ABSTRACT
Background@#Carvedilol is a beta-adrenergic receptor antagonist primarily metabolized by cytochromes P450 (CYP) 2D6. This study established a carvedilol population pharmacokinetic (PK)–pharmacodynamic (PD) model to describe the effects of CYP2D6 genetic polymorphisms on the inter-individual variability of PK and PD. @*Methods@#The PK–PD model was developed from a clinical study conducted on 21 healthy subjects divided into three CYP2D6 phenotype groups, with six subjects in the extensive metabolizer (EM, *1/*1, *1/*2), seven in the intermediate metabolizer-1 (IM-1, *1/*10, *2/*10), and eight in the intermediate metabolizer-2 (IM-2, *10/*10) groups. The PK–PD model was sequentially developed, and the isoproterenol-induced heart rate changes were used to establish the PD model. A direct effect response and inhibitory E max model were used to develop a carvedilol PK–PD model. @*Results@#The carvedilol PK was well described by a two-compartment model with zeroorder absorption, lag time, and first-order elimination. The carvedilol clearance in the CYP2D6*10/*10 group decreased by 32.8% compared with the other groups. The inhibitory concentration of carvedilol estimated from the final PK–PD model was 16.5 ng/mL regardless of the CYP2D6 phenotype. @*Conclusion@#The PK–PD model revealed that the CYP2D6 genetic polymorphisms were contributed to the inter-individual variability of carvedilol PK, but not PD.
ABSTRACT
The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC 0-24 ) of 400 to 600 mg*h/L for serious methicillinresistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC 0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC 0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC 0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.
ABSTRACT
Purpose@#This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer. @*Materials and Methods@#Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis. @*Results@#The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02). @*Conclusion@#Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient’s age at IBC diagnosis, income level, and a receipt of systemic treatments.
ABSTRACT
Eighty-five Korean kidney transplant recipients who received three doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine were tested with anti-receptor binding domain (RBD) antibody and neutralizing antibody. High anti-RBD antibody (≥ 100 U/mL) and neutralizing antibody responses (≥ 30%) were detected in 51/85 (60.0%) patients.When we divided the patients with the time from transplantation to vaccination (< 1, 1–2.4, 2.5–4.9, and ≥ 5-year), anti-RBD antibody titers were 3.2 U/mL, 27.8 U/mL, 370.2 U/mL, and 5,094.2 U/mL (P < 0.001) and anti-neutralizing antibody levels were 2.2%, 11.6%, 45.6%, and 93.0% (P < 0.001), respectively. Multivariate analysis revealed increased antibody responses when the time from transplantation to vaccination was five years or longer (odds ratio, 12.0; confidence interval, 2.7–52.8). Korean kidney transplant recipients had suboptimal antibody responses after the third dose of SARS-CoV-2 vaccine. A shorter time from transplantation to vaccination was a risk factor for a low antibody response.
ABSTRACT
Purpose@#This study was conducted to investigate the trend of domestic medical travel from non-Seoul areas to Seoul for initial breast cancer treatment, and identify factors associated with medical travel in breast cancer patients. @*Methods@#A nationwide retrospective cohort study was performed using the Health Insurance Review and Assessment data of South Korea. Patients were classified according to the regions in which they underwent breast biopsy (Seoul vs.metropolitan cities vs. other regions). Frequencies of biopsy, diagnosis, treatment, and domestic medical travel were analyzed according to regions, and factors associated with medical travel were investigated. @*Results@#A total of 150,709 breast cancer survivors who were diagnosed between January 2010 and December 2017 were included. The total rate of medical travel from non-Seoul regions to Seoul had increased from 14.2% (1,161 of 8,150) in 2010 to 19.8% (2,762 of 13,964) in 2017. Approximately a quarter of patients from other regions traveled to Seoul, and over 40% of patients from Chungbuk, Gyeongbuk, and Jeju regions traveled to Seoul for initial treatment in 2017. The difference in the annual frequencies of upfront surgery between Seoul and non-Seoul regions increased over time. Younger age and regions other than metropolitan cities were significantly related to medical travel. Patients covered by medical aid or past medical histories were significantly less likely to travel to Seoul for initial breast cancer treatment. @*Conclusion@#Medical travel to Seoul for upfront breast cancer surgery is increasing. Policies for appropriate healthcare delivery need to be established in the near future.
ABSTRACT
Purpose@#This study aimed to analyze the waiting time for initial treatment after breast cancer diagnosis and determine the factors influencing treatment delay in South Korea. @*Methods@#This nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment data. The participants were classified according to the regions where their biopsy and treatment were performed (Seoul-Seoul, Metro-Metro, OtherOther, Metro-Seoul, Other-Seoul). Waiting time was analyzed according to regional subgroup, year of diagnosis, and type of treatment. Multivariable logistic regression models were constructed to identify the factors associated with treatment delay (after 30 days of diagnosis). @*Results@#A total of 133,514 participants newly diagnosed between January 2010 and December 2017 were included in the study. The median waiting time for initial treatment in the total population increased from 8 days, in 2010, to 14 days, in 2017. In the Seoul-Seoul group, the waiting time increased from 10 days, in 2010, to 16 days, in 2017. Although the median waiting time was approximately 10 days in the Metro-Metro and Other-Other groups, it was 27 and 24 days, in the Metro-Seoul and Other-Seoul group, respectively, in 2017. The proportion of delayed upfront surgery by more than 30 days was higher in the Metro-Seoul (odds ratio [OR], 8.088; 95% confidence interval [CI], 7.357–8.893; p < 0.001) and OtherSeoul (OR, 6.210; 95% CI, 5.717–6.750; p < 0.001) groups than in the Metro-Metro (OR, 1.468; 95% CI, 1.352–1.594; p < 0.001) and Other-Other (reference) groups. Previous medical history and treatment at tertiary hospital were observed as factors related to delayed surgery. @*Conclusion@#Waiting times for breast cancer surgery have increased across all regions of Korea, with those traveling to Seoul experiencing particularly long wait times.
ABSTRACT
OBJECTIVE@#To analyze the available data on the anti-anger effects of herbal medicines (HMs) as well as their underlying mechanisms in rat models.@*METHODS@#From 6 electronic databases [PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang, Oriental Medicine Advanced Searching Integrated System (OASIS), and Research Information Sharing Service (RISS)], relevant animal experiments were searched by using "anger," "rats," and "animal" as search keywords. The last search was conducted on November 22, 2019, and all experiments involving rat models of anger and treatment using HMs published until the date of the search were considered.@*RESULTS@#A total of 24 studies with 16 kinds of HMs were included. Most studies have used the "tail irritating method" and "social isolation and resident intruder" method to establish anger models. According to the included studies, the therapeutic mechanisms of HMs for anger regulation and important herbs by their frequency and/or preclinical evidence mainly incladed regulation of hemorheology (Bupleuri Radix, Paeoniae Radix Alba, and Glycyrrhizae Radix), regulation of sex hormones (Bupleuri Radix, Cyperi Rhizoma, and Paeoniae Radix Alba), regulation of neurotransmitters (Cyperi Rhizoma), regulation of anger-related genes (Bupleuri Radix, Glycyrrhizae Radix, and Paeoniae Radix Alba), and other effects. Overall, Liver (Gan) qi-smoothing herbs including Bupleuri Radix and Cyperi Rhizoma were the most frequently used.@*CONCLUSIONS@#This review found the frequent methods to establish an anger model, and major mechanisms of anti-anger effects of HMs. Interestingly, some Liver qi-smoothing herbs have been frequently used to investigate the anti-anger effects of HM. These findings provide insight into the role and relevance of HMs in the field of anger management.
Subject(s)
Animals , Rats , Anger , Drugs, Chinese Herbal/therapeutic use , Herbal Medicine , Medicine, Chinese Traditional , Paeonia/chemistryABSTRACT
The primary healing potential of anterior cruciate ligament (ACL) has been reported to be extremely poor in clinical and experimental studies. Most authors believe that the ACL does not heal spontaneously after rupture. In 1998, Kurosaka et al. reported two cases of a spontaneously healed torn ACL after non-surgical treatment; only a few cases have been reported. There are some reports of the spontaneously healed ACL or good clinical results after an ACL rupture in a conservative treatment group, but most studies were done by follow-up MRI or the clinical scores. This study experienced a case of spontaneous healing of a ruptured ACL confirmed by magnetic resonance imaging and arthroscopy. This paper reports a case with a review of the literature.
ABSTRACT
Trimethylamine N-oxide (TMAO) is a small molecular amine oxide generated from dietary choline and carnitine through intestinal microbial metabolism. Recently, TMAO has attracted much public attention as its role in disease progression has been proven in many clinical studies. The plasma concentration of TMAO in humans was found to be positively associated with the increased risk of many diseases including cardiovascular diseases and chronic kidney diseases. To achieve accurate and sensitive quantitation of TMAO for clinical applications, we established and validated a simple quantitative method using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. We constructed an eight-point calibration curve in an artificial surrogate matrix instead of the commonly used biological matrices to avoid interference from the endogenous TMAO. The calibration curve showed excellent linearity in the range of 1 to 5,000 ng/mL, with a correlation coefficient (R2 ) higher than 0.996 in each validation batch. Moreover, both the intra-day and inter-day assays achieved satisfactory precision and accuracy results ranging from 1.65–7.15% and 96.36–111.43%, respectively. Further, this method was cross-validated using a human plasma matrix and applied to a clinical pharmacology study. Overall, these results demonstrate that the developed quantitation method is applicable in clinical research for monitoring disease progression and evaluating drug effects.
ABSTRACT
This study evaluated the incidence, the survival outcomes and its prognostic factors for male breast cancer (MBC) in Korea. Using the National Health Insurance Service database of Korea, we identified MBC patients who had the new claim code of C50. Medical records including type of surgeries and radiotherapy within one year of the first claim and death records were reviewed. Between 2005 and 2016, 838 newly diagnosed MBC patients were included (median follow-up, 1,769 days). The 70–74-year age group had the highest incidence of MBC. The 5-year survival rate was 73.7%. Age > 65 years, low income, no surgical intervention, no tamoxifen use, and > 2 comorbidities correlated with a worse outcome. MBC incidence has increased over time, and its peak is noted at age > 70 years. Age > 65 years, > 2 comorbidities, no surgical intervention, and no tamoxifen use correlate to poor prognosis.
ABSTRACT
Purpose@#The tumor-infiltrating lymphocytes (TILs) expression in breast cancer is a positive prognostic marker for certain breast cancer subtypes. We evaluated the efficacy of dual antihuman epidermal growth factor receptor 2 (HER2) blockade in HER2-positive breast cancer and hypothesized that high TILs tumors are associated with better outcomes. @*Methods@#A total of 176 patients who were treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) between December 2015 and December 2018 were reviewed. They were grouped based on a cut-off value of the stromal TILs grade (≤ 20% TILs, > 20% TILs). @*Results@#In total, 107 patients (60.8%) achieved pathological complete response (pCR).Hormone receptor (HR)-negativity (p = 0.001) and a high TILs grade (p = 0.022) were independent predictors of pCR. Among the HR-negative patients, high TILs tumors were significantly associated with pCR (p = 0.035). @*Conclusion@#HR status and the TILs grade are significantly correlated with pCR in dual anti-HER2 neoadjuvant therapy. The evaluation of the TILs at baseline may be beneficial for predicting pCR in HER2-positive breast cancer.
ABSTRACT
Purpose@#The tumor-infiltrating lymphocytes (TILs) expression in breast cancer is a positive prognostic marker for certain breast cancer subtypes. We evaluated the efficacy of dual antihuman epidermal growth factor receptor 2 (HER2) blockade in HER2-positive breast cancer and hypothesized that high TILs tumors are associated with better outcomes. @*Methods@#A total of 176 patients who were treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) between December 2015 and December 2018 were reviewed. They were grouped based on a cut-off value of the stromal TILs grade (≤ 20% TILs, > 20% TILs). @*Results@#In total, 107 patients (60.8%) achieved pathological complete response (pCR).Hormone receptor (HR)-negativity (p = 0.001) and a high TILs grade (p = 0.022) were independent predictors of pCR. Among the HR-negative patients, high TILs tumors were significantly associated with pCR (p = 0.035). @*Conclusion@#HR status and the TILs grade are significantly correlated with pCR in dual anti-HER2 neoadjuvant therapy. The evaluation of the TILs at baseline may be beneficial for predicting pCR in HER2-positive breast cancer.
ABSTRACT
Cytochrome P450 (CYP) 3A enzymes, the most important phase 1 drug-metabolizing enzymes, are responsible for 50% of the metabolism of clinically used drugs. CYP3A activity varies widely among individuals, which can affect the probability of adverse drug reactions and drug-drug interactions mediated by the induction or inhibition of the enzyme. Hence, it is important to be able to predict CYP3A activity in individuals to reduce the incidence of unexpected drug responses. To specifically and quickly measure CYP3A activity, we developed method based on gas chromatography interfaced with triple-quadrupole mass spectrometry for the quantification of cortisol, cortisone, 6β-hydroxycortisol, and 6β-hydroxycortisone simultaneously in urine and 4β-hydroxycholesterol in plasma. The results were calculated based on charcoal-stripped steroid-free urine and plasma control samples. The accuracy and precision were 93.18% to 110.0% and 1.96% to 5.34%, respectively. This method was then applied to measure endogenous steroids from urine and plasma samples of healthy Korean males and females. The calibration curves of all analytes showed good linearity with a correlation coefficient (r2) that ranged from 0.9953 to 0.9999. Therefore, this validated method can be used to measure endogenous biomarkers to predict CYP3A activity and might be applicable in the prediction of CYP3A-mediated drug interactions of new drug candidates.
ABSTRACT
Purpose@#This study examined the association between fruit and vegetable intake and mental health in Korean adolescents. @*Methods@#This study used the data from the 2014–2017 Korea Youth Risk Behavior Survey, a national cross-sectional survey on 137,101 boys and 130,806 girls aged 12–18. Fruit and vegetable intake was assessed based on the frequency of consumption. The outcome variables were the perceived happiness, perceived stress, depressive symptom and suicidal ideation over the previous 12 months. Logistic regression models were used after adjusting for the demographic, life style and other dietary factors. @*Results@#Only 34% and 29% of Korean adolescents consumed fruits more than 5 times/ week and vegetables more than 2 times/day, respectively; whereas 37%, 25% and 12.2% of Korean adolescents had perceived stress, depressive symptom and suicidal ideation, respectively. After adjusting for the confounding variables, the greater consumption of fruit and vegetable were all associated with a higher odds of perceived happiness; the adjusted odds ratios (AORs) (95% CI) were 1.53 (1.46–1.60) in boys and 1.82 (1.73–1.90) in girls who consumed fruit ≥ 5 times/week, and 1.65 (1.54–1.76) in boys and 1.62 (1.51–1.72) in girls who consumed vegetable ≥ 2 times/day. In contrast, the consumption of fruit or vegetable were all significantly associated with a lower odds of perceived stress, depressive symptom, and suicidal ideation; the AOR (95% CI) were 0.70 (0.67–0.73), 0.88 (0.84–0.93), and 0.78 (0.73– 0.83) in boys who consumed fruit 3–4 times/week, and 0.71 (0.67–0.76), 0.88 (0.81–0.94), and 0.68 (0.62–0.74) in boys who consumed vegetable 5–7 times/week. Similar associations of fruit or vegetable consumption with perceived stress, depressive symptom, or suicidal ideation were found in girls. @*Conclusion@#These findings provide evidence that increasing fruit and vegetable intake is important for better mental health among adolescents.
ABSTRACT
The combination of luteinizing hormone-releasing hormone analogs (LHRHa) with tamoxifen is used as a standard postoperative adjuvant therapy in patients with hormone receptor-positive/premenopausal breast cancer. Long-acting LHRHa formulations offer advantages in terms of patient convenience. However, data on the effectiveness of the 3-month (3M) acting formulation are still insufficient. This study was performed on patients who received the 3M LHRHa after surgery. The serum estradiol (E2) and follicle-stimulating hormone levels were measured before surgery, and periodically after surgery. In total, 318 patients were included in the study and analyzed. The mean E2 level before surgery was 63.7 pg/mL, while the mean E2 level during the administration of 3M LHRHa was 4.9 pg/mL.None of the patients were menstruating and had E2 values above 30.0 pg/mL. It is thought that the 3M LHRHa formulation can suppress the ovarian function effectively and be safely used to improve compliance.
ABSTRACT
Purpose@#Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. @*Methods@#RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. @*Results@#Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. @*Conclusion@#Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.
ABSTRACT
OBJECTIVE@#To investigate the clinical efficacy and safety of miniscalpel-needle (MSN) treatment for tension-type headache (TTH).@*METHOD@#Seven medical databases were searched to identify randomized controlled trials (RCTs) evaluating the effect and safety of MSN treatment. All articles published up to November 15, 2018 were retrieved. A meta-analysis was conducted for the included studies, and the risk of bias was assessed. Primary outcomes were visual analogue scale (VAS) or numeric rating scale (NRS) score. Secondary outcomes were clinical effective rates including total effective rate (TER), markedly effective rate (MER), and totally cured rate (TCR) determined by improvement in clinical symptoms or VAS scores, the frequency of adverse events (AEs) that occurred during the study, and participant quality of life (QOL).@*RESULTS@#Seven RCTs involving 724 participants were included. MSN treatment showed significantly higher MER and TCR [relative risk (RR) 1.27, 95% confidence interval (CI) 1.01 to 1.61; RR 1.31, 95% CI 1.09 to 1.57, respectively], but not TER (RR 1.03, 95% CI 0.96 to 1.10) compared to acupuncture. MSN treatment plus conventional treatment showed significant lower VAS and higher TER, MER, and TCR (mean difference -3.54, 95% CI -3.80 to -3.28; RR 1.14, 95% CI 1.06 to 1.23; RR 2.31, 95% CI 1.50 to 3.58; RR 3.01, 95% CI 2.25 to 4.02, respectively) compared to conventional treatment.@*CONCLUSIONS@#According to current evidence, MSN treatment as a monotherapy or as an adjunctive treatment to other existing treatments might have benefits on treating TTH. However, since the number and the sample size of studies included were both small and the methodological quality was poor, the findings of this review should be interpreted with great caution, and our confidence in the results is low. A high quality RCT using objective outcomes should be performed on this topic.
ABSTRACT
The combination of luteinizing hormone-releasing hormone analogs (LHRHa) with tamoxifen is used as a standard postoperative adjuvant therapy in patients with hormone receptor-positive/premenopausal breast cancer. Long-acting LHRHa formulations offer advantages in terms of patient convenience. However, data on the effectiveness of the 3-month (3M) acting formulation are still insufficient. This study was performed on patients who received the 3M LHRHa after surgery. The serum estradiol (E2) and follicle-stimulating hormone levels were measured before surgery, and periodically after surgery. In total, 318 patients were included in the study and analyzed. The mean E2 level before surgery was 63.7 pg/mL, while the mean E2 level during the administration of 3M LHRHa was 4.9 pg/mL.None of the patients were menstruating and had E2 values above 30.0 pg/mL. It is thought that the 3M LHRHa formulation can suppress the ovarian function effectively and be safely used to improve compliance.
ABSTRACT
Purpose@#Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. @*Methods@#RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. @*Results@#Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. @*Conclusion@#Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.
ABSTRACT
PURPOSE: Discontinuation of hormone therapy is known to lead to a poorer prognosis in breast cancer patients. We aimed to investigate the prescription gap as a prompt index of medication adherence by using prescription data extracted from patient electronic medical records. METHODS: A total of 5,928 patients diagnosed with invasive, non-metastatic breast cancer, who underwent surgery from January 1, 1997 to December 31, 2009, were enrolled retrospectively. The prescription data for 4.5 years of hormonal treatment and breast cancer-related events after treatment completion were analyzed. We examined the characteristics and prognoses of breast cancer in patients with and without a 4-week gap. RESULTS: Patients with a gap showed a significantly higher risk of breast cancer recurrence, distant metastasis, breast cancer-specific death, and overall death after adjustment (hazard ratio [HR], 1.389; 95% confidence interval [CI], 1.089–1.772; HR, 1.568; 95% CI, 1.158–2.123; HR, 2.108; 95% CI, 1.298–3.423; and HR, 2.102; 95% CI, 1.456–3.034, respectively). When patients were categorized based on gap summation, the lower third (160 days) and fourth (391 days) quartiles showed a significantly higher risk of distant metastasis (HR, 1.758; 95% CI, 1.186–2.606 and HR, 1.844; 95% CI, 1.262–2.693, respectively). CONCLUSION: A gap of > 4 weeks in hormonal treatment has negative effects on breast cancer prognosis, and can hence be used as a sentinel index of higher risk due to treatment non-adherence. Further evaluation is needed to determine whether the gap can be used as a universal index for monitoring the adherence to hormonal treatment.