JAMA oncology
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Triple-negative breast cancer (TNBC) classified by transcriptional profiling as the mesenchymal subtype frequently harbors aberrations in the phosphoinositide 3-kinase (PI3K) pathway, raising the possibility of targeting this pathway to enhance chemotherapy response. Up to 30% of mesenchymal TNBC can be classified histologically as metaplastic breast cancer, a chemorefractory group of tumors with a mixture of epithelial and mesenchymal components identifiable by light microscopy. While assays to identify mesenchymal TNBC are under development, metaplastic breast cancer serves as a clinically identifiable surrogate to evaluate potential regimens for mesenchymal TNBC. ⋯ Using metaplastic TNBC as a surrogate for mesenchymal TNBC, DAT and DAE had notable activity in mesenchymal TNBC. Objective response was limited to patients with PI3K pathway aberration. A randomized trial should be performed to test DAT and DAE for metaplastic TNBC, as well as nonmetaplastic, mesenchymal TNBC, especially when PI3K pathway aberrations are identified.
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Clinical Trial
MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma.
Current recommendations for patients with cirrhosis are to undergo surveillance for hepatocellular carcinoma (HCC) with ultrasonography (US) every 6 months. However, the sensitivity of US screening to detect early-stage HCC is suboptimal. Magnetic resonance imaging (MRI) with liver-specific contrast may detect additional HCCs missed by US in high-risk patients with cirrhosis. ⋯ In patients with cirrhosis at high-risk of HCC, screening that used MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. With MRI screening, most of the cancers detected were at very early stage, which was associated with a high chance of curative treatments and favorable survival of patients. Whether surveillance with MRI would reduce mortality from HCC in high-risk patients requires further investigation.
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Randomized Controlled Trial
Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial.
KRAS mutations are common in pancreatic cancer, but directly targeting the KRAS protein has thus far been unsuccessful. The aim of this trial was to block the MEK and PI3K/AKT pathways downstream of the KRAS protein as an alternate treatment strategy to slow cancer growth and prolong survival. This was the first cooperative group trial to evaluate this strategy using molecularly targeted oral combination therapy for the treatment of chemotherapy-refractory pancreatic cancer. ⋯ Dual targeting of the MEK and PI3K/AKT pathways downstream of KRAS by selumetinib plus MK-2206 did not improve overall survival in patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed. This was the first randomized prospective evaluation of mFOLFOX in the US population that showed comparable results to CONKO-003 and PANCREOX.
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Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. ⋯ As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.