BACKGROUND.Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients. The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)‐positive and/or progesterone receptor (PgR)‐positive tumors. This randomized, controlled, phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER‐positive and/or PgR‐positive breast cancer.METHODS.Eligible patients were randomly assigned to receive neoadjuvant anastrozole 1 mg/day (n = 61) or exemestane 25 mg/day (n = 60) for 3 months or doxorubicin 60 mg/m2 with paclitaxel 200 mg/m2 (four 3‐week cycles). Study end points included overall objective response determined by palpation, mammography, and ultrasound, and the number of patients who qualified for breast‐conserving surgery and radiotherapy.RESULTS.Clinical objective response was 64% in the endocrine therapy and chemotherapy treatment groups. Median time to clinical response was 57 and 51 days with aromatase inhibitors and chemotherapy, respectively (P > .05). Rates of pathological complete response (3% vs 6%) and disease progression (9% vs 9%) did not differ significantly in the endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast‐conserving surgery were slightly higher in the endocrine group (33% vs 24%; P = .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade 3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well tolerated. No deaths occurred during the preoperative treatment.CONCLUSIONS.Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well tolerated and resulted in rates similar to chemotherapy in overall objective response and breast‐conserving surgery in postmenopausal women with ER‐positive and/or PgR‐positive tumors. Cancer 2007. © 2007 American Cancer Society.

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The MTD of AZD8931 determined from the 21-day DLT period was 240 mg bid, although more long-term data are needed to confirm a dose of AZD8931 suitable for chronic treatment.

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Purpose: Developing new and efficient approaches for the early diagnosis of colorectal cancer (CRC) is an important issue. Circulating extracellular nanovesicles (ENVs) present a promising class of cancer markers. Cells of well-differentiated adenocarcinomas retain the molecular characteristics of colon epithelial cells, and the ENVs secreted by these cells may have colon-specific surface markers. We hypothesize that an increase in the number of ENVs carrying colon-specific markers could serve as a diagnostic criterion for colorectal cancer. Experimental design: Potential colon-specific markers were selected based on tissue-specific expression profile and cell surface membrane localization data. Plasma was collected from CRC patients (n = 48) and healthy donors (n = 50). The total population of ENVs was isolated with a two-phase polymer system. ENVs derived from colon epithelium cells were isolated using immune-beads with antibodies to colon-specific markers prior to labelling with antibodies against exosomal tetraspanins (CD63 and CD9) and quantification by flow cytometry. Results: The number of ENVs positive for single colon cancer markers was found to be significantly higher in the plasma of CRC patients compared with healthy donors. The efficacy of detection depends on the method of ENV labelling. The diagnostic efficacy was estimated by ROC analysis (the AUC varied between 0.71 and 0.79). The multiplexed isolation of colon-derived ENVs using immune-beads decorated with antibodies against five markers allowed for a further increase in the diagnostic potency of the method (AUC = 0.82). Conclusions: ENVs derived from colon epithelium may serve as markers of differentiated CRC (adenocarcinomas). The composition of ligands used for capturing colon-derived ENVs and their method of labelling are critical for the efficacy of this proposed diagnostic approach.

The development of methods for effective diagnosis and monitoring of colorectal cancer (CRC) treatment is one of the basic scientific problem. The circulating plasma contains extracellular nanovesicles (EVs) secreted mainly by blood and endothelial cells. The minor fraction of plasma EVs is produced by cells of various tissues, including cells of the intestinal epithelium. The biochemical composition of such vesicles should have tissue-specific features. Presented study was aimed to identify surface markers of EVs secreted by intestinal epithelium cells and to assess the possibility of isolating and quantification of such vesicles for the diagnosis of CRC. The cell cultures SW837), plasma of CRC patients and healthy donors were used in the study. The methods of nanoparticle tracking analysis (NTA), atomic force microscopy (AFM), dot-blotting and flow cytometry were applied for EVs characterization. With the original technology of immunosorption we have demonstrated an increased amount of CLRN3, GAL4 and Meprin A, i.e. positive EVs in plasma of CRC patients comparing to healthy donors. Based on the quantitative analysis of such EVs, new methods of diagnostics and monitoring of CRC therapy can be developed.

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