Journal ArticleDOI
Challenges translating breast cancer gene signatures into the clinic
TLDR
The hurdles in the development and validation of molecular classification systems, and prognostic and predictive signatures based on microarray gene-expression profiling are discussed and it is suggested that similar challenges are likely to be encountered in translating next-generation sequencing data into clinically useful information.Abstract:
The advent of microarray-based gene-expression profiling a decade ago raised high expectations for rapid advances in breast cancer classification, prognostication and prediction. Despite the development of molecular classifications, and prognostic and predictive gene-expression signatures, microarray-based studies have not yielded definitive answers to many of the questions that remain germane for the successful implementation of personalized medicine. There are a lack of robust signatures to predict benefit from specific therapeutic agents and it is still not possible to predict prognosis or chemotherapy treatment response in specific disease subsets accurately, such as triple-negative breast cancer. We discuss the hurdles in the development and validation of molecular classification systems, and prognostic and predictive signatures based on microarray gene-expression profiling. We suggest that similar challenges are likely to be encountered in translating next-generation sequencing data into clinically useful information. Finally we highlight strategies for the development of clinically useful molecular predictors in the future.read more
Citations
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Journal ArticleDOI
Gene expression profiling in breast cancer: classification, prognostication, and prediction
TL;DR: In this paper, the conceptual effect and potential clinical use of the molecular classification of breast cancer, and discuss prognostic and predictive multigene predictors are discussed, and a molecular classification system and prognostic multi-genene classifiers based on microarrays or derivative technologies have been developed and are being tested in randomised clinical trials and incorporated into clinical practice.
Gene expression profi ling in breast cancer: classifi cation, prognostication, and prediction
TL;DR: In this paper, the conceptual effect and potential clinical use of the molecular classification of breast cancer, and discuss prognostic and predictive multigene predictors are discussed, and a molecular classification system and prognostic multi-genene classifiers based on microarrays or derivative technologies have been developed and are being tested in randomised clinical trials and incorporated into clinical practice.
Journal ArticleDOI
Intratumor Heterogeneity: Seeing the Wood for the Trees
Timothy A. Yap,Marco Gerlinger,Marco Gerlinger,P. Andrew Futreal,Lajos Pusztai,Charles Swanton,Charles Swanton +6 more
TL;DR: Envisaging tumor growth as a Darwinian tree with the trunk representing ubiquitous mutations and the branches representing heterogeneous mutations may help in drug discovery and the development of predictive biomarkers of drug response.
Journal ArticleDOI
Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer.
Kamal S Saini,Kamal S Saini,Sherene Loi,Evandro de Azambuja,Otto Metzger-Filho,Monika Lamba Saini,Michail Ignatiadis,Janet Dancey,Martine Piccart-Gebhart,Martine Piccart-Gebhart +9 more
TL;DR: A review of the current relevant pre-clinical and clinical data is presented and the rationale for dual inhibition of these pathways in the treatment of BC patients is discussed.
Journal ArticleDOI
Circulating tumour cells and cell-free DNA as tools for managing breast cancer.
Leticia De Mattos-Arruda,Javier Cortes,Libero Santarpia,Ana Vivancos,Josep Tabernero,Jorge S. Reis-Filho,Joan Seoane +6 more
TL;DR: The current status of blood-born biomarkers as surrogates for tissue-based biomarkers, and their burgeoning impact on the management of patients with breast cancer are discussed.
References
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Journal ArticleDOI
A robust classifier of high predictive value to identify good prognosis patients in ER-negative breast cancer.
TL;DR: This seven-gene classifier could be used in a polymerase chain reaction-based clinical assay to identify ER- patients with a good prognosis, who may therefore benefit from less aggressive treatment regimens.
Journal ArticleDOI
Molecular profiling currently offers no more than tumour morphology and basic immunohistochemistry.
TL;DR: Despite the huge amount of resources allocated to translational research endeavours, only three predictive markers are utilised to define the therapy of breast cancer patients: oestrogen receptor and progesterone receptor (PR), the predictive markers of response to endocrine therapy, and human epidermal growth factor receptor 2 (HER2), the molecular target of trastuzumab and lapatinib.
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Breast cancer assessment tools and optimizing adjuvant therapy
TL;DR: Recommendation of systemic adjuvant therapy and choice of optimal agents for early-stage breast cancer remains a challenge and the presence of drug targets and targetable signaling pathways, rather than molecularly defined subgroups, may ultimately drive treatment decisions.
Journal ArticleDOI
Molecular Profiling: Moving Away from Tumor Philately
TL;DR: On the wave of recent scientific advances and clinical findings, new cutting-edge technologies are poised to deliver an array of diverse molecular data that are expected to dramatically alter breast cancer diagnosis and treatment.
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