Clinical and genetic risk factors for Fulvestrant treatment in post-menopause ER-positive advanced breast cancer patients

• Type of Material: Article
• Authors: Jingyu Liu, Central South University; Jing Li, Central South University; Hui Wang, Emory University; Qiongzhi He, Geneplus Beijing Institute; Xuefeng Xia, Geneplus Beijing Institute; Zhe-Yu Hu, Central South University; Quchang Ouyang, Central South University
• Language: English
• Date: 2019-01-15
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12967-018-1734-x
• Title of Journal or Parent Work: Journal of Translational Medicine
• ISSN: 1479-5876
• Volume: 17
• Issue: 1
• Start Page: 27
• End Page: 27
• Grant/Funding Information: This study was supported by Natural Science Foundation of Hunan Province (2018SK2124) and Hunan Provincial Health and Sanitation Committee Foundation (B2019085).
• Keywords: Post-menopause HR-positive advanced breast cancer; 500 MG; JAPANESE WOMEN; First-line; PHASE-II; Science & Technology; ENDOCRINE THERAPY; Research & Experimental Medicine; DOUBLE-BLIND; ctDNA ERBB2 and ESR1 mutation; Medicine, Research & Experimental; SURVIVAL; Life Sciences & Biomedicine; Fulvestrant; METASTASIS; Poor progress-free survival (PFS); ANASTROZOLE; METAANALYSIS; MULTICENTER
• Research Categories: Health Sciences, Oncology

Abstract

Background: Among breast cancer (BC) patients, near 40% are post-menopause, and 70%-80% are hormone receptor (HR)-positive. About 30%-40% BC patients who are diagnosed as invasive carcinoma HR-positive BC would eventually develop metastatic breast cancers. In 2016, FALCON trial proves Fulvestrant as an effective first-line endocrine therapy for post-menopause HR-positive advanced BC (ABC) patients. But even after FALCON published, Fulvestrant is rarely used as first-line in real world ABC patients in China. Method: In this study, 136 Fulvestrant users were enrolled from 2015. To investigate the clinical and genetic risk factors for Fulvestrant treatment response in real world data, biostatistic and bioinformatic analysis tools were adopted. Result: KM curves showed that Fulvestrant first-line users had a median progression-free survival (mPFS) of 15.67 months, which was longer than the second-line users and third (or higher)-line users (mPFS = 7.47 and 5.43 months, respectively). 16 s (or higher)-line users were voluntarily received circulating tumor DNA (ctDNA) testing after progression. ctDNA testing results showed that compared to patients with PFS longer than 6 months, Fulvestrant users with PFS less than 6 months had a significantly higher mutation rate of ESR1 or ERBB2 gene (0/6 vs 6/10, Fisher's Exact p-value = 0.03). Multivariate COX regression analysis showed that clinical features, including lymph node metastasis and HER-2 positive, were significant risk factors for poor PFS [hazard ratio (HR) = 2.396 and 2.863, respectively]; high portion of estrogen receptor-positive cells was significant protective factor (HR = 0.663). Propensity-score matching (PMS) analysis suggested that visceral metastasis, prior palliative chemotherapy, and old age at Fulvestrant usage were not significant influential factor for PFS. Conclusion: First-line Fulvestrant usage could guarantee a better prognosis than higher-line usage. ESR1 or ERBB2 mutation was found to be related to poor PFS in higher-line Fulvestrant users.