After completing this course, the reader will be able to:1. Discuss the value of retreatment with anthracyclines for HER-2-negative metastatic breast cancer patients who received anthracyclines as adjuvant treatment.2. Discuss the role of liposomal anthracyclines, taxanes, and combinations without anthracyclines and taxanes, or innovative treatments, including target-based agents.3. Comment on the weakness and quality of available evidence.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT

The epidermal growth factor receptor (EGFR) signaling plays a key role in tumorigenesis and it has been considered an attractive target for novel antitumoral agents. Small-molecule tyrosine kinase inhibitors such as gefitinib and erlotinib have been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) patients. However, the positive results obtained in early clinical trials with gefitinib were not confirmed in large phase 3 trials, testing the efficacy of this drug in combination with chemotherapy or as single agent. An advantage in overall survival has been observed with erlotinib as single agent in NSCLC, but not in combination with chemotherapy. Conversely, an additive effect has been observed with the combination of the monoclonal antibody cetuximab and irinotecan in heavily pretreated patients with irinotecan-refractory colorectal cancer. The combination of cetuximab and radiotherapy or chemotherapy has also shown efficacy in patients with squamous cancer cell of head and neck. However, the major limit in the development of these agents is the lack of validated predictive markers of response that might allow appropriate selection of patients. In this review, we will discuss the major issues in clinical development of such agents, focusing on the challenges in designing and conducting clinical trials with EGFR inhibitors.

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578 Background: Few data have been reported on endocrine effects of combining LHRH-analogues with aromatase inhibitors (AI) in premenopausal patients. However, promising data in postmenopausal patients make this information interesting in view of extending adjuvant AI to premenopausal patients. We are conducting a phase 3 trial (Hormonal adjuvant treatment bone effects (HOBOE)) comparing tamoxifen (Tam), letrozole (L) and L + zoledronate (Z) for the effect on bone mineral density at 1 year. Postmenopausal and premenopausal patients are eligible, the latter also receiving monthly triptorelin (Tr). Methods: This analysis is limited to 76 premenopausal patients with early endocrine-responsive breast cancer, 28 treated with Tam+Tr and 48 with L+Tr±Z, assuming that Z has no endocrine effects. Serum 17-β-estradiol, FSH, LH, Δ4-androstenedione, testosterone, dehydroepiandrosterone-solphate, progesterone, ACTH and cortisol are measured at baseline and after 6 months of treatment. We compared, for each hormone, 6-month values between treatment groups by applying Exact Wilcoxon-Mann-Whitney test. Results: Baseline values for all the hormones were comparable between treatment groups. At 6 months, statistically significant differences were found for estradiol, FSH, LH and cortisol (see table , with median and range values by treatment group). No differences were found in plasma levels of testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups. Conclusions: These data support that letrozole compared to tamoxifen, in combination with triptorelin, induces a more intense estrogen suppression also in premenopausal patients. Such evidence makes reasonable the hypothesis that the higher efficacy of letrozole versus tamoxifen shown in postmenopausal patients could be confirmed also in premenopausal patients. [Table: see text] No significant financial relationships to disclose.

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