Impact of Visceral Metastasis on Efficacy of Fulvestrant in Patients with Hormone Receptor-positive Recurrent Breast Cancer

Koi, Yumiko; Koga, Chinami; Sayuri, Akiyoshi; Masuda, Takanobu; Ijichi, Hideki; Nakamura, Yoshiaki; Ishida, M.; Ohno, Shinji; Tokunaga, Eriko

doi:10.21873/anticanres.12387

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…And the efficacy of Fulvestrant in the visceral metastasis subgroup in the study failed to show advantage over AIs 17 . Another clinical study have reached a similar conclusion that presence of visceral metastasis was a risk factor for the efficacy of fulvestrant 21 . On the contrary, a meta-analysis comparing Fulvestrant therapy with aromatase inhibitors by Graham et al showed that women with visceral metastasis derive higher benefits from Fulvestrant treatment 22 .…”

Section: Introductionmentioning

confidence: 58%

“…However, in presence chemotherapy intolerance or asymptomatic visceral metastases, endocrine therapy was still an optional treatment. Previous studies 17 , 21 have demonstrated no significant advantage over anastrozole in Fulvestrant users with visceral metastases. Similarly, in our study the PFS in patients with visceral metastases was significantly shorter despite receiving Fulvestrant as first-line endocrine therapy ( p =0.021).…”

Section: Discussionmentioning

confidence: 88%

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Efficacy and Safety of Fulvestrant 500mg in Hormone-receptor Positive Human Epidermal Receptor 2 Negative Advanced Breast Cancer: A Real-world Study in China

Lei

Song

et al. 2020

J. Cancer

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Background: Fulvestrant 500mg has proved its clinical effectiveness in previous trials as primary or second line treatment of hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2˗) post-menopausal advanced breast cancer. This real-world study aimed to investigate the efficacy and safety of Fulvestrant in HR+/HER2˗ Chinese advanced breast cancer patients. Method: HR+/HER2˗ advanced breast cancer patients who received Fulvestrant 500mg from January 2015 to December 2018 in Beijing Cancer Hospital were enrolled in this retrospective study. Progression free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and adverse events (AEs) of Fulvestrant were investigated. Result: In total 303 enrolled patients [median age was 51 years (range: 21-82)], 255 (84.2%) patients were at postmenopausal status at the start of Fulvestrant treatment and 264 patients (87.1%) had advanced breast cancer. The median PFS (95% confidence interval) was 14.1 months (10.1-18.0) for the first-line, 11.2 months (2.2-20.3) for the second-line and 6.7 months (4.8-8.5) for ≥third-line of Fulvestrant. The ORR and CBR were 3.8% and 86.8% for the first-line, 5.5% and 75.4% for the second-line, 1.1% and 61.1% for ≥third-line of Fulvestrant. The multivariate subgroup analyses showed, PFS was significantly longer for the patients with light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free interval. For patients receiving Fulvestrant after palliative chemotherapy, the median PFS was numerically greater in maintenance treatment group than those who progressed after chemotherapy. Only 5.0% of patients (15/303) experienced adverse events and majority were grade 1-2. The most common adverse event was headache and palpitation, with merely one patient had severe adverse event (pulmonary embolism). Conclusion: Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2˗ metastatic breast cancer. Light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free survival (DFS) might be the ideal condition of Fulvestrant treatment. Fulvestrant can be effective for premenopausal patients with drug-induced menopause. Patients of different luminal subtypes can benefit from Fulvestrant. For patients with visceral metastases, presence of liver metastases rather than lung metastases was poor prognostic factor. Fulvestrant may also be considered as a maintenance treatment after first-line palliative chemotherapy.

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Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 88%

Efficacy and Safety of Fulvestrant 500mg in Hormone-receptor Positive Human Epidermal Receptor 2 Negative Advanced Breast Cancer: A Real-world Study in China

Lei

Song

et al. 2020

J. Cancer

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“…Based on a multi-center retrospective analysis among ABC Fulvestrant users, patients with first-line usage, no prior palliative chemotherapy, and lower histology/nuclear grade have better prognosis; visceral metastasis have no significant effect on prognosis [12]. Some other opinions are obtained from Graham research findings; they support that patients with visceral metastasis benefit more from Fulvestrant treatment [13, 14].…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Wang

et al. 2019

J Transl Med

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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.

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Targeting metabolic adaptations in the breast cancer–liver metastatic niche using dietary approaches to improve endocrine therapy efficacy

Zuo

Mogol

Liu

et al. 2021

Preprint

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Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor agonist fulvestrant (Fulv) as standard of care. Yet, among such patients, metastasis in liver is associated with reduced overall survival compared to other metastasis sites. The factors underlying the reduced responsiveness of liver metastases to ER agonists remain unknown, impeding the development of more effective treatment approaches to improve outcomes for patients with ER+ liver metastases. We therefore evaluated site-specific changes in MBC cells and determined the mechanisms through which the liver metastatic niche specifically influences ER+ tumor metabolism and drug resistance. We characterized ER activity of MBC cells both in vitro, using a novel system of tissue-specific extracellular matrix hydrogels representing the stroma of ER+ tumor metastatic sites (liver, lung and bone), and in vivo, in liver and lung metastasis mouse models. ER+ metastatic liver tumors and MBC cells grown in liver hydrogels displayed upregulated expression of glucose metabolism enzymes in response to Fulv. Furthermore, differential ERα activity, but not expression, was detected in liver hydrogels. In vivo, increased glucose metabolism led to increased glycogen deposition in liver metastatic tumors, while a fasting-mimicking diet increased efficacy of Fulv treatment to reduce the metastatic burden. Our findings identify a novel mechanism of endocrine resistance driven by the liver tumor microenvironment. These results may guide the development of dietary strategies to circumvent drug resistance in liver metastasis, with potential applicability in other metastatic diseases.

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Impact of Visceral Metastasis on Efficacy of Fulvestrant in Patients with Hormone Receptor-positive Recurrent Breast Cancer

Abstract: Fulvestrant is more effective for patients with non-visceral metastasis of recurrent breast cancer with than for those with visceral metastasis.

Cited by 4 publications

References 19 publications

Efficacy and Safety of Fulvestrant 500mg in Hormone-receptor Positive Human Epidermal Receptor 2 Negative Advanced Breast Cancer: A Real-world Study in China

Efficacy and Safety of Fulvestrant 500mg in Hormone-receptor Positive Human Epidermal Receptor 2 Negative Advanced Breast Cancer: A Real-world Study in China

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

Targeting metabolic adaptations in the breast cancer–liver metastatic niche using dietary approaches to improve endocrine therapy efficacy

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