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

Jingyu Liu,Zhe-Yu Hu,Quchang Ouyang,Qiongzhi He,Xuefeng Xia,Hui Wang,Yikai Wang,Jing Li

doi:10.1186/s12967-018-1734-x

Abstract

BackgroundAmong 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.MethodIn 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.ResultKM 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.ConclusionFirst-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.

Highlights

Among breast cancer (BC) patients, near 40% are post-menopause, and 70%–80% are hormone recep‐ tor (HR)-positive
First-line Fulvestrant usage could guarantee a better prognosis than higher-line usage
ESR1 or ERBB2 mutation was found to be related to poor progress-free survival (PFS) in higher-line Fulvestrant users

Summary

Introduction

Among breast cancer (BC) patients, near 40% are post-menopause, and 70%–80% are hormone recep‐ tor (HR)-positive. In 2016, FALCON trial proves Fulvestrant as an effective first-line endocrine therapy for post-menopause HR-positive advanced BC (ABC) patients. Near 40% are post-menopause, and 70%–80% are hormone receptor (HR)-positive. The goals of treatment for advanced breast cancer (ABC) patients include symptoms alleviation, quality of life (QOL) improvement, and survival extension [3]. To achieve this goal, endocrine therapy is an efficient treatment strategy to target estrogen receptor (ER), to block ER’s interaction with estrogen and to inhibit ER downstream pathways. Endocrine therapy is the first-line treatment regimen for ER-positive ABC patients [4], except for severe visceral conditions which need rapid control for the disease

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