Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 501
© 2008 American Society of Clinical Oncology

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Abstract

ER alpha genotypes and breast cancer recurrence

University of Texas, San Antonio, TX; University of Texas Health and Science Center at San Antonio, San Antonio, TX; South Texas Oncology and Hematology, San Antonio, TX; South Texas Accelerated Research Therapeutics, San Antonio, TX

501

Background: Pharmacogenomic studies have documented the importance of CYP2D6 in the metabolism of tamoxifen (TAM) and the resulting clinical outcomes. However, there is no data relating polymorphisms within the estrogen receptor to disease recurrence in patients receiving adjuvant TAM. Methods: Blood samples and clinical data were collected at baseline. Assessment of clinical data was conducted yearly to evaluate disease recurrence. A Taqman Allelic Discrimination assay was utilized for genotyping the ER alpha Pvu II polymorphism. Fisher's exact tests were used to test relationships of genotypes and disease recurrence. Cox regression analysis was used to assess time to disease recurrence and was adjusted for lymph node status, histologic grade, and tumor size. Results: Within our cohort of 301 women receiving adjuvant TAM therapy, 291 women were eligible for analysis. With a median follow-up time of 5.2 years, 5% have developed recurrent disease. Patients with the ER alpha Pvu II PP genotype had a higher risk of disease recurrence than patients with the Pp or pp genotype (OR=3.1; 95% CI 1.1 - 8.9; p=0.04). ER alpha approached statistical significance as a predictor of time to disease recurrence (HR 3.2; 95% CI 0.92 - 11.2; p=0.07). In the subpopulation of patients that were converted to an aromatase inhibitor, the PP genotype was associated with a significantly higher risk of disease recurrence, with a stronger association than in the overall cohort (OR=5.6; 95% CI 1.3 - 24.5; p=0.03). PP genotype and conversion to an aromatase inhibitor was a significant predictor of time to disease recurrence in this subpopulation (HR 12.0; 95% CI 1.7 - 83.5; p=0.01). Conclusions: Our data suggests that ER alpha PP genotype is associated with a higher risk of disease recurrence compared with Pp and pp genotypes and in a subpopulation of patients converted to an aromatase inhibitor, a shorter time to recurrence. Further investigation with a larger sample size is needed to confirm the impact of ER alpha polymorphisms on survival.

No significant financial relationships to disclose.

Abstract presentation from the 2008 ASCO Annual Meeting