High-dose tamoxifen in high-hormone-receptor-expressing advanced breast cancer patients: a phase II pilot study

Yanhong Su; Yarui Zhang; Xin Hua; Jiajia Huang; Xiwen Bi; Wen Xia; Xinyue Wang; Zhangzan Huang; Chenge Song; Yongyi Zhong; Yanxia Shi; Shusen Wang; South China Breast Cancer Group (SCBCG); Wei Fan; Zhongyu Yuan

doi:10.1177/1758835921993436

High-dose tamoxifen in high-hormone-receptor-expressing advanced breast cancer patients: a phase II pilot study

Ther Adv Med Oncol. 2021 Feb 26:13:1758835921993436. doi: 10.1177/1758835921993436. eCollection 2021.

Authors

Affiliations

¹ Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
² Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
³ Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510000, China.
⁴ Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510000, China.

Abstract

Background: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR.

Materials & methods: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of ¹⁶α-¹⁸F-¹⁷β-fluoroestradiol quantitative positron emission tomography/computed tomography (¹⁸F-FES PET/CT) for treatment efficacy.

Results: A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9-7.1] and the median OS was 15.6 months (95% CI 8.3-22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with ¹⁸F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9-11.6)] compared with lesions with a ¹⁸F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9-5.6); p = 0.022].

Conclusion: A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. ¹⁸F-FES SUVmax values may predict the local clinical benefits of high-dose TAM .

Trial registration: [ClinicalTrials.gov identifier: NCT0304565].

Keywords: PET; breast cancer; hormone receptor-positive breast cancer; hormone therapy; tamoxifen.