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10617 Background: Whether trastuzumab should be continued after tumor progression remains unknown.We describe the activity of successive trastuzumab-containing regimens in patients with HER2-overexpressing metastatic breast cancer, as well as the response rate, time to progression and predictive factors for response. Methods: Descriptive retrospective study of trastuzumab activity in patients with HER2-overexpressing metastatic breast cancer treated at our hospital from 10/1999 to 07/2005. Results: 93 consecutive patients were evaluated obtaining an objective response rate (OR) for first-time administration of trastuzumab of 46.2%; stable disease (SD) 24.7%; clinical benefit (CB) 71%. Median time-to-progression (TTP) was 5 months (range: 1–39+). A total of 47 pts (50.5%) received a second trastuzumab-containing regimen with an OR of 29.8%; SD 21.3%; CB 51.1%; TTP 4 months (range: 1–31). A total of 21 pts (22.6%) received a third trastuzumab-containing regimen; OR 38.1%; SD 23.8%; CB 61.9%; TTP 4 months (range: 1–30+). A total of 10 pts (10.8%) received a fourth trastuzumab-containing regimen; OR 20%; SD 20%; CB 40%; TTP 4 months (range: 1–37). 5 pts (5.4%) received a fifth trastuzumab-containing regimen; OR 0%; SD 60%. Age < 45 years is a significant prognostic factor (p: 0.005, 95% CI, OR 5.6 (1.5–20.6)). A better response rate in the successive trastuzumab-containing regimens was observed, when there was a response in the first regimen: p = 0.04; 95% CI; OR 3.84 (1.07–14.65). With a follow-up of 16,5 months 45 pts (48,4%) are alive. Conclusions: Trastuzumab-containing therapies beyond disease progression in metastatic breast cancer show activity. There were more responses in younger pts. Those pts who had a previous response to trastuzumab therapy were more likely to respond to successive trastuzumab-containing regimens. Additional controlled studies are needed to test this approach. No significant financial relationships to disclose.

The 9p21 gene cluster, harboring growth suppressive genes p14 , p15 , and p16 , is one of the major aberration hotspots in head and neck cancers. We try to elucidate specific aberrations affecting this region, throughout methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 27 laryngeal squamous cell carcinomas and 20 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using and methylation-specific. All samples studied except 3 (11 %) presented losses at 9p21 segment. The most common finding was the small deletion (exon 1α) of the p16 locus (44 %). Deletion of the 9p21 gene cluster was identified in 5 cases (18 %). We only found methylation in 8 samples (30 %) for p15 -exon 1. Promoter methylation of p14 , p15 and p16 was not detected in any tumor sample. Methylation-specific polymerase chain reaction confirmed the results. Our data indicate that there may be a subgroup of patients in which epigenetic regulation of 9p21 segment might have little relevance. Nevertheless, MS-MLPA could not be suitable for the study of methylation at this region and further research is required.

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