Incorporating Genomics into Breast Cancer Clinical Trials and Care

Tabchy, Adel; Cynthia, X.; Bose, Ron; Ellis, Matthew J.

doi:10.1158/1078-0432.ccr-13-0837

Cited by 14 publications

(10 citation statements)

References 41 publications

(60 reference statements)

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“…Prospective trials to study the role of PI3K inhibitors in patients with breast cancer brain metastases are under consideration. As highlighted by Tabchy and colleagues in this CCR Focus section, increasingly, it may be possible to analyze molecular alterations in blood (i.e., liquid biopsy), including for tumor PIK3CA mutations and other alterations (80). In the setting of brain metastases, these approaches may be particularly valuable given the difficulty in directly accessing CNS tumor tissue.…”

Section: Other Molecular Targetsmentioning

confidence: 99%

CNS Metastases in Breast Cancer: Old Challenge, New Frontiers

Lin

Amiri‐Kordestani

Palmieri

et al. 2013

Clinical Cancer Research

238

208

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Despite major therapeutic advances in the management of patients with breast cancer, central nervous system (CNS) metastases remain an intractable problem, particularly in patients with metastatic HER2-positive and triple-negative breast cancer. As systemic therapies to treat extracranial disease improve, some patients are surviving longer, and the frequency of CNS involvement seems to be increasing. Furthermore, in the early-stage setting, the CNS remains a potential sanctuary site for relapse. This review highlights advances in the development of biologically relevant preclinical models, including the development of brain-tropic cell lines for testing of agents to prevent and treat brain metastases, and summarizes our current understanding of the biology of CNS relapse. From a clinical perspective, a variety of therapeutic approaches are discussed, including methods to improve drug delivery, novel cytotoxic agents, and targeted therapies. Challenges in current trial design and endpoints are reviewed. Finally, we discuss promising new directions, including novel trial designs, correlative imaging techniques, and enhanced translational opportunities. Clin Cancer Res; 19(23); 6404-18. Ó2013 AACR. Disclosure of Potential Conflicts of InterestN.U. Lin has received commercial research grants from GlaxoSmithKline, Genentech, Array, and Novartis. N.U. Liu is a consultant/advisory board member for Novartis, GlaxoSmithKline, to-BBB, and Genentech. P.S. Steeg has received commercial research grants from GlaxoSmithKline and Sanofi. No potential conflicts of interest were disclosed by the other authors. CME Staff Planners' DisclosuresThe members of the planning committee have no real or apparent conflict of interest to disclose. Learning Objective(s)Upon completion of this activity, the participant should have a better understanding of brain metastases in different subtypes of breast cancer, the development of preclinical models, and the novel systemic strategies for breast cancer brain metastasis.

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Section: Other Molecular Targetsmentioning

confidence: 99%

CNS Metastases in Breast Cancer: Old Challenge, New Frontiers

Lin

Amiri‐Kordestani

Palmieri

et al. 2013

Clinical Cancer Research

238

208

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“…An example of adaptive biomarker trial design is the ongoing I-SPY 2 neoadjuvant trial (44). Genome-driven neoadjuvant trials are also reviewed in this CCR Focus series (45).…”

Section: Key Considerations For Neoadjuvant Drug Developmentmentioning

confidence: 99%

Neoadjuvant Therapy as a Platform for Drug Development and Approval in Breast Cancer

Bardia

Baselga

2013

Clinical Cancer Research

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The traditional drug development process in breast cancer based on large phase III studies has serious limitations and needs a major overhaul. Searching for new approaches, the testing of novel agents in the preoperative (neoadjuvant) setting approach offers a potentially rapid and efficient strategy for drug development utilizing pathologic complete response (path CR), a surrogate marker for survival, as the primary endpoint. In addition, neoadjuvant studies allow the assessment of drug effects on the target (pharmacodynamic response) and the development of predictive biomarkers of response. Molecular profiling of the residual tumor in the surgical specimen may also provide insights into actionable mechanisms of resistance. Recognizing the potential of neoadjuvant trials for drug development, the U.S. Food and Drug Administration (FDA) recently announced consideration of neoadjuvant trials for accelerated drug approval in early breast cancer, particularly for tumors with high risk of recurrence and unfavorable prognosis, and provided accelerated approval to neoadjuvant pertuzumab in September 2013. The FDA has emphasized that while improvement in path CR could be utilized for "accelerated" approval, improvement in survival will still need to be demonstrated for "regular" approval. Key considerations in conduct of such neoadjuvant drug development trials include (i) study design such as utilization of biomarker stratified design to evaluate a biomarker that could enrich response, (ii) definition of path CR, (iii) distribution of factors that influence path CR between the treatment arms, (iv) prespecified plan for follow-up to obtain data on survival, and (v) safety as it involves a patient population with curable disease. In the years to come, we anticipate an increase in the number of neoadjuvant trials testing novel therapies that hopefully will open a new path in bringing efficacious new therapies to patients with breast cancer.

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“…Delivering recommendations in a clinical setting requires fast analysis of genome-scale big data in a reliable manner. This field is still in a nascent stage with applications in specific focus areas, such as cancer [131][132][133][134], because of cost, time, and labor intensive nature of analyzing this big data problem.…”

Section: Big Data Applications In Genomicsmentioning

confidence: 99%

Big Data Analytics for Healthcare

Raj

Raman

Nagaraj

et al. 2015

Computer Communications and Networks

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The rapidly expanding field of big data analytics has started to play a pivotal role in the evolution of healthcare practices and research. It has provided tools to accumulate, manage, analyze, and assimilate large volumes of disparate, structured, and unstructured data produced by current healthcare systems. Big data analytics has been recently applied towards aiding the process of care delivery and disease exploration. However, the adoption rate and research development in this space is still hindered by some fundamental problems inherent within the big data paradigm. In this paper, we discuss some of these major challenges with a focus on three upcoming and promising areas of medical research: image, signal, and genomics based analytics. Recent research which targets utilization of large volumes of medical data while combining multimodal data from disparate sources is discussed. Potential areas of research within this field which have the ability to provide meaningful impact on healthcare delivery are also examined.

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Incorporating Genomics into Breast Cancer Clinical Trials and Care

Cited by 14 publications

References 41 publications

CNS Metastases in Breast Cancer: Old Challenge, New Frontiers

CNS Metastases in Breast Cancer: Old Challenge, New Frontiers

Neoadjuvant Therapy as a Platform for Drug Development and Approval in Breast Cancer

Big Data Analytics for Healthcare

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