Phase III randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in Japanese postmenopausal women with hormone-responsive breast cancer: N-SAS BC03 study

Abstract

Clinical trials conducted in Western countries have shown that aromatase inhibitors are associated with better disease-free survival (DFS) than tamoxifen in postmenopausal early breast cancer. Because pharmacogenetic differences in drug-metabolizing genes may cause ethnic differences, assessment of the efficacy and tolerability of aromatase inhibitors in non-white women is warranted. This open-label, randomized clinical trial included 706 postmenopausal Japanese women with hormone-receptor-positive breast cancer, who had received tamoxifen for 1 to 4 years as adjuvant therapy. This study was closed early after entry of approximately 28% of the initially planned patients. They were randomly assigned to either switch to anastrozole or to continue tamoxifen for total treatment duration of 5 years. Primary endpoints were DFS and adverse events. At a median follow-up of 42 months, the unadjusted hazard ratio was 0.69 (95% confidence interval, 0.42-1.14; P = 0.14) for DFS and 0.54 (95% CI, 0.29-1.02; P = 0.06) for relapse-free survival (RFS), both in favor of anastrozole. The incidence of thromboembolic events in the tamoxifen group and bone fractures in the anastrozole group was not excessively high. Switching from tamoxifen to anastrozole was likely to decrease disease recurrence in postmenopausal Japanese breast cancer patients. Ethnic differences in major adverse events may be attributable to a low baseline risk of these events in Japanese.

Health-related quality of life and psychological distress of breast cancer patients after surgery during a phase III randomized trial comparing continuation of tamoxifen with switching to anastrozole after adjuvant tamoxifen for 1–4 years: N-SAS BC 03

“…Such a detrimental impact might have been caused by the musculoskeletal symptoms which are known to be induced by AIs at a very high incidence [20]. Actually, the adverse event data regarding arthralgia in this trial were more common in the anastrozole group than in the tamoxifen group [14]. Although there were no items in the questionnaires used that specifically proved the joint pain, the scores of the PWB subscale of FACT were statistically significantly worse in the anastrozole group and might have affected the overall HRQOL to a certain degree.…”

“…Secondary endpoints were relapse-free survival, overall survival, and HRQOL. The results of the primary endpoints and secondary endpoints other than HRQOL were already reported [14].…”

“…Eligibility criteria were described previously [14]. In brief, postoperative postmenopausal women of 75 years old or younger with estrogen and/or progesterone receptor-positive breast cancer of stages I, IIA, IIB, IIIA, or IIIB according to the UICC-TNM classification entered the trial.…”

Effects of Exemestane, Anastrozole and Tamoxifen on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Early Breast Cancer Patients: Results of N-SAS BC 04, the TEAM Japan Substudy

“…These drugs are now widely used for treatment of postmenopausal hormone-sensitive advanced and early breast cancer [1]. In particular, postoperative adjuvant endocrine therapy with the aromatase inhibitors is a promising treatment of early breast cancer because of greater recurrence prevention, as compared with tamoxifen that used to be a standard therapy drug [2,3,4,5,6], and less frequent serious adverse events, e.g. thromboembolism and venous thrombosis [2,7,8,9].…”

“…Considering the main purpose of postoperative hormone therapy in early breast cancer patients is recurrence prevention, maintenance and management of bone health in postmenopausal breast cancer patients on long-term treatment with the aromatase inhibitors is an important clinical challenge. Although the aromatase inhibitors equally prevent breast cancer recurrence in patients in Japan, the US and Europe [6], an appropriate treatment strategy needs to be established based on data of Japanese patients because the drugs may affect bones differently depending on ethnicities [11]. …”