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The CYP19 TTTA Repeat Polymorphism Is Related to the Prognosis of Premenopausal Stage I–II and Operable Stage III Breast Cancers

^aDepartment of Surgery, ^bDepartment of Oncology, and ^cDepartment of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; ^dCancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan; ^eDepartment of Oncology, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan; ^fGraduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; ^gInstitute of Biomedical Sciences and Life Science Library, Academia Sinica, Taipei, Taiwan

Key Words. CYP19 genetic polymorphism • Breast cancer • Prognostic factor • Survival • Adjuvant chemotherapy

Correspondence: Correspondence: Chiun-Sheng Huang, M.D., Ph.D., M.P.H., Department of Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan. Telephone: 886-2-87339036; Fax: 886-2-23635227; e-mail: huangcs{at}ntu.edu.tw

Received December 17, 2008; accepted for publication June 4, 2008.

ABSTRACT

Purpose. Given the critical role of the CYP19 gene, encoding aromatase, in estrogen synthesis and the association of the estrogen level with its TTTA repeat polymorphism, the potential influence of this polymorphism on breast cancer survival, and hence management, deserves further study.

Methods. Genotyping for the CYP19 TTTA repeat polymorphism was performed on 482 stage I–II and operable stage III Taiwanese breast cancer patients. Patients with more than seven TTTA repeats in either allele of CYP19 were defined as having the long allele. We correlated clinical variables and CYP19 genotypic polymorphism with outcome.

Results. In hormone receptor (HR)-positive breast cancers, premenopausal patients with the long allele of the CYP19 polymorphism had a significantly higher overall survival (OS) rate (8-year, 89% versus 68%; p = .003) than those without it. This difference was further demonstrated by a multivariate analysis (OS hazard ratio, 1.53; p = .041). In postmenopausal women or patients with HR-negative breast cancer, there was no significant difference in OS between patients with or without the long allele. In premenopausal women with HR-positive cancers, adequate intensity adjuvant chemotherapy did not achieve a greater OS rate than suboptimal chemotherapy in patients with the long allele, but it resulted in a significantly higher OS rate (p = .011) than suboptimal chemotherapy in women without the long allele.

Conclusion. The CYP19 TTTA repeat polymorphism is associated with survival in premenopausal women, but not in postmenopausal women, with HR-positive breast cancers. Premenopausal women with the long allele have a greater survival rate and may not gain benefit from adjuvant chemotherapy.