Use of standard markers and incorporation of molecular markers into breast cancer therapy

Abstract

Breast cancer is a heterogeneous disease of different subtypes on the molecular, histopathological, and clinical level. Genomic profiling techniques have led to several prognostic and predictive gene signatures of breast cancer that may further refine outcome prediction, especially in clinically equivocal situations. In particular, the predictive value of today's most important therapeutic targets, ER and HER2, are strongly influenced by the proliferative status of the tumor. Genomic assays are generally performed in a centralized manner, whereas routine pathological evaluation is mostly done on a decentralized basis, making the comparison of these methods difficult. Thus, there remains considerable uncertainty about the use of the new molecular markers in routine clinical decision making and their role in patient selection or stratification for future clinical trials. To address this concern, a group of representatives from breast cancer research groups in the areas of breast pathology, genomic profiling, and clinical trials critically reviewed all available data. Consensus recommendations are made on the practical use of molecular markers in breast cancer management and their incorporation into future clinical trials. Cancer 2011. © 2010 American Cancer Society.

Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

“…1,5,18,22 However, the biological significance and internal interactions of these three molecules should be investigated further to determine their heterogeneity and guide treatment in the complexities of the clinical setting, which is one of the key issues for personalized care of breast cancer. 1,3,14,23 In this study, we investigated these relationships based on quantitative determination of HER2 and hormone receptor status by QD nanotechnology, and found them to be consistent with our own previous results 12 and other reports.…”

“…1,[6][7][8][9] For example, about one third of hormone receptor-positive patients benefit little from endocrine therapy according to current criteria. 1,5,10 Further, some hormone receptor-positive patients with a potentially better prognosis are subjected to intensive chemotherapy but suffer from toxicity (overtreatment), while other patients at high risk of recurrence receive inadequate treatment, leading to compromised efficacy (undertreatment). Another convincing example is the limited utility of the current criteria in guiding molecular-targeted HER2 therapy.…”

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

“…Although longitudinal declines in lung function (11)(12)(13)(14), extensive fibrosis, and honeycombing on highresolution CT imaging are associated with worsening mortality, they give little information on pathogenesis or likely response to therapy. Molecular and histopathologic stratification is well established in cancer studies (15)(16)(17), but attempts to stratify IPF on the basis of histopathologic or molecular phenotyping have been unconvincing (18,19). Furthermore, the high mortality rate associated with videoassisted thoracoscopic surgical biopsy and the lack of longitudinal sample collection makes histopathologic phenotyping in IPF problematic.…”

High-Throughput Gene Expression and Mutation Profiling: Current Methods and Future Perspectives

“…The basic classification of these intrinsic subtypes encompasses the estrogen receptor (ER)-negative ‘basal-like' and ‘HER2-like' subgroups as well as two different ER-positive ‘luminal A' and ‘luminal B' subtypes (table 1). The intrinsic subtypes differ both in their prognosis [12] and their response to systemic therapies [5,6,7]. The basal-like and HER2-like subtypes, for example, display a poor prognosis but an increased response to chemotherapy [13,14,15].…”

“…In this review we focus on gene expression profiling by microarray methods and mutation profiling through next generation sequencing (NGS). Since a large number of reviews on gene expression signatures in breast cancer and the corresponding genomic tests have recently appeared [4,5,6,7], the emphasis here will be on the newer developments in cancer genome sequencing.…”