Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Jul 2015
ReviewA decision support framework for genomically informed investigational cancer therapy.
Rapidly improving understanding of molecular oncology, emerging novel therapeutics, and increasingly available and affordable next-generation sequencing have created an opportunity for delivering genomically informed personalized cancer therapy. However, to implement genomically informed therapy requires that a clinician interpret the patient's molecular profile, including molecular characterization of the tumor and the patient's germline DNA. In this Commentary, we review existing data and tools for precision oncology and present a framework for reviewing the available biomedical literature on therapeutic implications of genomic alterations. ⋯ For these genomic alterations in other diseases and for other genomic alterations, the clinical data are either absent or insufficient to support routine clinical implementation of biomarker-based therapy. However, there is great interest in optimally matching patients to early-phase clinical trials. Thus, we need accessible, comprehensive, and frequently updated knowledge bases that describe genomic changes and their clinical implications, as well as continued education of clinicians and patients.
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J. Natl. Cancer Inst. · Jul 2015
Comparative StudyPractical problems with clinical guidelines for breast cancer prevention based on remaining lifetime risk.
Clinical guidelines for breast cancer chemoprevention and MRI screening involve estimates of remaining lifetime risk (RLR); in the United States, women with an RLR of 20% or higher meet "high-risk" criteria for MRI screening. ⋯ RLR-based guidelines for high-risk women are limited by discordance between commonly used risk models. Guidelines based on short-term risks would be more useful, as models are generally developed and validated under a short fixed time horizon (≤10 years).
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J. Natl. Cancer Inst. · Jul 2015
Benefits and harms of mammography screening after age 74 years: model estimates of overdiagnosis.
The aim of this study was to quantify the benefits and harms of mammography screening after age 74 years, focusing on the amount of overdiagnosis of invasive breast cancer and ductal carcinoma in situ (DCIS). ⋯ The balance between screening benefits and harms becomes less favorable after age 74 years. At age 90 years, harms outweigh benefits, largely as a consequence of overdiagnosis. This age was the same across the three models, despite important model differences in assumptions on DCIS.
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Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. ⋯ PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans.