next-generation sequencing. Over the coming years, we anticipate a significant increase in utilization of genomic-based predictors for individualized selection and duration of endocrine therapy with and without genotype-driven targeted therapy, and a major decrease in the use of chemotherapy, possibly even leading to a chemotherapy-free road for early stage HR-positive breast cancer.

Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer

“…Breast cancer is at the forefront of precision medicine, a paradigm that uses individual variation in genes, environment, and lifestyle to improve disease prevention, diagnosis and treatment [1][2][3]. With advances in next generation sequencing, the application of this paradigm in breast cancer has progressed from identification of hormone receptor and HER-2 expression to genomic profiling of tumors to assess a range of gene expression levels and identify mutations in specific genes that may drive tumor progression and offer targets for therapeutic intervention [4][5][6].…”

‘Omics Approaches to Explore the Breast Cancer Landscape

“…With 'omics technologies applied to patient samples becoming robust, our understanding of the mechanisms driving breast cancer and the discovery of novel biomarkers and therapeutic targets have improved significantly over the last few years (Chakraborty et al, 2018;Manem et al, 2018). For instance, the use of molecular assays, including OncotypeDx and MammaPrint in the clinic is based on advancements in genomic technologies (Gupta et al, 2015;Vieira and Schmitt, 2018). Transparent sharing of 'omics data in databases like COSMIC (Forbes et al, 2008), PRIDE (Jones et al, 2006) and others ( Table 2) will allow unbiased analysis of available data by different groups to find previously unnoticed potential genes or proteins of interest as biomarkers or therapeutic targets.…”

Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin

“…Chemotherapy with cytotoxic/cytostatic agents may be inefficient. Thus, the search for more effective treatments has become one of the important targets in the study of pharmacogenetics and pharmacogenomics in cancer [4, 5]. …”

“…This phenomenon causes greater toxicity of the agents in tissues such as mucosae and cells of the immunological system since they are capable of accumulating more damage. Another important aspect is the ability of the neoplastic cell to undergo mutations that can trigger resistance to chemotherapeutics, thus reducing therapeutic efficacy [4, 5]. This condition is associated with the fact that cell cycles of tumor cells occur within a shorter period of time and more frequently [5].…”