Status of incremental costs of first-line treatment recommended in Japanese clinical guidelines for metastatic breast cancer patients.

BACKGROUND: The increasing incidence and prevalence of breast cancer alongside diagnostic and treatment technology advances have produced a debate about the financial burden cancer places on the healthcare system and concerns about access. METHODS: This study was conducted at 51 hospitals belonging to the Breast Cancer Study Group of the Japan Clinical Oncology Group using a web-based survey. The survey period conducted from July 2021 to June 2022. The study population included patients with metastatic breast cancer who received the related treatment as their first-line therapy. The proportion of patients who selected that regimen as their first-line treatment was tabulated. The total cost increase for each current standard therapy in comparison to conventional treatments was calculated. RESULTS: A total of 702 patients (pts) were surveyed. Of those enrolled, 342 (48.7%) received high-cost treatment [estimated monthly drug costs exceeding ~500 000 Japanese Yen (JPY)]. Of these, 16 pts (4.7%) were receiving very high-cost treatment, amounting to more than 1 000 000 JPY per month. Fifty three (15.5%) of the patients who received high-cost treatment were 75 years of age or older. Of these, 1 pt (0.3%) were receiving very high-cost treatment. Analyses of incremental costs by current drugs showed that abemaciclib was costly with total additional cost of 6 365 670 JPY per patient. The total additional cost of the regimen per patient that included palbociclib was the second highest at 4011248 JPY, followed by atezolizumab at 3209033 JPY. CONCLUSIONS: The findings indicate that evaluating the financial implications of high-cost treatments requires considering not only drug prices but also analysis of total cost increase.

Long-term response to MEK inhibitor monotherapy in a patient with papillary thyroid carcinoma harboring BRAF V600E mutation.

Solid tumors harboring mutations in the Braf gene (BRAF) are currently treated by combination Braf/MEK inhibitor therapy, and there is an extensive literature on patient response rates. Alternatively, few studies have documented the clinical response of BRAF mutation-positive solid tumors to MEK inhibitor monotherapy. We report the case of a 57-year-old female diagnosed with papillary thyroid carcinoma and progressive lung metastases initially treated by total thyroidectomy and subsequent thyroid-stimulating hormone suppression therapy. Next-generation sequencing revealed that the tumor harbored a BRAF V600E mutation, and the patient was enrolled in a clinical study of the oral MEK1/2 inhibitor binimetinib. Shortly after starting treatment, the patient experienced pneumothorax due to rapid regression of lung metastases, and computed tomography after 6 months of binimetinib treatment revealed a partial sustained response. One year later, the dose was reduced because of an acneiform rash. After 5 years of binimetinib treatment, lung metastases had regrown, and treatment was switched to the oral multikinase inhibitor lenvatinib. This case demonstrates the potential of MEK inhibitor monotherapy as an alternative treatment for BRAF mutation-positive papillary thyroid carcinoma.

Flavonoids from the leaves and stems of Sedum japonicum var. senanense and their antioxidant activity.

Twenty flavonoids (1-20) were isolated from the leaves and stems of Sedum japonicum var. senanense endemic to Japan. Among them, nine compounds were reported in nature for the first time, and identified as herbacetin 3-O-neohesperidoside-8-O-(2‴-acetylxyloside) (2), gossypetin 8-O-(2″-acetylxyloside) (4), gossypetin 8-O-(3″-acetylxyloside) (5), gossypetin 3-O-glucoside-8-O-(3‴-acetylxyloside) (9), gossypetin 3-O-glucoside-8-O-(2‴,3‴-diacetylxyloside) (10), gossypetin 3-O-neohesperidoside-8-O-xyloside (11), gossypetin 3-O-neohesperidoside-8-O-(2⁗-acetylxyloside) (12), gossypetin 3-O-neohesperidoside-8-O-(3⁗-acetylxyloside) (13) and gossypetin 3-O-glucoside-8-O-xylofuranoside (14) by UV spectral survey, HR-MS, LC-MS, acid hydrolysis, NMR including 1H and 13C NMR, COSY, NOESY, HSQC and HMBC. Moreover, nine major flavonoids were surveyed for antioxidant activity by H-ORAC method. As the results, gossypetin 3-O-glucoside-8-O-(2‴-acetylxyoside) (8) showed the highest antioxidant activity. Conversely, gossypetin 3-O-neohesperidoside-8-O-xyloside (11) and gossypetin 3-O-neohesperidoside-8-O-(2⁗-acetylxyloside) (12) which attach neohesperidose showed the lowest values.

Involvement of the vagus nerve and hepatic gene expression in serum adiponectin concentrations in mice

Several humoral factors, such as adiponectin and urate, have been suggested to affect metabolic syndromes. Previously, we reported a reduction in blood adiponectin concentrations after a high-fructose diet partially via the vagus nerve in rats. Although a lithogenic diet (LD), i.e., supplementation of a normal control diet (CT) with 0.6% cholesterol and 0.2% sodium cholate, reduced blood adiponectin concentrations, the involvement of the vagus nerve in this mechanism remains unclear. To estimate the involvement of the vagus nerve in the regulation of blood adiponectin concentrations using an LD, male imprinting control region mice that had been vagotomized (HVx) or only laparotomized (Sham) were administered a CT or an LD for 10 weeks. Serum adiponectin concentrations in the Sham-LD, HVx-CT, and HVx-LD groups were reduced by half compared with the Sham-CT group. The hepatic mRNA levels of fibroblast growth factor 21 (Fgf21), which reportedly stimulates adiponectin secretion from white adipose tissue, were lower in the LD groups compared with the CT groups. HepG2 hepatoma cells showed that various bile acids reduced the mRNA expression of FGF21. Moreover, the LD increased serum urate concentrations and reduced hepatic expressions of the acyl-CoA oxidase 1 (Acox1) mRNA and glucokinase, suggesting insufficient regeneration of ATP from AMP. In conclusion, serum adiponectin concentration may be regulated via the vagus nerve in normal mice, whereas a reduction of hepatic Fgf21 mRNA by bile acids may also lower serum adiponectin levels. Moreover, the LD may promote hepatic AMP accumulation and subsequently increase the serum urate concentration in mice. (AU)

Involvement of the vagus nerve and hepatic gene expression in serum adiponectin concentrations in mice

Several humoral factors, such as adiponectin and urate, have been suggested to affect metabolic syndromes. Previously, we reported a reduction in blood adiponectin concentrations after a high-fructose diet partially via the vagus nerve in rats. Although a lithogenic diet (LD), i.e., supplementation of a normal control diet (CT) with 0.6% cholesterol and 0.2% sodium cholate, reduced blood adiponectin concentrations, the involvement of the vagus nerve in this mechanism remains unclear. To estimate the involvement of the vagus nerve in the regulation of blood adiponectin concentrations using an LD, male imprinting control region mice that had been vagotomized (HVx) or only laparotomized (Sham) were administered a CT or an LD for 10 weeks. Serum adiponectin concentrations in the Sham-LD, HVx-CT, and HVx-LD groups were reduced by half compared with the Sham-CT group. The hepatic mRNA levels of fibroblast growth factor 21 (Fgf21), which reportedly stimulates adiponectin secretion from white adipose tissue, were lower in the LD groups compared with the CT groups. HepG2 hepatoma cells showed that various bile acids reduced the mRNA expression of FGF21. Moreover, the LD increased serum urate concentrations and reduced hepatic expressions of the acyl-CoA oxidase 1 (Acox1) mRNA and glucokinase, suggesting insufficient regeneration of ATP from AMP. In conclusion, serum adiponectin concentration may be regulated via the vagus nerve in normal mice, whereas a reduction of hepatic Fgf21 mRNA by bile acids may also lower serum adiponectin levels. Moreover, the LD may promote hepatic AMP accumulation and subsequently increase the serum urate concentration in mice. (AU)

Involvement of the vagus nerve and hepatic gene expression in serum adiponectin concentrations in mice.

Several humoral factors, such as adiponectin and urate, have been suggested to affect metabolic syndromes. Previously, we reported a reduction in blood adiponectin concentrations after a high-fructose diet partially via the vagus nerve in rats. Although a lithogenic diet (LD), i.e., supplementation of a normal control diet (CT) with 0.6% cholesterol and 0.2% sodium cholate, reduced blood adiponectin concentrations, the involvement of the vagus nerve in this mechanism remains unclear. To estimate the involvement of the vagus nerve in the regulation of blood adiponectin concentrations using an LD, male imprinting control region mice that had been vagotomized (HVx) or only laparotomized (Sham) were administered a CT or an LD for 10 weeks. Serum adiponectin concentrations in the Sham-LD, HVx-CT, and HVx-LD groups were reduced by half compared with the Sham-CT group. The hepatic mRNA levels of fibroblast growth factor 21 (Fgf21), which reportedly stimulates adiponectin secretion from white adipose tissue, were lower in the LD groups compared with the CT groups. HepG2 hepatoma cells showed that various bile acids reduced the mRNA expression of FGF21. Moreover, the LD increased serum urate concentrations and reduced hepatic expressions of the acyl-CoA oxidase 1 (Acox1) mRNA and glucokinase, suggesting insufficient regeneration of ATP from AMP. In conclusion, serum adiponectin concentration may be regulated via the vagus nerve in normal mice, whereas a reduction of hepatic Fgf21 mRNA by bile acids may also lower serum adiponectin levels. Moreover, the LD may promote hepatic AMP accumulation and subsequently increase the serum urate concentration in mice.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides.

(1) Background: Protein stimulates the secretion of glucagon (GCG), which can affect glucose metabolism. This study aimed to analyze the metabolic effect of a high-protein diet (HPD) in the presence or absence of proglucagon-derived peptides, including GCG and GLP-1. (2) Methods: The response to HPD feeding for 7 days was analyzed in mice deficient in proglucagon-derived peptides (GCGKO). (3) Results: In both control and GCGKO mice, food intake and body weight decreased with HPD and intestinal expression of Pepck increased. HPD also decreased plasma FGF21 levels, regardless of the presence of proglucagon-derived peptides. In control mice, HPD increased the hepatic expression of enzymes involved in amino acid metabolism without the elevation of plasma amino acid levels, except branched-chain amino acids. On the other hand, HPD-induced changes in the hepatic gene expression were attenuated in GCGKO mice, resulting in marked hyperaminoacidemia with lower blood glucose levels; the plasma concentration of glutamine exceeded that of glucose in HPD-fed GCGKO mice. (4) Conclusions: Increased plasma amino acid levels are a common feature in animal models with blocked GCG activity, and our results underscore that GCG plays essential roles in the homeostasis of amino acid metabolism in response to altered protein intake.

Correction to: Vitiligo and tumor response in a patient with amelanotic melanoma undergoing nivolumab treatment.

[This corrects the article DOI: 10.1007/s13691-021-00515-w.].

Vitiligo and tumor response in a patient with amelanotic melanoma undergoing nivolumab treatment.

Vitiligo, an acquired depigmenting disorder of the skin that reacts against normal melanocytes, sometimes occurs as an immune-related adverse event in the treatment of melanoma with immune checkpoint inhibitors. It has been known that the occurrence of vitiligo is associated with a favorable therapeutic response in patients with melanoma, but it is not yet clear whether the association also applies to amelanotic melanoma, a minor subtype of melanoma with little or no melanin pigmentation. We report a patient with amelanotic melanoma of the esophagus who responded well to nivolumab treatment. Shortly after the tumor response, vitiligo was found on the patient's forearms. This case suggests that the occurrence of vitiligo is associated with a favorable response to nivolumab treatment for amelanotic melanoma.

Drug-induced thrombocytopenia associated with trastuzumab in a patient with HER2-positive recurrent gastric cancer.

Here, we report a 57-year-old female patient with HER2-positive recurrent gastric cancer who experienced drug-induced thrombocytopenia associated with trastuzumab, a humanized anti-HER2 monoclonal antibody. Shortly after the initiation of S-1, oxaliplatin, and trastuzumab chemotherapy, the patient experienced severe thrombocytopenia and did not respond to platelet transfusions. Based on the findings of increased numbers of polynuclear megakaryocytes in the bone marrow and an elevated level of platelet-associated IgG (PA-IgG), the patient was diagnosed with drug-induced thrombocytopenia (DITP). The platelet count recovered rapidly with oral prednisolone (1 mg/kg). Since we initially suspected oxaliplatin as the causal agent, S-1 was restarted as a monotherapy, followed by trastuzumab after a 3-week interval, without oxaliplatin. On the second day after the addition of trastuzumab, severe thrombocytopenia occurred again, which suggests that trastuzumab was responsible for the DITP. The patient no longer experienced severe thrombocytopenia during the subsequent S-1 and oxaliplatin chemotherapy, which supports this hypothesis.

Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer.

The platelet isoform of phosphofructokinase (PFKP) is one of the key enzymes in the glycolytic pathway. PFKP is highly expressed in several cancers, and it has been reported to be involved in the progression of cancer cells. However, its oncological role in breast cancer (BC) remains unclear. The present study aimed to evaluate the function of PFKP in BC cells and its expression level in patients with BC. Firstly, the mRNA and protein expression of PFKP was evaluated in BC and non­cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to evaluate the correlation between PFKP and 84 cancer­related genes. Then, PFKP knockdown was conducted using small interfering RNA, and cell proliferation, invasiveness and migration were analyzed. Furthermore, the association between PFKP mRNA expression and clinicopathological factors was investigated in 167 patients with BC. PFKP was highly expressed in estrogen receptor­negative and human epidermal growth factor receptor 2­negative BC cell lines. PCR array analysis demonstrated that the expression level of PFKP was significantly correlated with that of transforming growth factor­ß1 and MYC proto­oncogene. PFKP knockdown significantly decreased the proliferation and invasiveness of MCF7, SK­BR­3, and MDA­MB­231 cells. Furthermore, cell migration was inhibited in SK­BR­3 and MDA­MB­231 cells. In the clinical specimens, patients with T2/T3/T4, lymph node metastasis, or stage II/III/IV exhibited higher expression of PFKP mRNA than patients with less severe disease. In conclusion, the present findings indicated that PFKP is involved in promoting tumor­progressive oncological roles in BC cells across different subtypes and is considered a possible novel therapeutic target for BC.

Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer.

BACKGROUND: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. METHODS: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients' clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. RESULTS: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. CONCLUSION: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways.

Bile acids induced hepatic lipid accumulation in mice by inhibiting mRNA expression of patatin-like phospholipase domain containing 3 and microsomal triglyceride transfer protein.

Preliminary studies have shown that a lithogenic diet (LG), which contains cholesterol and cholic acid, induces gallstones and hepatic lipid accumulation (HLA), and reduction of blood triglyceride in mice. We hypothesized that an LG induces HLA by diminishing hepatic triglyceride excretion; however, there is no clear understanding of the mechanism of LG-induced HLA. This study aimed to investigate transcript expression related to the synthesis, expenditure, and efflux of hepatic triglyceride, in mice fed an LG for 4 weeks. Results showed lower plasma concentrations of triglyceride in the LG group than in the control group, but no symptoms of hepatic injury were observed. Hepatic mRNA expressions of patatin-like phospholipase domain containing 3 (Pnpla3), microsomal triglyceride transfer protein (Mttp), and acyl-CoA oxidase 1 (Acox1) were also reduced in the LG group. Deoxycholic acid and lithocholic acid promoted intracellular lipid accumulation, reduced triglyceride concentration in media, and suppressed expression of PNPLA3 and MTTP in HepG2 human hepatoma cells. These findings suggest that deoxycholic acid and lithocholic acid promote HLA by inhibiting the expression of PNPLA3, ACOX1, and MTTP that are involved in lipid metabolism.

Identifying the tumor-progressive gene expression profile in high-risk papillary thyroid cancer.

PURPOSE: Papillary thyroid cancer (PTC) is generally associated with a favorable prognosis. However, some patients have fatal disease, with locally infiltrating tumors or progressive distant metastases; yet few studies have investigated the characteristics of the tumor-progressive gene expression profile in advanced PTC. We conducted this study to clarify the gene expression status in advanced PTC and identify candidate molecules for prognostic biomarkers. METHODS: We analyzed 740 tumor-progressive gene expression levels from formalin-fixed paraffin-embedded blocks of samples from six patients with low-risk PTC and six patients with high-risk PTC, using the nCounter PanCancer Progression panel. Then, we investigated the association between the expression levels of focused genes and pathological factors in PTC patients in The Cancer Genome Atlas (TCGA) database. RESULTS: The expression levels of 14 genes in the high-risk PTC specimens were more than two-fold those in the low-risk PTC specimens. In the TCGA database, expression levels of four genes (CCL11, COL6A3, INHBA, and SRPX2) were significantly higher in patients with advanced PTC. Among the patients with advanced PTC, those with high SRPX2 expression levels had poor disease-free survival. Univariate and multivariate analyses revealed that high SRPX2 expression was an independent prognostic factor. CONCLUSION: Based on the findings of this study, CCL11, COL6A3, INHBA, and SRPX2 are potential biomarkers that indicate advanced PTC. SRPX2, in particular, is considered a prognostic biomarker.

Chemotherapy for biliary tract cancer: real-world experience in a single institute.

The standard chemotherapy regimen for unresectable or recurrent biliary tract cancer is gemcitabine combined with cisplatin (GC). To evaluate the effectiveness and safety of chemotherapy in patients with unresectable or recurrent biliary tract cancer in the real world, we retrospectively analyzed the clinical courses of patients who underwent chemotherapy with GC from January 2015 to November 2019. Forty-eight patients underwent the GC regimen. One patient (2.1%) achieved a complete response, seven patients (14.6%) achieved a partial response, 26 patients (54.2) achieved stable disease, 11 patients (22.9%) achieved progressive disease, and 3 patients (6.3%) were not evaluable. The overall response rate was 16.7%. The median overall survival was 14.2 months (95% CI: 13.8-14.6), and the median progression-free survival was 7.7 months (95% CI: 4.2-11.2). Thirty-nine patients (81.3%) experienced grade 3 or higher severe adverse events as follows: 54.2% experienced neutropenia, 20.8% experienced anemia, 12.5% experienced thrombocytopenia and 20.8% experienced biliary tract infection. As a second-line chemotherapy, S-1 was used in seventeen patients, and stable disease was achieved in three patients (17.6%). The GC regimen for biliary tract cancer is effective and safe for unresectable or recurrent biliary tract cancer in routine clinical practice.

MZB1 expression indicates poor prognosis in estrogen receptor-positive breast cancer.

Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, MZB1 mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. MZB1 mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of MZB1 mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker.

Consumption of lycopene-rich tomatoes improved glucose homeostasis in rats via an increase in leptin levels.

The lycopene content of tomatoes is important because of its effects on vital physiological functions such as improvement of glucose tolerance and non-alcoholic fatty liver disease. To investigate the influence of the lycopene content of tomatoes on glucose tolerance and hepatic lipid content, homogenates of lycopene-rich (LR) or lycopene-free negative control (NC) tomato varieties were administrated to normal rats for 4 weeks. At the end of the experiment, an oral glucose tolerance test (OGTT) was performed. Rats were fed once and then dissected. According to the OGTT results, plasma glucose levels in the LR group were 10% and 9% lower at 15 min and 30 min, respectively, than those in the NC group, whereas plasma insulin levels did not differ between the groups at either time point. Upon dissection, plasma leptin levels in the LR group were higher than those in the NC group, while plasma adiponectin levels did not differ between groups. With the exception of retinol palmitate, no carotenoids were detected in the liver by HPLC analysis. Hepatic retinol palmitate levels and hepatic triacyl glyceride levels did not differ between the groups. We concluded that in normal rats, a lycopene-rich tomato variety improved glucose tolerance via an increase in plasma leptin levels that enhanced insulin sensitivity but did not affect carotenoid accumulation or lipid metabolism.

Effect of 12-Week Daily Intake of the High-Lycopene Tomato (Solanum Lycopersicum), A Variety Named "PR-7", on Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels ≥120 to <160 mg/dL. The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50 g of semidried PR-7 (lycopene, 22.0-27.8 mg/day) each day for 12 weeks, while subjects in the placebo group ingested placebo semidried tomato. Medical interviews were conducted, vital signs were monitored, body composition was determined, and blood and saliva samples were taken at weeks 0 (baseline), 4, 8, and 12. The primary outcome assessed was LDL-C. The intake of high-lycopene tomato increased lycopene levels in this group compared to levels in the placebo group (p < 0.001). In addition, high-lycopene tomato intake improved LDL-C (p = 0.027). The intake of high-lycopene tomato, PR-7, reduced LDL-C and was confirmed to be safe.

RASEF expression correlates with hormone receptor status in breast cancer.

Breast cancer (BC) is the most frequently diagnosed malignant tumor in women worldwide, and the development of new molecules associated with BC is essential for the management of this disease. RAS and EF-hand domain-containing (RASEF) encodes the GTPase enzyme that belongs to the Rab family. Although the effects of this gene have been reported in several malignant tumor types, the role of RASEF in BC has not been completely elucidated. The aim of the present study was to investigate the importance of RASEF expression in BC. RASEF mRNA expression levels were evaluated in BC and non-cancerous mammary cell lines. The association between RASEF mRNA expression levels and clinicopathological factors in 167 patients with BC were then determined. Among the 13 examined BC cell lines, ER-negative/HER2-negative cell lines expressed lower RASEF mRNA levels, when compared with the other examined cell lines (P=0.014). Of the 167 patients examined, patients with negative hormone receptor status exhibited significantly lower RASEF mRNA expression levels (P<0.001). In addition low RASEF expression in BC tissues was associated with negative estrogen receptor status (P<0.001), negative progesterone receptor status (P<0.001), and triple-negative status (P<0.001). Additionally, although the differences were not statistically significant, patients with low RASEF expression levels exhibited poorer disease-free survival (P=0.123) and overall survival (P=0.086) than other patients. The results of the present study indicate that RASEF mRNA expression levels are associated with hormone receptor status in BC.