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

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.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1734-x) contains supplementary material, which is available to authorized users.

Inhibition of Histone Demethylases LSD1 and UTX Regulates ERα Signaling in Breast Cancer

“…A step forward in BC therapy came about with the development of SERDs (e.g., fulvestrant), antagonists of ERα that also induce its proteasome-mediated degradation. Although fulvestrant is FDA-approved for advanced ERα -positive BC, the poor pharmaceutical properties of this steroid-based SERD have resulted in dose limitations, and, most importantly, not all patients benefit from fulvestrant treatment [26]. A shift from single to multi-target (epigenetic) therapeutic strategies [27,28] appears to be a valuable approach to improving BC management.…”

lncRNA CYTOR promotes tamoxifen resistance in�breast cancer cells via sponging miR‑125a‑5p

“…Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide (1). Overexpression of estrogen receptor α (ERα), is a feature of ERα + breast cancer, a major subtype of breast cancer (2). ER is a hormonal transcription factor that is activated by binding to estrogen, thus promoting cell cycle progression (3).…”

PIK3CA gene mutations in the helical domain correlate with high tumor mutation burden and poor prognosis in metastatic breast carcinomas with late-line therapies

“…A two-sided log-rank test was used to test the influence of PI3K/AKT pathway aberrations in terms of late-line treatment PFS in MBCs. To reduce the potential bias between subgroups, we also performed 1:1 propensity score matching (PSM) analysis as described previously [38]. Both the univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the prognostic factors for PFS.…”