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Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen (N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment (N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% (n = 3) and 3.3% (n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% (n = 2) of the resectable patients and 1.6% (n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative.

Background The purpose of this work was to investigate noninvasive early detection of treatment response of breast cancer patients to neoadjuvant chemotherapy (NAC) using chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) at 7 T. Methods CEST images were acquired in 10 tumors of nine breast cancer patients treated with NAC. APT signals in the tumor, before and after the first cycle of NAC, were quantified using a three-pool Lorentzian fit of the z-spectra in the region of interest. The changes in APT were subsequently related to pathological response after surgery defined by the Miller-Payne system. Results Significant differences (P 0.05, Kruskal-Wallis test). Conclusions This preliminary study shows the feasibility of using APT CEST magnetic resonance imaging as a noninvasive biomarker to assess the effect of NAC in an early stage of NAC treatment of breast cancer patients. Trial registration Registration number, NL49333.041.14/NTR4980. Registered on 16 October 2014.

Oral administration of anticancer drugs is most often preferred over intravenous administration, as it is convenient for patients, prevents hospitalisation and reduces costs of the therapy. However, the oral route is often hampered by low oral bioavailability, for instance of the taxanes paclitaxel and docetaxel. Limited oral bioavailability can be due to pharmaceutical as well as pharmacological reasons. Taxanes are poorly water-soluble drugs and do not sufficiently dissolve when administered in their crystalline form. Furthermore, affinity for drug transporters highly expressed in the epithelial layer of the gastro-intestinal tract, such as the drug efflux pump P-glycoprotein (P-gp, ABCB1), and presystemic elimination by the cytochrome P450 (CYP) metabolic enzymes, especially CYP3A4, present in liver and gut wall, further hamper oral application of these important anticancer drugs. Preclinical studies with knockout mice lacking functional Pgp and CYP3A4 metabolic enzymes show a significant increase in the bioavailability of orally applied taxanes. Enhancement of oral bioavailability of both taxanes was shown also in wild-type mice using P-gp and CYP3A4 blockers such as cyclosporine A (CsA) and ritonavir (RTV). Subsequently, in clinical studies enhancement of the oral bioavailability of paclitaxel and docetaxel was established when administered orally in combination with CsA or ritonavir. Initially, in preclinical and clinical studies drinking solutions based on the intravenous formulations were applied for oral administration of taxanes. Because these solutions had several disadvantages, solid pharmaceutical formulations of paclitaxel and docetaxel were developed. Clinical studies with these novel formulations in combination with ritonavir are currently ongoing at our Institute.