SULT1A1 rs9282861 polymorphism-a potential modifier of efficacy of the systemic adjuvant therapy in breast cancer?

The rs9282861 genotypes of 412 Finnish breast cancer patients with early breast cancer were identified by using PCR-RFLP method. Seventy six patients were treated with adjuvant cyclophosphamide based chemotherapy only, 65 patients received adjuvant TAM, and four patients were treated with both adjuvant chemotherapy and TAM. Overall long-term survival (OS), breast cancer specific survival (BCSS), and relapse-free survival (RFS) by rs9282861 genotypes were evaluated by the Kaplan-Meier method and Cox regression analysis.The multivariate analysis of 145 patients receiving either adjuvant TAM or chemotherapy showed a statistically significantly improved OS in patients with the rs9282861 homozygous variant AA genotype (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.29-0.88, P = 0.015). In the separate analyses of patients receiving only chemotherapy or adjuvant TAM, there were no statistically significant differences in survival.In this prospective study, we observed a previously unreported association between the SULT1A1 rs9282861 genotype and OS of breast cancer patients treated with adjuvant chemotherapy or TAM. This novel finding suggests that the rs9282861 polymorphism modifies the long-term clinical outcome of patients receiving adjuvant TAM or chemotherapy.Tamoxifen (TAM) has been used for the treatment of oestrogen-receptor-positive breast cancer for three decades and still has its place in the treatment of both early and metastatic breast cancer. In the adjuvant setting it is the preferred endocrine therapy in premenopausal women and an acceptable option in postmenopausal women, especially in the group with low risk of relapse [1]. In early stage breast cancer, TAM reduces the 15-year risks of breast cancer recurrence and death by about a third [2]. Even though the benefit of adjuvant TAM persists for years, some patients will eventually relapse and die of breast cancer [2]. In addition to causing hot flushes TAM increases the risk of endometrial can