Abstract
22096 Background: Letrozole's effect in metastatic breast cancer (BC) patients was shown to be associated with a single nucleotide polymorphism (SNP) in the CYP19 aromatase gene. Two CYP19 polymorphisms; the 3'UTR rs10046 and IVS4(tct)± significantly correlate with serum estrogen levels in postmenopausal women. We evaluated their impact on response among BC patients treated with Letrozole. Methods: 70 BC patients treated with Letrozole with clinically evaluable disease (local stage III in 3, and metastatic in 67) were included. 65/67 metastatic patients, were treated with Tamoxifen before Letrozol (37-adjuvant, 28-first line for metastatic disease). DNA from whole blood was genotyped using DHLPC. Presence of WT or SNP was recorded. Correlation with tumor response (progressive, stable or responsive) in all patients and time to progression (TTP) from date of Letrozole start to progression were analyzed in 67/70 patients with metastatic disease. Results: Median age at diagnosis was 52 (range: 27–86). In 66, tumor was positive for estrogen receptor, in 2 it was negative and in additional 2 unknown. 28/70 (40%) carried the 3'UTR rs10046 wild type allele (WT). In the IVS4(tct)±, 3 genotypes, homozygous IVS4(tct)+, heterozygous IVS4(tct)± and homozygous IVS(tct)− were recorded with corresponding frequencies of 22/68 (32%), 30/68 (44%) and 15/68 (22%). These genotypes were not significantly associated with tumor response. However, median TTP was not reached at 30.4 months among carriers of IVS4 (tct)−/− allele compared with 14 and 12.7 months in heterozygots and homozygous (tct)+/+ respectively (p=0.02). Conclusion: homozygous delition of the (tct) at IVS4(tct)± of CYP19 is associated with longer TTP in patients with metastatic BC treated with Letrozole. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
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