Effects of 5-fluorouracil Co-administration on Blood Pressure in Patients Maintained on Antihypertensives: a Retrospective Case Series.

This study aimed to investigate the possible drug-drug interactions (DDIs) of 5-FU with antihypertensives metabolised by CYP3A4 and 2C9, using blood pressure (BP) as a pharmacodynamic (PD) parameter. Patients who received 5-FU in combination with antihypertensives metabolised by CYP3A4 or 2C9, specifically, a) amlodipine, nifedipine, or amlodipine + nifedipine, b) candesartan or valsartan, or c) amlodipine + candesartan, amlodipine + losartan, or nifedipine + valsartan, (Group A, n = 20) were identified. Patients who received 5-FU with WF and antihypertensives, specifically, a) amlodipine or b) amlodipine + telmisartan, amlodipine + candesartan, or amlodipine + valsartan, (Group B, n = 5) or 5-FU alone (Group C, n = 25) were also identified and analysed as a comparator and control group, respectively. Regarding the peak BP levels during chemotherapy, there was a significant increase in both SBP (P < 0.0002 and 0.0013) and DBP (P = 0.0243 and 0.0032) in Groups A and C, respectively (Tukey-Kramer test). In contrast, although SBP also increased in Group B during chemotherapy, the change was not statistically significant and there was a decrease in DBP. The significant increase in SBP can be attributed to chemotherapy-induced hypertension by 5-FU or other drugs in the chemotherapeutic regimens. However, when comparing the lowest BP levels during chemotherapy, there was a decrease in SBP and DBP in all groups from the baseline values. The median time to peak and lowest BP was at least 2 weeks and 3 weeks, respectively, for all groups, suggesting that a BP lowering effect was observed following the offset of the initial chemotherapy-induced hypertension. At least 1 month after 5-FU chemotherapy, the SBP and DBP returned to baseline values in all groups. Since Group B also showed a significant increase in PT-INR, possibly demonstrating 5-FU inhibition of CYP activity and, consequently, of WF metabolism, it is likely that 5-FU also inhibited the metabolism of the antihypertensive drugs. The findings suggest possible DDIs between 5-FU and antihypertensives metabolised by CYP3A4.

Relationship between the housing coldness/warmth evaluation by CASBEE Housing Health Checklist and psychological distress based on TMM Community-Based Cohort Study: a cross-sectional analysis.

OBJECTIVES: Previous studies have reported the relationship between housing environment and health, although due to cost and effort, it was difficult to conduct housing condition surveys on a large scale. The CASBEE Housing Health Checklist (the Checklist) made it possible to easily evaluate the housing condition from the resident's perspective. This study examined the relationship between housing coldness/warmth evaluation using the Checklist and psychological distress in a large-scale general Japanese population. STUDY DESIGN: A cross-sectional study. METHODS: We analysed data from 29,380 people aged ≥20 years who lived in Miyagi Prefecture, Japan. As an assessment of housing coldness/warmth, we used the Checklist. We classified participants' total scores on the Checklist related to coldness/warmth into quartiles. The Kessler 6 scale was used as an indicator of psychological distress. Multivariable logistic regression models were used to estimate the adjusted odds ratio (OR) and 95% confidence intervals (CIs). Adjusted OR and P-values for linear trends were calculated using the quartiles of the Checklists' score. RESULTS: Among participants in Q1 (i.e., poorer subjective house condition), the percentage of people with psychological distress was high. Compared to the highest quartile, Q1 showed poorer evaluation of housing coldness/warmth, and higher OR for psychological distress. The OR (95% CI) of psychological distress for Q3, Q2, and Q1 compared with Q4 were 1.93 (1.74-2.14), 2.82 (2.55-3.12), and 5.78 (5.25-6.35), respectively. CONCLUSIONS: Housing coldness/warmth evaluation was significantly related to psychological distress. This finding suggests that maintaining a comfortable thermal environment at home could be important for residents' mental health.

Ovarian reserve may influence the outcome of bone mineral density in patients with long-term use of dienogest.

OBJECTIVE: Long-term administration of dienogest, which is known to have effect on bone mineral density, is frequently done in patients with endometriosis and adenomyosis, but a few studies focused on the bone mineral density changes after finishing the long-term therapy. This study aimed to reveal the factors that adversely affect lumbar bone mineral density. METHOD: Fifty-seven premenopausal women who visited our hospital were diagnosed as either endometriosis or adenomyosis, and they were treated by dienogest for more than 115 weeks (26.5 months). Based on a previous report, bone mineral density changes less than 2% was categorized as the osteopenic group (n = 30), and the others were assigned to the unchanged group (n = 27). Bone mineral density was measured at the lumbar spine using dual-energy X-ray absorptiometry. A representative ovarian reserve marker, endogenous estradiol levels, and follicle-stimulating hormone levels were measured over time and were compared between the osteopenic and unchanged groups. RESULT: Duration of dienogest intake was 59.5 months (osteopenic group) versus 57.5 months (unchanged group). These patients experienced ovarian surgeries in a similar frequency, but the ovarian reserve in osteopenic group was impaired as suggested by the decline of endogenous estradiol level during intake of dienogest compared to that of unchanged group (p = 0.0146). Endogenous follicle-stimulating hormone level between osteopenic group and unchanged group did not reach statistically significant difference, although the osteopenic group showed relatively higher level. CONCLUSION: This study might suggest that decreased ovarian reserve as judged by endogenous estradiol level is a factor that negatively affect bone mineral density, and measurement of endogenous estradiol level during intake of dienogest could have a predictive meaning of future decreased bone mineral density level.

mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.

The mechanism by which the cytosolic protein Zap70 physically interacts with and phosphorylates its substrate, the transmembrane protein LAT, upon T cell receptor (TCR) stimulation remains largely obscure. In this study, we found that the pharmacological inhibition of formins, a major class of actin nucleators, suppressed LAT phosphorylation by Zap70, despite TCR stimulation-dependent phosphorylation of Zap70 remaining intact. High-resolution imaging and three-dimensional image reconstruction revealed that localization of phosphorylated Zap70 to the immune synapse (IS) and subsequent LAT phosphorylation are critically dependent on formin-mediated actin polymerization. Using knockout mice, we identify mDia1 and mDia3, which are highly expressed in T cells and which localize to the IS upon TCR activation, as the critical formins mediating this process. Our findings therefore describe previously unsuspected roles for mDia1 and mDia3 in the spatiotemporal control of Zap70-dependent LAT phosphorylation at the IS through regulation of filamentous actin, and underscore their physiological importance in TCR signaling.

Post-occlusional hyperemia for fractional flow reserve assessment and pull-back curve analysis.

Balloon occlusion is a potential method for inducing hyperemia to measure post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR). The objective of this study was to determine the clinical usefulness of post-occlusional hyperemia. FFRs measured using post-occlusional hyperemia caused by 30 (FFRoccl30) and 60 s (FFRoccl60) of balloon occlusion after PCI were compared in 60 lesions from 60 patients. The duration of hyperemia was also measured. There was a strong correlation between FFRoccl30 and FFRoccl60 (r = 0.969, p < 0.01). The duration of hyperemia was significantly longer with FFRoccl60 than with FFRoccl30 (68 ± 23 vs. 37 ± 15 s, p < 0.01). The time required for pullback curve analysis was around 45 s. However, in 7 (12%) cases, the duration of hyperemia with FFRoccl60 was < 45 s, which was not enough for pull-back curve analysis. To predict the duration of hyperemia with FFRoccl60 ≥ 45 s, the receiver operating characteristic curve analysis revealed a cut-off value of 25 s of hyperemia with FFRoccl30. FFRoccl30 is sufficient for diagnostic purposes. FFRoccl60 is suitable for pull-back curve analysis in select cases based on predictions made using the duration of hyperemia with FFRoccl30.

Angiogram based fractional flow reserve in patients with dual/triple vessel coronary artery disease.

OBJECTIVE: To assess the performance of angiography derived Fractional Flow Reserve (FFRangio) in multivessel disease (MVD) patients undergoing angiography. BACKGROUND: FFR is the reference standard for physiologic assessment of coronary stenosis and guidance of revascularization, especially in patients with MVD, yet it remains grossly underutilized. The non-wire based FFRangio performs well in non-MVD patients, but its accuracy in MVD is unknown. METHODS: A prospective clinical study was conducted at Gifu Heart Centre, Japan. Patients underwent physiologic assessment of all relevant coronary lesions using wire-based FFR (wbFFR) and FFRangio. Primary outcome was diagnostic performance (sensitivity, specificity, accuracy) for FFRangio with wbFFR as reference. Other outcomes were the correlation between wbFFR/FFRangio, time required for wbFFR/FFRangio measurements, and the effect of wbFFR/FFRangio on the reclassification of coronary disease severity. RESULTS: Fifty patients (118 lesions in total) were included. Mean age was 72 ±â€¯9 years, 72% were male, 36% had triple vessel disease and the average SYNTAX score was 13. The mean measurement of wbFFR and FFRangio were 0.83 ±â€¯0.12 and 0.81 ±â€¯0.11, respectively. Accuracy, sensitivity and specificity for FFRangio were 92.3% (95% CI 79.1-98.4%), 92.4% (95% CI 84.3-97.2%) and 92.4% (95% CI 87.4-97.3%), respectively. Pearson's r between wbFFR and FFRangio was 0.83. FFRangio measurement was faster than wbFFR (9.6 ±â€¯3.4 vs. 15.0 ±â€¯8.9 min, p < 0.001). CONCLUSIONS: In patients with MVD, FFRangio shows good correlation and excellent diagnostic performance compared to wbFFR, and measuring FFRangio is faster than wbFFR. These results highlight the potential clinical benefits of utilizing FFRangio among patients with MVD.

The induction of antigen-specific CTL by in situ Ad-REIC gene therapy.

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

Effect of interfacial structure on bioinert properties of poly(2-methoxyethyl acrylate)/poly(methyl methacrylate) blend films in water.

In this study, we found that the surface made of a mixture of poly(2-methoxyethyl acrylate) (PMEA) and poly(methyl methacrylate) (PMMA) exhibited excellent blood compatibility by inhibiting platelet adhesion. To obtain a better understanding of this bioinertness, the polymer/water interface was characterized by neutron reflectivity measurements and sum frequency generation spectroscopy, in conjunction with bubble contact angle measurements. Based on the results, we can say that the outermost region of the blend film was reorganized in water. When the orientation of PMEA segments at the water interface became random with increasing immersion time, the fractional amount of lower-coordinated water molecules increased at the interface. Such an interfacial structure caused the suppression of platelet adhesion.

Targeting Gli transcription activation by small molecule suppresses tumor growth.

Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anticancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study, we identified an interaction between Gli proteins and a transcription coactivator TBP-associated factor 9 (TAF9), and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and downregulate Gli/TAF9-dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, an important control point of multiple oncogenic pathways, may be an effective anticancer strategy.

Technical note: Use of a simplified equation for estimating glomerular filtration rate in beef cattle.

This study was performed to clarify whether a formula (Holstein equation) based on a single blood sample and the isotonic, nonionic, iodine contrast medium iodixanol in Holstein dairy cows can apply to the estimation of glomerular filtration rate (GFR) for beef cattle. To verify the application of iodixanol in beef cattle, instead of the standard tracer inulin, both agents were coadministered as a bolus intravenous injection to identical animals at doses of 10 mg of I/kg of BW and 30 mg/kg. Blood was collected 30, 60, 90, and 120 min after the injection, and the GFR was determined by the conventional multisample strategies. The GFR values from iodixanol were well consistent with those from inulin, and no effects of BW, age, or parity on GFR estimates were noted. However, the GFR in cattle weighing less than 300 kg, aged<1 yr old, largely fluctuated, presumably due to the rapid ruminal growth and dynamic changes in renal function at young adult ages. Using clinically healthy cattle and those with renal failure, the GFR values estimated from the Holstein equation were in good agreement with those by the multisample method using iodixanol (r=0.89, P=0.01). The results indicate that the simplified Holstein equation using iodixanol can be used for estimating the GFR of beef cattle in the same dose regimen as Holstein dairy cows, and provides a practical and ethical alternative.

Experimental infection of pregnant cows with noncytopathogenic bovine viral diarrhoea virus between days 26 and 50 postbreeding.

The effect of bovine viral diarrhoea virus (BVDV) infection on early pregnant cows between 10 and 24 days after virus inoculation at day 26 of pregnancy was determined. Four cows were inoculated intravenously with either BVDV (treated, n=3) or growth medium (control, n=1). The treated cows were euthanized on either day 10, 17 or 24 post-infection and the control cow was euthanized on day 24 post-infection. The level of serum 2-5A synthetase increased in all of the three treated cows. Progesterone levels decreased to below 1.0 ng/ml between 10 and 22 days after inoculation in two of the three treated cows and the embryos/foetuses of two cows died. Therefore, BVDV may be a cause of early embryonic or feotal loss in early pregnant cows and serum 2-5A synthetase may be useful as an indicator of viral infection in cows.

Influence of gastric acid on gastric emptying and gastric distension-induced pain response in rats--effects of famotidine and mosapride.

BACKGROUND: Gastroduodenal acidification has been reported to aggravate upper abdominal discomfort and pain that are symptoms suffered by functional dyspepsia (FD) patients. Delayed gastric emptying and hypersensitivity to gastric distension (GD) contribute importantly to the pathophysiology of FD. METHODS: In the present study, we determined the influence of pentagastrin-stimulated endogenous gastric acid on gastric emptying and GD-induced pain responses using rat model systems. Moreover, we evaluated the effects of famotidine and mosapride on changes in gastric emptying and the GD-induced pain response to gastric acid hypersecretion. Gastric emptying was measured by excretion of glass beads that had been intragastrically administered with a liquid nutrient, and gastric pain response was evaluated by observing whether a GD-induced increase in mean blood pressure occurred. KEY RESULTS: Pentagastrin (2 mg kg(-1), s.c.) which markedly and continuously stimulated gastric acid secretion, significantly delayed and enhanced respectively, gastric emptying and pain compared with saline-injected groups. Oral famotidine (0.1-3 mg kg(-1)) and mosapride (0.3-3 mg kg(-1)) administration in a dose-dependent manner accelerated the delay of gastric emptying. Furthermore, famotidine (0.3-3 mg kg(-1)) significantly alleviated the aggravation of the GD-induced pain response, but mosapride (10 mg kg(-1)) did not. CONCLUSIONS & INFERENCES: We established rat models to evaluate the effect of gastric acid hypersecretion on gastric emptying and the GD-induced pain response. In these models, acid hypersecretion delayed gastric emptying and aggravated the pain response. Furthermore, we showed that famotidine ameliorated both delayed gastric emptying and gastric hypersensitivity, whereas mosapride only improved delayed gastric emptying.

Efficacy of pleurodesis for malignant pleural effusions in breast cancer patients.

This study retrospectively compared long-term outcomes between two groups of breast cancer patients with malignant pleural effusion (MPE): those receiving only systemic therapy (ST) and those receiving ST following initial pleurodesis (P-ST). We identified 180 breast cancer patients from the National Cancer Center Hospital (Tokyo, Japan) database who had received ST and P-ST as an initial treatment for MPE between 1997 and 2008 for study inclusion. Pleural progression-free survival (PPFS) was defined as the time from ST in the ST group and from pleurodesis in the P-ST group to the first observation of pleural progression or death from any cause. Of the 180 patients, 78 received ST and 102 received P-ST after MPE diagnosis. Median duration of follow-up was 12.7 months (range 0.9-80.1 months). Median PPFS for the ST group and the P-ST group was 4.1 and 8.5 months, respectively. The difference in PPFS between the two groups was statistically significant (p < 0.001) and the hazard ratio after adjusting for prognostic factors in the P-ST group relative to the ST group was 0.24. Our results suggest that the efficacy of P-ST may be superior to that of ST alone with respect to local control of pleural effusions in breast cancer patients.

Anti-obesity compounds in green leaves of Eucommia ulmoides.

The anti-hypertensive effect of Eucommia leaves has been confirmed clinically, and the study of their anti-obesity properties has advanced. However, the compounds involved in their anti-obesity effect have not been fully elucidated. In this Letter, we examined the anti-obesity effect of Eucommia green leaf extract (EGLE) divided into five fractions with high porous polystyrene gel and of the compounds isolated, geniposidic acid, asperuloside and chlorogenic acid, respectively. A metabolic syndrome-like clinical model in mice was generated by feeding a 40% high-fat diet to examine the anti-obesity effects of chronic administration of test substance. After 4 weeks, body weight, white adipose tissue weight, plasma triglyceride levels and total cholesterol levels in the model mice were significantly inhibited by the 30% MeOH fraction (containing much higher levels of asperuloside than the other fractions), and these effects were similar to those of EGLE. Chronic administration of isolated asperuloside in Eucommia leaves suppressed increases in model mouse body weight, white adipose tissue weight, plasma triglyceride levels and free fatty acids levels. These results suggest that asperuloside in Eucommia leaves has important anti-obesity effects.

Compliance with Good Clinical Practice in oncology registration trials in Japan.

BACKGROUND: This study aimed to examine the quality in oncology registration trials for new drug application (NDA) or supplemental new drug application (sNDA) as extensions of the indications for use in Japan based on Good Clinical Practice (GCP) audit findings. MATERIALS AND METHODS: We collected audit reports of on-site GCP inspections for registration trials in 383 NDAs or sNDAs that were reviewed by the Pharmaceuticals and Medical Devices Agency between the fiscal years 2004 and 2009. RESULTS: Among the 40 audits for oncology drug applications, the frequencies at which one or more deficiencies ascribed to institution, investigator, sponsor, and institutional review board were found to be 15 (37.5%), 13 (32.5%), 21 (52.5%), and 10 (25.0%), respectively. The exclusion of patients from the review objective due to serious violations of GCP in 40 audits for oncology drug applications was observed in 2 (5.0%) cases, whereas that in the remaining 343 audits for other drug applications was observed in 40 (11.7%) cases. CONCLUSION: The overall compliance of GCP in oncology registration trials was moderately better than that in registration trials for other diseases, although there was no statistically significant difference between them.

EMX2 is epigenetically silenced and suppresses growth in human lung cancer.

Lung cancer is a common cancer and the leading cause of cancer-related death worldwide. Aberrant activation of WNT signaling is implicated in lung carcinogenesis. EMX2, a human homologue of the Drosophila empty spiracles gene is a homeodomain-containing transcription factor. The function of EMX2 has been linked to the WNT signaling pathway during embryonic patterning in mice. However, little is known about the role of EMX2 in human tumorigenesis. In this study, we found that EMX2 was dramatically downregulated in lung cancer tissue samples and this downregulation was associated with methylation of the EMX2 promoter. Restoration of EMX2 expression in lung cancer cells lacking endogenous EMX2 expression suppressed cell proliferation and invasive phenotypes, inhibited canonical WNT signaling, and sensitized lung cancer cells to the treatment of the chemo cytotoxic drug cisplatin. On the other hand, knockdown of EMX2 expression in lung cancer cells expressing endogenous EMX2 promoted cell proliferation, invasive phenotypes and canonical WNT signaling. Taken together, our study suggests that EMX2 may have important roles as a novel suppressor in human lung cancer.

Magnetic separation and characterization of keratinocyte stem cells from human gingiva.

BACKGROUND AND OBJECTIVE: Although keratinocyte stem cells play a key role in tissue homeostasis, wound healing and neoplasia, they remain difficult to identify and characterize. The purpose of this study was to isolate and characterize an oral keratinocyte stem-cell population. MATERIAL AND METHODS: Oral human keratinocytes obtained from keratinized oral mucosa were magnetically separated using α(6) ß(4) integrin and a proliferation-related marker, CD71. The isolated cell fractions were analyzed for cell size, cell cycle stage (using flow cytometry) and colony-forming ability. The expression of stem cell markers p63 and cytokeratin 19 and of differentiation markers cytokeratin 10 and involucrin was checked using immunocytochemical analysis. RESULTS: The stem cell CD71(neg) fraction had the smallest cell size compared with CD71(pos) and fractions [780.7 ± 141.5 (pixels), 1422.9 ± 264.6 (pixels) and 3844.4 ± 220.1 (pixels) respectively, p < 0.01; analysis of variance (ANOVA)]. Also, the CD71(neg) subpopulation consistently had the highest colony-forming ability among the three cell fractions (126.2 ± 21.7 vs. 32.8 ± 4.5 vs. 12.4 ± 2.1 compared with CD71(pos) and subpopulations, respectively, p < 0.01; ANOVA). Moreover, the CD71(neg) fraction contained more quiescent cells and fewer actively cycling cells than the CD71(pos) cell fraction. The candidate stem cells were positive for cytokeratin 19 and p63 keratinocyte stem cell markers, while differentiation markers such as cytokeratin 10 or involucrin were absent. CONCLUSION: The human gingival CD71(neg) cell fraction, separated by a magnetic system, demonstrated several characteristics of gingival keratinocyte stem cells. It is also suggested that a magnetic system may be an important tool in acquiring oral keratinocyte stem cells for research.

Prediction of progressive disease using tumor markers in metastatic breast cancer patients without target lesions in first-line chemotherapy.

BACKGROUND: The aim of this study was to develop a prediction model of progressive disease (PD) in breast cancer patients without measurable disease in first-line chemotherapy. METHODS: We developed a model to predict PD using carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 15-3 in metastatic breast cancer patients who were enrolled in a phase III trial. The model was determined using the area under the receiver operating characteristic curve (AUC) calculated by the bootstrap method as internal validation. We verified the model for those who received first-line chemotherapy in a clinical setting as external validation. We categorized patients without measurable disease into PD and non-PD groups and compared the time to progression (TTP). RESULTS: The model consisted of percent changes in CEA and CA 15-3 levels from second to third chemotherapy course and baseline abnormality of them. The AUC after external validation was 0.90. Patients without measurable disease were categorized into PD (N = 10) and non-PD groups (N = 53) by the model. The difference in TTP between the two groups was statistically significant (hazard ratio, 0.437; P = 0.021). CONCLUSION: The model may be useful to determine PD in metastatic breast cancer patients without measurable disease.

Change in the hormone receptor status following administration of neoadjuvant chemotherapy and its impact on the long-term outcome in patients with primary breast cancer.

BACKGROUND: To evaluate the impact of change in the hormone receptor (HR) status (HR status conversion) on the long-term outcomes of breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: We investigated 368 patients for the HR status of their lesions before and after NAC. On the basis of the HR status and the use/non-use of endocrine therapy (ET), the patients were categorised into four groups: Group A, 184 ET-administered patients with HR-positive both before and after NAC; Group B, 47 ET-administered patients with HR status conversion; Group C, 12 ET-naive patients with HR status conversion; Group D, 125 patients with HR-negative both before and after NAC. RESULTS: Disease-free survival in Group B was similar to that in Group A (hazard ratio, 1.16; P=0.652), but that in Group C was significantly lesser than that in Group A (hazard ratio, 6.88; P<0.001). A similar pattern of results was obtained for overall survival. CONCLUSION: Our results indicate that the HR status of tumours is a predictive factor for disease-free and overall survival and that ET appears to be suitable for patients with HR status conversion. Therefore, both the CNB and surgical specimens should be monitored for HR status.