Biomarkers for the clinical management of breast cancer: International perspective

Abstract

The higher incidence of breast cancer in developed countries has been tempered by reductions in mortality, largely attributable to mammographic screening programmes and advances in adjuvant therapy. Optimal systemic management requires consideration of clinical, pathological and biological parameters. Oestrogen receptor alpha (ERa), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) are established biomarkers evaluated at diagnosis, which identify cardinal subtypes of breast cancer. Their prognostic and predictive utility effectively guides systemic treatment with endocrine, anti-HER2 and chemotherapy. Hence, accurate and reliable determination remains of paramount importance. However, the goals of personalized medicine and targeted therapies demand further information regarding residual risk and potential benefit of additional treatments in specific circumstances. The need for biomarkers which are fit for purpose, and the demands placed upon them, is therefore expected to increase. Technological advances, in particular high-throughput global gene expression profiling, have generated multi-gene signatures providing further prognostic and predictive information. The rational integration of routinely evaluated clinico-pathological parameters with key indicators of biological activity, such as proliferation markers, also provides a ready opportunity to improve the information available to guide systemic therapy decisions. The additional value of such information and its proper place in patient management is currently under evaluation in prospective clinical trials. Expanding the utility of biomarkers to lower resource settings requires an emphasis on cost effectiveness, quality assurance and possible international variations in tumor biology; the potential for improved clinical outcomes should be justified against logistical and economic considerations.

Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD

“…Incidence rates are high in developed regions of the world (except Japan) and low in most of the developing regions [1]. The higher incidence of breast cancer in developed countries has been tempered by reductions in mortality, largely attributable to mammographic screening programs and advances in adjuvant therapy [2]. However, mammography screening has moderate sensitivity and specificity and a low positive-predictive value in younger women.…”

“…The established biomarkers include tissue markers, such as estrogen and progesterone receptors and the human epidermal growth factor receptor 2 (HER2), and circulating markers, such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3). Circulating tumor cells are emerging biomarkers that have potential to become clinically useful [2,7].…”

Could the Breast Prognostic Biomarker Status Change During Disease Progression? An Immunohistochemical Comparison between Primary Tumors and Synchronous Nodal Metastasis

“…Estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) have been established as principal biomarkers for breast cancer management; their evaluation has become a routine step before starting the endocrine and anti HER2 and chemotherapy (Patani et al, 2013).…”

“…Thus, the introduction of hormonal therapy and selective targeted therapy, especially tamoxifen and trastuzumab, has significantly changed breast cancer outcome worldwide, and thus the current therapeutic strategies for management of cancer breast have become dependent on the accurate immunohistochemical (IHC) determination of hormone receptor status and Her2 status in order to determine the clinical utility and effectiveness of hormone-directed therapies and Herceptin (Jabbour et al, 2012) and (Patani et al, 2013) Although they are now routinely evaluated, the endocrine markers and Her2 have proved to be potentially heterogeneous in their expression, even within the same tumor (Patani et al, 2013) , the fact that raised several questions regarding the potential or possible phenotypic switch in hormonal receptors and Her-2 expression between the primary and nodal/metastatic site; whether patients should be tested for ER, PR, and Her-2/neu expression in the nodal metastasis, and whether this will carry different prognostic message or not, remains elusive (Jabbour et al, 2012) (Arapantoni-Dadioti et al, 2012).…”

Clinical potential of the mTOR effectors S6K1, S6K2 and 4EBP1 in breast cancer

“…Based on genome-wide gene expression data, several multigene assays have been developed and shown able to predict outcome in certain patient groups [17]. The Real-Time polymerase chain reaction (PCR) based Oncotype Dx profile involving 21 genes, can be used to predict overall survival among patients with node-negative ER-positive breast cancers treated with tamoxifen.…”