Clinical implications of the intrinsic molecular subtypes of breast cancer

Abstract

Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

Emerging functional roles of nuclear receptors in breast cancer

“…Breast cancer is a heterogeneous disease encompassing multiple subtypes with distinct molecular profiles, therapeutic response and clinical outcomes (Prat et al 2015). Several NRs have been shown to either act co-operatively with ESR1 and/or have differential 789-799, copyright (2006), with permission from Elsevier).…”

Critical Role of a Novel Biological Marker GALNT14 Expression in Different Cancer Types

“…Although breast cancer mortality is reduced by current treatments, more than 450,000 deaths are expected each year due to breast cancer [8]. Tumor metastasis of breast cancer stil significantly reduces survival [9].…”

Molecular genetic markers of breast cancer

“…Для преодоления этой проблемы и более точной классификации, основанной на экспрессии генов, разрабатываются подходы, позволяющие повысить надежность отнесения опухоли к тому или иному типу с использованием наиболее распространенной тест-системы РАМ50 [16].…”