Abstract
507 Background: We have previously reported a prospective cohort study of patients with ER+ and/or PR+ metastatic breast cancer treated with the aromatase inhibitor letrozole (SABCS 2001), in which the efficacy of letrozole, measured with time to treatment progression (TTP), correlated with the levels of circulating HER2 ECD. We have now evaluated in tumor tissue samples whether SNPs of the CYP19 aromatase gene had a predictive value. CYP19 is located on chromosome 15q and encodes a steroid aromatase that catalyzes the conversion of C19 androgens to estrogens. Methods: PCR allelic discrimination (ABI prism 7700 sequence detector) was used to examine SNPs in DNA obtained from 67 breast cancer patients accrued from 04/1999 to 11/2000. Two regions of the aromatase CYP19 gene were examined, one localized in the 3' untranslated region (UTR) and one in the intronic region. Presence of wild-type gene (WT) or SNPs was recorded. All patients in the study had documented disease progression and had been treated previously with a SERM. Sixty-five patients are evaluable for efficacy. Results: Median age was 62 years, median number of metastatic sites was 2. Percentage of cases with SNP variation of CYP19 UTR was 46% and of CYP19 intronic region was 63%, respectively. Time to treatment progression was longer in patients with SNPs of CYP19 UTR when compared with CYP19 UTR WT (525 vs. 196 days, p=0.02). This relationship was not observed for CYP19 intronic region (459 vs 510 days, p=0.9). Conclusions: In hormone receptor-positive metastatic breast cancer patients treated with the aromatase inhibitor letrozole, the presence of single nucleotide polymorphisms on the 3'UTR of the CYP19 aromatase gene is associated with improved treatment efficacy, and may help in selecting patients for letrozole therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
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