Comparative efficacy & safety of buparlisib plus fulvestrant, fulvestrant plus dalpiciclib, and ribociclib plus letrozole for postmenopausal, hormone receptor-positive, and HER2-negative breast cancer

Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Study on the mechanism of oridonin to reverse drug resistance of breast cancer cell MCF- 7 to fulvestrant / 中国药房

OBJECTIVE To explore the mechanism of oridon in（Ori）reversing the drug resistance of breast cancer cell MCF-7 to fulvestrant （Ful）. METHODS Ful-resistant breast cancer cell strains MCF- 7/Ful were induced and constructed in vitro . The relative cell viability of MCF- 7 cells and MCF- 7/Ful cells was detected by MTT assay ，inhibitory rate of Ori to MCF- 7/Ful cells was also detected. CompuSyn software was used to analyze the synergistic effect of Ori and Ful. MCF- 7/Ful cells were randomly divided into blank control group ，Ful group （5 μmol/L），Ori group （8 μmol/L），Ful（5 μmol/L）+Ori（8 μmol/L）group. The phosphorylation of phosphatidylinositol 3 kinase（PI3K）/protein kinase B （Akt）signaling pathway related protein in each group was detected by Western blot. MCF-7/Ful cells were used to prepare drug resistance model of transplanted tumor in nude mice，and they were randomly divided into blank control group ，Ful group （80 μmol/g），Ori group （50 μmol/g），Ful（80 μmol/g）+ Ori（50 μmol/g）group. The tumor weight and tumor inhibition rate were calculated ，to verify the reversal effect of Ori and Ful in vivo. RESULTS MTT assay showed that when Ful ≥10 μmol/L，the relative cell viability of MCF- 7/Ful cells was significantly higher than that of MCF- 7 cells（P＜0.05），and the drug resistance was significantly enhanced ；Ori had a significant inhibitory effect on MCF- 7/Ful cells ，the inhibition rate of Ori combined with Ful to MCF- 7/Ful cells was significantly increased （P＜0.05 or P＜0.01），and the effect of reversing drug resistance was significantly increased . The results of Western blot showed that compared with Ful group ，the phosphorylation levels of PI 3K and Akt protein in Ful+Ori group were significantly decreased （P＜0.05 or P＜ 0.01）. In vivo results showed that the tumor volume and mass of Ful+Ori group were significantly decreased ，and the tumor inhibition rate was （63.90±4.11）％，which was significantly higher than that of Ful group （P＜0.01）. CONCLUSIONS Ori can reverse drug resistance of breast cancer cell MCF- 7 to Ful ， and this effect may be through regulating PI 3K/Akt signaling pathway.

Research advances in the mechanisms of fulvestrant resistance / 中国肿瘤临床

Fulvestrant is a selective estrogen receptor degrader (SERD), that can specifically bind to estrogen receptor (ER), block ER transcription activity, and induce the degradation of ER protein. However, along with its widespread use in breast cancer endocrine therapy, drug resistance does gradually develop. A better understanding of mechanisms on fulvestrant resistance and the exploration on precise targeted therapy is the key to breaking through treatment bottlenecks and subsequently improving the prognosis of patients. Here, we review research advances in the potential mechanisms of fulvestrant resistance and outline promising approaches such as combination therapy to overcome the resistance.

Effects of ICI 182, 780, an ERα and ERß antagonist, and G-1, a GPER agonist, on autophagy in breast cancer cells / Efeitos do antagonista seletivo do REα e do REß ICI 182, 780 e do agonista de GPER G-1 no processo de autofagia em células de câncer de mama

ABSTRACT Objective To investigate if ICI 182,780 (fulvestrant), a selective estrogen receptor alpha/beta (ERα/ERβ) antagonist, and G-1, a selective G-protein-coupled receptor (GPER) agonist, can potentially induce autophagy in breast cancer cell lines MCF-7 and SKBr3, and how G-1 affects cell viability. Methods Cell viability in MCF-7 and SKBr3 cells was assessed by the MTT assay. To investigate the autophagy flux, MCF-7 cells were transfected with GFP-LC3, a marker of autophagosomes, and analyzed by real-time fluorescence microscopy. MCF-7 and SKBr3 cells were incubated with acridine orange for staining of acidic vesicular organelles and analyzed by flow cytometry as an indicator of autophagy. Results Regarding cell viability in MCF-7 cells, ICI 182,780 and rapamycin, after 48 hours, led to decreased cell proliferation whereas G-1 did not change viability over the same period. The data showed that neither ICI 182,780 nor G-1 led to increased GFP-LC3 puncta in MCF-7 cells over the 4-hour observation period. The cytometry assay showed that ICI 182,780 led to a higher number of acidic vesicular organelles in MCF-7 cells. G-1, in turn, did not have this effect in any of the cell lines. In contrast, ICI 182,780 and G-1 did not decrease cell viability of SKBr3 cells or induce formation of acidic vesicular organelles, which corresponds to the final step of the autophagy process in this cell line. Conclusion The effect of ICI 182,780 on increasing acidic vesicular organelles in estrogen receptor-positive breast cancer cells appears to be associated with its inhibitory effect on estrogen receptors, and GPER does notseem to be involved. Understanding these mechanisms may guide further investigations of these receptors' involvement in cellular processes of breast cancer resistance.

RESUMO Objetivo Avaliar o efeito dos compostos ICI 182,780 (fulvestranto), um antagonista seletivo dos receptores de estrógeno alfa/beta (REα/REβ), e do G-1, um agonista seletivo de receptores de estrógeno acoplados a proteínas-G (GPER), na possível indução de autofagia em linhagens de câncer de mama MCF-7 e SKBr3, bem como o efeito de G-1 na viabilidade celular. Métodos A viabilidade celular de células MCF-7 e SKBr3 foi avaliada pelo ensaio com MTT. Para investigar a indução da autofagia, células MCF-7 foram transfectadas com GFP-LC3, um marcador de autofagossomos, e analisadas por microscopia de fluorescência em tempo real. As células MCF-7 e SKBr3 foram incubadas com o indicador de compartimentos ácidos laranja de acridina e analisadas por citometria de fluxo como indicativo para autofagia. Resultados Em células MCF-7, o ICI 182,780 e rapamicina após 48 horas levaram à diminuição da viabilidade celular, enquanto o G-1 não alterou a viabilidade no mesmo período de tratamento. Nem o ICI 182,780 e nem o G-1 induziram aumento na pontuação de GFP-LC3 em células MCF-7 até 4 horas. Já os ensaios de citometria de fluxo demonstraram que ICI 182,780 levou ao aumento de compartimentos ácidos em células MCF-7. O G-1 não aumentou estes parâmetros em ambas as linhagens. Por outro lado, ICI 182,780 e G-1 não induziram à redução da viabilidade em células SKBr3 e nem à formação de compartimentos ácidos, como etapa final do processo autofágico. Conclusão O aumento de compartimentos ácidos pelo ICI 182,780 em células de câncer de mama positivas para receptores de estrógeno parece estar associado com seu efeito inibidor de receptores de estrógeno, mas sem o envolvimento de GPER. A compreensão desses mecanismos pode direcionar estudos sobre o envolvimento dos receptores nos processos celulares de resistência do câncer de mama.

Efficacy and safety comparison of everolimus and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine therapy / 实用医学杂志

Objective To compare the efficacy and safety of everolimus combined with endocrine therapy and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine thera-py. Methods Ninety-three breast cancer patients were selected from January 2014 to February 2017. The primary end points were progression-free survival and clinical benefit rate and the secondary end points was tolerability. Re-sults The progression-free survival in fulvestrant group was slightly higher than that in the everolimus group(13.4 months vs 12.2 months,P = 0.297). The clinical benefit rates were 46.15% and 31.71% in fulvestrant group and everolimus group,respectively. Patients treated with fewer than 2 lines and endocrine resistant patients benefited more from fulvestrant but without statistical difference. The main adverse events related to everolimus were stomati-tis,with a prevalence rate of about 26% and a localized pneumonia with a prevalence rate of about 10%. The main adverse reaction of fulvestrant was the injection site reaction. Conclusions The efficacy of everolimus in combina-tion with endocrine therapy is not superior to that of fulvestrant for the treatment of advanced breast cancer pro-gressed after endocrine therapy. After weighing the clinical benefits and quality of life,fulvestrant may be better for patients treated with fewer than 2 lines and endocrine resistance.

Effect of estrogen receptor antagonist on proliferation of human endometrioid carcinoma Ishikawa cells and its possible mechanism / 肿瘤

Objective: To investigate the effects of estrogen receptor (ER) antagonists tamoxifen (TAM) and fulvestrant (ICI-182780) on the proliferation of highly differentiated human endometrioid carcinoma Ishikawa cells, and to explore the possible mechanism. Methods: Ishikawa cells were cultured in vitro, and treated with ER antagonist TAM alone, ICI-182780 alone, β-estradiol alone, TAM combined with β-estradiol, ICI-182780 combined with β-estradiol, respectively; while Ishikawa cells were not treated with any drugs as the control. The cell proliferation was detected by MTT method. The changes of cell morphology were observed under a light microscope and an electron microscope, respectively. The expression levels of p57kip2 and cyclin E mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Results: Compared with the control group, the proliferation ability of Ishikawa cells in TAM group was lightly enhanced (P > 0.05), while those in the other groups were decreased (all P < 0.05). Compared with β-estradiol group, the proliferation abilities of Ishikawa cells in TAM group and β-estradiol+TAM group were increased (both P < 0.05), while those in ICI-182780 group and β-estradiol+ICI-182780 group were weakened (both P < 0.05). Compared with the control group, the cell density in β-estradiol+ICI-182780 group was reduced, while there was no obvious change in the other groups; the microvilli on the cell surface were reduced in each experimental group. The slight swelling of endoplasmic reticulum was seen in TAM group and β-estradiol group, and the moderate swelling of partial endoplasmic reticulum was seen in ICI-182780 group, while the most of endoplasmic reticulum and mitochondria had significant swelling in β-estradiol+TAM group and β-estradiol+ICI-182780 group and the autophagy increased. Compared with the control group, the expressions of p57kip2 mRNA and protein were decreased, while the expressions of cyclin E mRNA and protein were increased in the TAM group; but in other groups, the expressions of p57kip2 mRNA and protein were increased, while the expressions of cyclin E mRNA and protein were decreased. Compared with β-estradiol group, the expressions of p57kip2 mRNA and protein were increased in ICI-182780 group and β-estradiol+ICI-182780 group, while the expressions of cyclin E mRNA and protein were decreased; but in TAM group and β-estradiol+TAM group, the expressions of p57kip2 mRNA and protein were decreased, while the expressions of cyclin E mRNA and protein were increased. Conclusion: ICI-182780 can restrain the proliferation of Ishikawa cells, while TAM slightly promotes the proliferation of Ishikawa cells. The effects of ICI-182780 and TAM on endometrioid carcinoma are not completely consistent. This may be related to ICI-182780 can up-regulate the expression of the anti-oncogene p57kip2 and down-regulate the expression of the oncogene cyclin E, TAM can slightly down-regulate the expression of p57kip2 and up-regulate the expression of cyclin E. ICI-182780 may be more suitable for individual endocrine therapy of the patients with endometrioid carcinoma than TAM.

Effects of cadmium on the expression of estrogen receptor and miRNA in MCF-7 cells / 中国职业医学

OBJECTIVE: To study the effects of cadmium on the expression of estrogen receptor( ER) and miRAN-155,miRAN-200 c in human breast cancer MCF-7 cells. METHODS: MCF-7cells in logarithmic growth phase were randomly divided into fulvestrant( ICI182780,ICI) group and non-ICI group. The non-ICI group was treated with cadmium chloride(Cd Cl2) at the final concentrations of 0. 0,2. 5,5. 0 and 10. 0 μmol/L for 24 hours. The ICI group was pretreated at a concentration of 1. 0 μmol/L for 12 hours,and then treated with Cd Cl2 at the final concentrations 0. 0,2. 5,5. 0 and 10. 0μmol/L for 24 hours. The cell proliferation activity was measured by methyl thiazolyl tetrazolium assay. Flow cytometry was used to measured cell apoptosis. Western blot was applied to measure the relative expression of ERα and ERβ protein,and the relative expression of miRNA-155 and miRNA-200 c were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS: The proliferation rates of MCF-7 cells in 2. 5,5. 0 and 10. 0 μmol/L Cd Cl2 groups were significantly decreased than the 0. 0 μmol/L Cd Cl2 group( P < 0. 05). The proliferation rate in ICI group was lower than that of the non-ICI group( P < 0. 05). When Cd Cl2 concentration was 2. 5,5. 0 and 10. 0 μmol/L,the apoptosis rate of MCF-7 cells in non-ICI group increased compared with those cells without exposure to Cd Cl2( P < 0. 05). The relative expression of ERα,ERβ,miRNA-155 and miRNA-200 c increased( P < 0. 05). The proliferation of MCF-7 cells in ICI group decreased( P < 0. 05),and the relative apoptosis rate increased( P < 0. 05); and the relative expression of ERαand ERβ increased( P < 0. 05),the relative expression of miRNA-155 and miRNA-200 c decreased( P < 0. 05). When treated without Cd Cl2,the apoptosis rate of the ICI group increased compared with non-ICI group(P < 0. 05),the relative expression of ERα and ERβ decreased( P < 0. 05),and the relative expression of miRNA-155 and miRNA-200 c were increased( P < 0. 05). When Cd Cl2 concentration was 2. 5,5. 0 and 10. 0 μmol/L,the apoptosis rate and the relative expression of ERα,ERβ,miRNA-155 and miRNA-200 c decreased compared with the non-ICI group treated with same dose Cd Cl2(P < 0. 05). CONCLUSION: Cadmium can induce cell apoptosis and increase expression of miRNAs through the ER signaling pathway.

Metástasis duodenogástrica por cáncer de mama: reporte de caso / A Case Report of Duodenogastric Metastasis from Breast Cancer

Resumen Se presenta el caso de una mujer de 82 años con cáncer de mama diagnosticado en 2011 tratado con cirugía y adyuvancia hormonal con tamoxifeno. En 2015 fue hospitalizada por obstrucción intestinal alta y se descartó compromiso tumoral. Sin embargo, se realizó videotoracoscopia por presencia de derrame pleural y se documentaron lesiones pleurales correspondientes a metástasis. Se inició terapia hormonal con adecuada respuesta. Un año después, se realizó gastroduodenoscopia de control en la que se evidenció edema y eritema bulboduodenal. La biopsia corroboró compromiso metastásico por cáncer de mama.

Abstract We present the case of an 82 year old woman who was diagnosed with breast cancer in 2011 and who underwent surgery and adjuvant treatment with tamoxifen. In 2015 she was hospitalized for an upper intestinal obstruction. Involvement of a tumor was ruled out, but video-assisted thoracoscopy showed the presence of pleural effusion and pleural lesions corresponding to metastases. Hormone therapy was initiated, and the patient responded adequately. One year later, a gastroduodenoscopy showed edema and erythema of the duodenal bulb. The biopsy corroborated metastasis from breast cancer.

17β-Estradiol and fulvestrant inhibit glomerular mesangial cell fibrogenesis downstream of protein kinase C activation / 中国药科大学学报

To investigate the effect of estrogen receptor (ER) agonist 17β-estradiol and G protein-coupled estrogen receptor 1 (GPER) agonist fulvestrant on masangial cell fibrogenesis under protein kinase C (PKC),we quantified type Ⅳ collagen (COL4A1),fibronectin (FN1),connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGFβ1) gene transcription and semi-quantified phosphorylation of Akt signal upon Phorbol 12-myristate 13-acetate stimulation (which increased COL4A1,FN1,CTGF and TGFβ1 gene transcription to 2.5-0.5,1.4 ±0.2,26 ± 11 and 1.9 ±0.3 times compared with baseline,P ＜0.05) when incubated with the two drugs.It was found that 17β-estradiol and fulvestrant down-regulated COL4A1,FN1,CTGF and TGFβ1 genes transcription (P ＜0.05) and Akt signaling under PKC activation via ER and GPER.ER and GPER agonists are beneficial in protecting the mesangial cells from fibrogenic stimuli by inhibiting PKC signaling and excessive extracellular matrix production.

The growth inhibition effect of 131I-fulvestrant on the human breast cancer cells / 重庆医学

Objective To elucidate the inhibitory effect of 131I-fulvestrant on the growth of human breast cancer cells and the effect on the important organs.Methods MTT assay was used to clarify the difference in killing effects of the 131I-fulvestranton on MCF-7 cells and MDA-MB-231 cells.Breast cancer MCF-7 cell xenografts in nude mice was establishied,and two different administration methods of the 131I-fulvestrant in the MCF-7 cell to nude mice were given respectively.Organs and tumours of nude mice were observed.Results MTT assay demonstrated that 131I-fulvestrant had similar cytotoxicity against MCF-7 cells and MDA-MB-231 cells,and the former was slightly stronger.Transient contact experiments showed that 131I-fulvestrant could play a tumor suppressor effect on MCF-7 cells continually,but MDA-MB-231 cells wasn't.After the injection of 131I-fulvestrant via caudal vein,the radioactivity concentration on tumor site accounted for (4.33 ± 0.28)％ of the total injection,and the volume of the tumor reduced before gradually increasing again.Radioactivity in the blood accounted for (20.76 ± 2.54)％ of the total injection.Qrgans like liver and kidney also showed radioaction distribution.Its distribution was accorded with the distribution of estrogen receptor.Local injection of 131I-fulvestrant got powerful killing effect on the tumor,and the distribution of the radioaction was mainly confined within the tumor.Conclusion 131I-fulvestrant has a good inhibitory effect on MCF-7 breast cancer cells,which is a superposition of radiotherapy and endocrine therapy,and it is controllable on the general condition and important organs of nude mice.

Experiencia institucional con Palbociclib. Estudio Prospectivo / Institutional experience with Palbociclib. Prospective Study

La ANMAT aprobó en diciembre de 2015 el uso de palbociclib en combinación con letrozol para el tratamiento de primera línea del cáncer de mama metastásico con receptores hormonales positivos y HER2 negativo, y en agosto de 2016 la combinación de palbociclib con fulvestrant para pacientes progresadas a terapia endocrina previa. El propósito del presente estudio fue realizar una evaluación prospectiva de la seguridad y eficacia del tratamiento con palbociclib en el Instituto de Oncología Ángel Roffo. Se evaluaron en forma prospectiva 71 pacientes con cáncer de mama metastásico que calificaron para tratamiento con palbociclib desde marzo de 2016 hasta junio de 2017 inclusive. Las participantes fueron tratadas con palbociclib/letrozol (n = 49) o palbociclib/fulvestrant (n = 22). La mediana de tratamiento con palbociclib/ letrozol fue de 5 meses; 3 pacientes presentaron progresión de la enfermedad, y 36 se encuentran en respuesta parcial. La mediana de tratamiento con palbociclib/fulvestrant fue de 2.6 meses; 3 experimentaron progresión de la enfermedad, mientras que el resto de las participantes de este grupo se encuentran con respuesta parcial. En total, 26 tratadas con palbociclib presentaron toxicidades hematológicas, destacándose la neutropenia de grados I a III, anemia de grados I a II, y plaquetopenia grado III. No se registraron toxicidades de grado IV. A pesar del breve período de seguimiento (16 meses), nuestras pacientes evolucionaron con escasa cantidad de progresiones (8.4%), de acuerdo con lo descrito en la literatura, y con menor toxicidad que la comunicada (36.7%) (AU)

In December 2015, ANMAT approved the use of palbociclib in combination with letrozole for the first-line treatment of hormone-receptor-positive and HER2-negative metastatic breast cancer. Subsequently, the combination of palbociclib with fulvestrant was approved in August 2016 for patients progressing from previous endocrine therapy. The purpose of the present study was to conduct a prospective evaluation of safety and efficacy of palbociclib treatment at Instituto de Oncología Ángel H. Roffo. Seventy one patients with metastatic breast cancer who qualified for treatment with palbociclib from March 2016 to June 2017, were evaluated prospectively. Participants were treated with palbociclib/letrozole (n = 49) or palbociclib/ fulvestrant (n = 22). Median of treatment with palbociclib/letrozole was 5 months; 3 patients showed progression of the disease, and 36 are in partial response. Median of treatment with palbociclib/fulvestrant was 2.6 months; 3 patients experienced disease progression, while the rest of the participants in this group were in partial response. In total, 26 treated with palbociclib presented haematological toxicities, including neutropenia grades I to III, anaemia in grades I to II, and thrombocytopenia grade III. No grade IV toxicities were recorded. Despite the brief follow-up period (16 months), our patients experienced a low number of progression (8.4%), as described in the literature, and with less toxicity than reported (36.7%) (AU)

Effects of fulvestrant on the estrogen receptor expression in uterus and vagina of immature mice / 中国药科大学学报

@#To observe the estrogen-like effects of fulvestrant and its influence on estrogen receptor expression of fulvestrant, this study set control, fulvestrant(500 μg/kg, ip), 17β-estradiol(100 μg/kg, ig)and 17β-estradiol + fulvestrant(100 μg/kg+500 μg/kg)groups. 7 days after dosing, mice were anesthetized; their uterine and vagina were collected. HE method was used to determine morphological changes of the tissues; protein expression levels of estrogen receptor alpha(ERα)and estrogen receptor beta(ERβ)in uterus and vagina were detected by immunohistochemistry and Western blot. The results showed that fulvestrant could obviously influence the growth of the uterus and vagina and expression of estrogen receptor in immature mice. Meanwhile, fulvestrant could significantly inhibit the growth of the uterus and vagina and increase estrogen receptors expression in immature mice. The research showed that fulvestrant has anti-estrogen-like effects, which may be related to the down-regulation of estrogen receptor expression in the target organs.

A retrospective study of 500 mg fulvestrant in recurrent or metastatic breast cancer patients pretreat-ed with the third generation of aromatase inhibitors / 中国癌症杂志

Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.

Advances of fulvestrant in treatment of advanced breast cancer in hormone receptor-positive postmenopausal women / 中国癌症杂志

Endocrine therapy targeting estrogen pathway is one of the ifrst-line treatment choices of advanced breast cancer. Fulvestrant is a pure estrogen antagonist that blocks and downgrades estrogen receptor, which makes it effective in the treatment of progression after prior endocrine therapy. Fulvestrant 250 mg per month regime was approved for postmenopausal women with hormone-positive advanced breast cancer after progression or recurrence on antiestrogen therapy. Fulvestrant 500 mg per month regime was approved by the EMA and the US FDA in the same population based on the CONFIRM trial which proved improved efifcacy and similar tolerance compared with 250 mg regime. Recent trials were focused in the ifrst-line treatment and combination use with other therapeutics. This review discusses the advances of fulvestrant in postmenopausal women with hormone-positive advanced breast cancer.

Efficacy of Fulvestrant in Heavily Pretreated Postmenopausal Women with Advanced Breast Cancer: A Preliminary Report / 한국유방암학회지

PURPOSE: Fulvestrant, a potent estrogen receptor (ER) antagonist with a novel mechanism of action, has shown efficacy in pretreated patients with advanced breast cancer. We assessed the efficacy and tolerability of fulvestrant in Korean postmenopausal women. METHODS: Of the 25 candidates identified at Asan Medical Center, Seoul, Korea, six were deemed ineligible due to inadequate baseline and follow-up imaging. The 19 patients included in this retrospective analysis received the approved dose of fulvestrant (250 mg intramuscular injection, once per month) as second- (n=8), third- (n=7), or fourth-line (n=4) endocrine therapy. RESULTS: At a median follow-up of 7.4 months (range, 1.2-34.8 months), the 19 patients received a median of four cycles (range, 1-34 cycles) of fulvestrant. Median time to progression was 5.5 months (95% confidence interval [CI], 0.4-10.7 months), and median overall survival was 17.9 months (95% CI, 2.7-33.1 months). Among 17 evaluable patients, one (5.3%) achieved a partial response, 10 (52.6%) showed stable disease, and six (31.6%) showed progressive disease. The clinical benefit rate was 26.3%. Four patients (21.1%) reported adverse events, but all were grade 1 or 2. CONCLUSION: Fulvestrant was effective and well tolerated in patients with advanced breast cancer who had been previously treated with several lines of endocrine and chemotherapeutic agents.