in 69 patients treated with metronomic capecitabine plus cyclophosphamide and i.v. bevacizumab for metastatic breast cancer. In the paper byWenzel et al., higher MCV penlac values were seen in patients with tumor remission or stable disease rather than in patients with tumor progression, but the difference was not statistically significant. This might be due first of all to the different tumor types and various treatment schedules considered in the paper, as compared to our homogeneous cohort of metastatic breast cancer patients. Secondly, the capecitabine schedule considered in the paperwas the standard one (2500 mg/m2/day for 14 days every 21 days) while in our report it was a metronomic one (1500 mg/day continuously). Further investigations should be performed to assess whether different schedules of capecitabine may result in different duration of inhibition of TS, similarly to the different mechanism of action of i.v. bolus 5-FU and continuous infusion 5-FU.

Given the absence of rest periods during treatment without an opportunity to repair DNA and recover function, the metronomic schedule might exert a permanent inhibition of TS. Cabozantinib TS polymorphism in peripheral blood cells may be used as a surrogate for intratumoral TS. Our finding support the hypothesis that TS inhibition in erythroid precursor cells corresponds with potent TS inhibition in tumor cells. In conclusion, macrocytosis significantly predicted tumor response in patients treated with metronomic capecitabine plus cyclophosphamide and i.v. bevacizumab for metastatic breast cancer.

These findings may be explained through TS inhibition by capecitabine and likely portray macrocytosis as a pharmacodynamic marker of capecitabine efficacy which is associated with clinical outcome. Whether bevacizumab has a role as a concomitant factor determining macrocytosis, similarly to what happens with sunitinib, has to be further purchase mercaptopurine investigated. If confirmed by other studies, our findings may support the role of macrocytosis as an early surrogate marker of response during metronomic treatment with low dose oral capecitabine and cyclophosphamide with or without bevacizumab. In July 2010, a panel of expert pathologists from the European Union and the rest of the world, with extensive experience of human epidermal growth factor receptor 2 (HER2) testing, met to discuss the requirements for accurate HER2 testing and interpretation in gastric cancer. The recommendations generated from this meeting are summarized in this paper and are based on both the key findings from the trastuzumab for GAstric cancer study and the expertise of the authors in HER2 testing for both breast and gastric cancers. The objective of this paper is to provide up-to-date guidance on order mercaptopurine standardizing tissue processing, HER2 testing, and scoring in patients with gastric and gastro–esophageal junction cancer to help ensure accurate selection of patients eligible for treatment with trastuzumab.

These recommendations are intended not only to complement existing recommendations but also to provide more practical guidance on HER2 testing specific for gastric cancer. When recommendations are made in this article they are made by the panel, unless vasculature otherwise stated. It is anticipated that the recommendations will evolve over time as more information.