A Comprehensive Analysis of HOXB13 Expression in Hepatocellular Carcinoma.

Background and objectives: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is caused by multiple factors. To explore novel targets for HCC treatment, we comprehensively analyzed the expression of HomeoboxB13 (HOXB13) and its role in HCC. Materials and Methods: The clinical significance of HCC was investigated using open gene expression databases, such as TIMER, UALCAN, KM, OSlihc, and LinkedOmics, and immunohistochemistry analysis. We also analyzed cell invasion and migration in HCC cell lines transfected with HOXB13-siRNA and their association with MMP9, E2F1, and MEIS1. Results: HOXB13 expression was higher in fibrolamellar carcinoma than in other histological subtypes. Its expression was associated with lymph node metastasis, histological stage, and tumor grade. It was positively correlated with immune cell infiltration of B cells (R = 0.246), macrophages (R = 0.182), myeloid dendritic cells (R = 0.247), neutrophils (R = 0.117), and CD4+ T cells (R = 0.258) and negatively correlated with immune cell infiltration of CD8+ T cells (R = -0.107). A positive correlation was observed between HOXB13, MMP9 (R = 0.176), E2F1 (R = 0.241), and MEIS1 (R = 0.189) expression (p < 0.001). The expression level of HOXB13 was significantly downregulated in both HepG2 and PLC/PFR/5 cell lines transfected with HOXB13-siRNA compared to that in cells transfected with NC siRNA (p < 0.05). Additionally, HOXB13 significantly affected cell viability and wound healing. Conclusions: HOXB13 overexpression may lead to poor prognosis in patients with HCC. Additional in vivo studies are required to improve our understanding of the biological role and the exact mechanism of action of HOXB13 in HCC.

The efficacy and safety of an indocyanine green-hyaluronic acid mixture (LuminoMark™) for localization in patients with non-palpable breast lesions: A multicenter, randomized, open-label, parallel phase 3 clinical trial.

Purpose: The incidence of early tumor detection is increasing due to popularization of breast cancer screening and the development of imaging techniques. Thus, suitable preoperative localization is required for proper diagnosis and treatment of non-palpable breast lesions. The purpose of this study was to evaluate the efficacy and safety of indocyanine green (ICG)-hyaluronic acid (HA) mixture for lesion localization compared to activated charcoal. Methods: This was a multicenter, randomized, open-label, parallel phase 3 clinical trial performed at four centers in Korea. Female patients scheduled for surgery to remove non-palpable breast lesions were enrolled. One hundred and nine patients were randomly assigned to a control group (activated charcoal: 0.3. - 1 mL) or a study group (ICG-HA mixture, 0.2 mL) for the localization of a breast lesion. The primary endpoint was the accuracy of resection. Secondary endpoints included the technical success rate, histopathological accuracy, skin pigmentation rate, and adverse event rate. Results: A total of 104 patients were eligible for per-protocol analysis (control group, n = 51; study group, n = 53). The accuracy of resection in the study group was not inferior to that of the control group (90.57% vs. 98.04%, 95% confidence interval (CI): -2.31 - 18.91, p = 0.21). There was no statistically significant difference in technical success rate between the two groups (marking on breast skin: p = 0.11, marking on the excised specimen: p = 0.12). However, there were statistically significant differences in histopathological accuracy (0.26 ± 0.13 vs. 0.33 ± 0.17, p = 0.01) and skin pigmentation rate (0.00% vs. 30.77%, p< 0.01). Adverse events were not reported in either group. Conclusions: When localization was performed using ICG-HA, the accuracy of resection was not inferior to that of activated charcoal. However, skin pigmentation rate was significantly lower. In conclusion, ICG-HA is effective and safe for localizing of non-palpable breast lesions.

An induced annual modulation signature in COSINE-100 data by DAMA/LIBRA's analysis method.

The DAMA/LIBRA collaboration has reported the observation of an annual modulation in the event rate that has been attributed to dark matter interactions over the last two decades. However, even though tremendous efforts to detect similar dark matter interactions were pursued, no definitive evidence has been observed to corroborate the DAMA/LIBRA signal. Many studies assuming various dark matter models have attempted to reconcile DAMA/LIBRA's modulation signals and null results from other experiments, however no clear conclusion can be drawn. Apart from the dark matter hypothesis, several studies have examined the possibility that the modulation is induced by variations in detector's environment or their specific analysis methods. In particular, a recent study presents a possible cause of the annual modulation from an analysis method adopted by the DAMA/LIBRA experiment in which the observed annual modulation could be reproduced by a slowly varying time-dependent background. Here, we study the COSINE-100 data using an analysis method similar to the one adopted by the DAMA/LIBRA experiment and observe a significant annual modulation, however the modulation phase is almost opposite to that of the DAMA/LIBRA data. Assuming the same background composition for COSINE-100 and DAMA/LIBRA, simulated experiments for the DAMA/LIBRA without dark matter signals also provide significant annual modulation with an amplitude similar to DAMA/LIBRA with opposite phase. Even though this observation does not directly explain the DAMA/LIBRA results directly, this interesting phenomenon motivates more profound studies of the time-dependent DAMA/LIBRA background data.

Thorium and uranium trace ICP-MS analysis for AMoRE project.

AMoRE (Advanced Mo-based Rare process Experiment) is an international collaboration searching for the neutrinoless double-beta decay of the 100Mo isotope with cryogenic detectors using molybdate (100MoO4)-based scintillation crystals. The process requires that the detector apparatus and its components, including bolometric crystals and thus initial materials used for the crystal growth, be extremely low in radioactive isotopes having decays that may generate background noise signals in the region of interest. The present study summarizes an ICP-MS assay program conducted for the AMoRE experiment. Firstly, the 100MoO3 powder, the main component of the crystals, was studied in the analysis. Before crystal synthesis, enriched 100MoO3 powder was purified at the Center for Underground Physics (CUP). To ensure its radio purity, a sample preparation technique with a UTEVA® resin was developed for Th and U analysis with ICP-MS. The recovery yield was over 90% for the extraction procedure, and the detection limits for Th and U were 2.3 and 1.0 ppt, respectively. To determine the most appropriate material for the detector frame and shielding, several types of high-purity Cu were measured: Cu-OFE (Aurubis and Mitsubishi Materials) and Cu-NOSV (Aurubis). Similarly, a solid-phase extraction was applied for Th and U analysis, and detection limits were calculated at 0.1 and 0.2 ppt, respectively. The 3M Vikuiti™ ESR film, the closest part to the crystal in the detector assembly, was used as a light reflector. Two types of Vikuiti film, a roll and a sheet, were checked for radiopurity via full decomposition using a microwave ashing system. The procedural Detection Limits were achieved at a level of about 1 ppt.

Robot-assisted Nipple-sparing Mastectomy With Immediate Breast Reconstruction: An initial Experience of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).

OBJECTIVE: The aim of this study was to present the results of early experience of robot-assisted nipple sparing mastectomy (RANSM). BACKGROUND: RANSM improves cosmetic outcomes over conventional nipple-sparing mastectomy. However, data on the feasibility and safety of the RANSM are limited. METHODS: Patients who underwent RANSM with immediate breast reconstruction as part of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. clinicopathologic characteristics, perioperative complications, and operation time were collected. RESULTS: Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at 8 institutions. The median patient age was 45.5 years old (20-66 years), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage i, 11 cases were stage ii, and 4 cases were stage iii, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, 3 patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 12.0 days (5.0-24.0 days). The incision location was the mid-axillary line and the median incision length was 50.0 mm (30.0-60.0 mm). Median total operation time, median total mastectomy time, and median reconstruction time was 307.0 minutes (163.0-796.0 minutes), 189.5 minutes (97.5-325.0 minutes), and 119.5 minutes (45.0-689.0 minutes). Only 2 cases (2.5%) required reoperation. Nipple ischemia was found in 9 cases (10.9%) but only 1 case (1.2%) required nipple excision given that 8 cases (9.7%) resolved spontaneously. Skin ischemia was observed in 5 cases (6.1%) and only 2 (2.4%) cases needed skin excision whereas 3 cases (3.6%) resolved spontaneously. There was no conversion to open surgery orcases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). CONCLUSION: This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.

Strong constraints from COSINE-100 on the DAMA dark matter results using the same sodium iodide target.

We present new constraints on dark matter interactions using 1.7 years of COSINE-100 data. The COSINE-100 experiment, consisting of 106 kg of tallium-doped sodium iodide [NaI(Tl)] target material, is aimed to test DAMA's claim of dark matter observation using the same NaI(Tl) detectors. Improved event selection requirements, a more precise understanding of the detector background, and the use of a larger dataset considerably enhance the COSINE-100 sensitivity for dark matter detection. No signal consistent with the dark matter interaction is identified and rules out model-dependent dark matter interpretations of the DAMA signals in the specific context of standard halo model with the same NaI(Tl) target for various interaction hypotheses.

Systematic evaluation of scoring methods for Ki67 as a surrogate for 21-gene recurrence score.

Although Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath. We used OncotypeDx Recurrence Score (RS) as a benchmark to compare the potential clinical utility of each scoring methods. Both average and hotspot scores showed statistically significant but only modest correlation with OncotypeDx RS. Only hotspot score could meaningfully distinguish RS low-risk versus high-risk patients. However, hotspot score was less reproducible limiting its clinical utility. In summary, our data demonstrate that utility of the Ki67 labeling index is influenced by the choice of scoring method.

Rare case of postoperative mediastinitis following thyroidectomy.

Descending necrotizing mediastinitis (DNM) is a life-threatening complication secondary to oropharyngeal abscesses, cervical esophageal perforation, or neck infections spreading along the fascial planes into the mediastinum. Post-thyroidectomy surgical site infection is a highly unusual complication that is typically localized around the incision, but may be propagated into the mediastinum, causing DNM. We encountered a case of this rare complication after thyroidectomy. The patient was a 33-year-old woman who was admitted to our center for left hemithyroidectomy. The surgery was performed without any intraoperative events. However, she later developed fever, hypotension, and tachycardia. Imaging revealed deep neck emphysema and focal pneumomediastinum with infiltration in the anterior neck and mediastinum with abscess formation. Additional imaging at 7 days postoperatively revealed reduced fluid collection deep in the neck with minimal changes in fluid collection in the mediastinum. Esophageal perforation was excluded via an esophagogram, which lead to the conclusion that the infection may have been caused by open thyroidectomy. The patient was treated with prompt medical and surgical intervention. After treatment, she was discharged from the hospital with no further complications. We present our case report as well as a literature review of the diagnosis and treatment of this disease.

Prospective, Randomized, Comparative, Multicenter Study of the Hybrid Ultrasonic Advanced Bipolar Device and the Ultrasonic Coagulating Shears in Open Thyroidectomy.

Background. The hybrid ultrasonic advanced bipolar device (HUB) that integrates ultrasonic energy and advanced bipolar energy was recently developed and applied to thyroid surgery. The purpose of this study was to compare the efficacy and safety of HUB and ultrasonic coagulating shears for open thyroidectomy. Methods. A total of 200 patients were enrolled from April to September 2017 in this prospective, randomized, multicenter study. Patients were randomly assigned to an ultrasonic group (n = 101) or a hybrid group (n = 99). Results. Operation times were similar in the 2 study groups, that is, 54.2 ± 25.2 minutes in the ultrasonic group and 50.2 ± 21.6 minutes in the hybrid group. Postoperative surgical results and morbidities were no different in the 2 groups. However, the total amount of bleeding was significantly less in the hybrid group (13.0 ± 17.7 mg vs 8.6 ± 11.5 mg; P = .042). Conclusions. Our study showed that there was no significant difference between the 2 groups in postoperative surgical results and morbidity. The total bleeding amount was significantly less in the hybrid group. The study shows that HUB is comparable to the ultrasonic coagulating shears in terms of efficacy and safety during thyroid surgery.

A cryogenic setup for multifunctional characterization of luminescence and scintillation properties of single crystals.

This article reports on a cryogenic setup that can be used for multifunctional experimental purposes. The temperature of the setup can be set from 10 K to 300 K. Different kinds of experiments were carried out in this experimental setup such as (1) luminescence emission, light yield, and decay time measurement under excitation of 266 nm laser and 280 nm LED sources, (2) thermoluminescence (TL) measurement under an x-ray excitation source, (3) scintillation property measurements such as light output, energy resolution, and decay time under 137Cs (662 keV γ-rays) and 241Am (5.4 MeV α) isotope sources, and (4) scintillation measurement under a 90Sr beta source through the continuous single-photon counting technique. The luminescence and scintillation properties of various molybdate and tungstate crystals such as CaMoO4, Na2Mo2O7, Pb2MoO5, CdWO4, and ZnWO4 are characterized and reported in the present work. The TL measurement of a CaMoO4 crystal is carried out from 10 K to 300 K, and various kinetic parameters such as order of kinetics, frequency factor, activation energy, and figure of merit are calculated for different TL peaks. As the temperature goes down from room to 10 K, the light yield of all studied crystals increases. Since the light yield of the crystal increases as temperature decreases toward 10 K, this experimental setup can be used for the characterization of luminescence and scintillation properties of a single crystal for rare event searches such as neutrinoless double-beta decay and dark matter.

Clinicopathological Characteristics of PIK3CA Mutation and Amplification in Korean Patients with Breast Cancers.

The frequency of PIK3CA mutation and amplification was various and their clinical significances have not been clarified in Korean patients with invasive breast carcinoma (IBC). The study aimed to investigate the clinical and prognostic significances of PIK3CA mutation and amplification in IBC patients. DNA was isolated from paired normal and tumoral tissues in 128 IBC patients and the mutation and expression of PIK3CA gene were analyzed. PIK3CA mutation and expression was detected in 14.3% and 21.9% of IBC patients, respectively. And the level of PIK3CA expression was not different according to the presence of PIK3CA mutation (p = 0.775). PIK3CA mutation and expression were significantly associated with Luminal A type (p = 0.017 and p = 0.011, respectively). However, they did not have any clinical and prognostic values for IBC patients. This result suggested that alterations of PIK3CA pathway contribute to the pathogenesis of specific type of IBC.

Outcomes of Pregnancy after Breast Cancer in Korean Women: A Large Cohort Study.

PURPOSE: The purpose of this study was to determine the rate and outcomes of pregnancies subsequent to breast cancer in Korea, and the effect of such pregnancies on the prognosis of women who survived breast cancer and subsequently conceived. MATERIALS AND METHODS: We followed a total of 31,761 Korean women 45 years of age or younger who were treated for primary breast cancer from 2002 to 2010. We also included follow-up surveys that were conducted through December 2011. We identified recurrence and mortality from breast cancer using data linked to the Korea National Health Insurance database. We used propensity score matching of the study cohort to analyze the risks of recurrence and mortality from breast cancer depending on pregnancy. RESULTS: Within our sample, 992 women (3.1%) became pregnant after receiving treatment for breast cancer. Of those, 622 (67.5%) successfully delivered; the remaining 370 (32.5%) failed to deliver. After propensity score matching, we found that the women who became pregnant after breast cancer did not have a different risk of recurrence (hazard ratio [HR], 0.503; 95% confidence interval [CI], 0.434 to 0.584) and death (HR, 0.520; 95% CI, 0.397 to 0.681), compared with those who did not conceive after breast cancer treatment. CONCLUSION: Our study is the first to report outcomes for Korean women who survived breast cancer and subsequently conceived. Women who survived breast cancer and subsequently became pregnant did not show a poorer survival outcome, compared with those who did not become pregnant.

Measurement of Switching Performance of Pixelated Silicon Sensor Integrated with Field Effect Transistor.

Silicon shows very high detection efficiency for low-energy photons, and the silicon pixel sensor provides high spatial resolution. Pixelated silicon sensors facilitate the direct detection of low-energy X-ray radiation. In this study, we developed junction field effect transistors (JFETs) that can be integrated into a pixelated silicon sensor to effectively handle many signal readout channels due to the pixelated structure without any change in the sensor resolution; this capability of the integrated system arises from the pixelated structure of the sensor. We focused on optimizing the JFET's switching function, and simulated JFETs with different fabrication parameters. Furthermore, prototype JFET switches were designed and fabricated on the basis of the simulated results. It is important not only to keep the low leakage currents in the JFET but also reduce the current flow as much as possible by providing a high resistance when the JFET switch is off. We determined the optimal fabrication conditions for the effective switching of the JFETs. In this paper, we present the results of the measurement of the switching capability of the fabricated JFETs for various design variables and fabrication conditions.

TZAP Mutation Leads to Poor Prognosis of Patients with Breast Cancer †.

Background and Objectives: ZBTB48 is a telomere-associated factor that has been renamed as telomeric zinc finger-associated protein (TZAP). It binds preferentially to long telomeres, competing with telomeric repeat factors 1 and 2. Materials and Methods: We analyzed the TZAP mutation in 128 breast carcinomas (BCs). In addition, its association with telomere length was investigated. Results: The TZAP mutation (c.1272 G > A, L424L) was found in 7.8% (10/128) of the BCs and was associated with the N0 stage. BCs with the TZAP mutation had longer telomeres than those without this mutation. Survival analysis showed that the TZAP mutation resulted in poorer overall survival. Conclusions: These results suggest that the TZAP mutation is a possible prognostic marker in BC.

The Sentinel Lymph Node Biopsy Using Indocyanine Green Fluorescence Plus Radioisotope Method Compared With the Radioisotope-Only Method for Breast Cancer Patients After Neoadjuvant Chemotherapy: A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial.

BACKGROUND: This study aimed to compare the sentinel lymph node (SLN) identification rates for breast cancer patients after neoadjuvant chemotherapy (NAC) between the dual method (DM) of indocyanine green fluorescence (ICG-F) plus a radioisotope (RI) and RI alone. METHODS: This randomized study enrolled 130 patients who received NAC for breast cancer and 122 patients who received SLN biopsy (SLNB) using either DM (n = 58) or RI only (n = 64). The study compared the identification rate, number of SLNs, and detection time of SLNB. RESULTS: Among the 122 patients, 113 (92.6%) were clinically node-positive before NAC. The SLN identification rate was 98.3% in the DM group and 93.8% in the RI group (p = 0.14). The DM group and the RI group were similar in the average number of SLNs (2.2 ± 1.13 vs. 1.9 ± 1.33; p = 0.26) and the time to detection of the first SLN (8.7 ± 4.98 vs. 8.3 ± 4.31 min; p = 0.30). In the DM group, transcutaneous lymphatic drainage was visualized by fluorescence imaging for 65.5% (38 of 58) of the patients. The SLN identification rate was 94.7% using ICG-F and 93% using RI (p = 0.79). During and after the operation, no complications, including allergic reactions or skin necrosis, occurred. CONCLUSIONS: This study is the first randomized trial to use ICG-F for SLNB in breast cancer patients after NAC. The DM including ICG-F could be a feasible and safe method for SLNB in initially node-positive breast cancer patients with NAC.

Clinical and Prognostic Value of Human Mammary Tumor Virus in Korean Patients with Breast Carcinoma.

BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus, one of the causal agents of murine mammary tumors. Although HMTV has been frequently detected in human breast cancers, its clinical and prognostic value remains unknown. METHODS: In the present study, we analyzed HMTV infection using polymerase chain reaction (PCR) in 128 breast cancers. RESULTS: HMTV was found in 9.4% (12/128) of breast cancers and was significantly associated with breast pain (66.7% vs. 11.7%, p=0.007). It had a tendency to be detected more frequently in breast cancer patients with lower BMI<25, although this result was not statistically significant (18.8% vs. 5.4%, p=0.103). Kaplan-Meier survival analysis showed no prognostic value of HMTV in breast cancer (χ2=0.148, p=0.700). For the first time, we investigated the clinical and prognostic value of HMTV in Korean patients with breast cancer. CONCLUSION: Although our study revealed that HMTV infection does not have important clinical significance in breast cancer, the possibility remains that it may be a prominent causative agent of the disease.

Psychosocial Health of Disease-Free Breast Cancer Survivors Compared with Matched Non-cancer Controls.

PURPOSE: The present study investigated the psychosocial health of disease-free breast cancer survivors who receive health examinations compared to matched non-cancer controls in a community setting. MATERIALS AND METHODS: We used baseline data from the Health Examinee cohort, which is composed of subjects participating in health. The disease-free breast cancer survivors were defined as those who were ≥ 2 years from initial diagnosis of breast cancer who had completed treatment. Females without a history of cancer were randomly selected at 1:4 ratio by 5-year age groups, education, and household income as a comparison group. We analyzed results from the Psychosocial Well-being Index-Short Form (PWI-SF) as a psychosocial health measurement. RESULTS: A total of 347 survivors of breast cancer and 1,388 matched controls were included. Total scores on the PWI-SF were lower in breast cancer survivors than matched non-cancer controls (p=0.006), suggesting a lower level of psychosocial stress in breast cancer survivors. In comparison to the control group, prevalence of drinking, smoking and obesity were lower, while exercising for ≥ 150 min/wk was higher in breast cancer survivors (p < 0.05). These findings suggest that breast cancer survivors have better health behaviors than their noncancer controls. After adjusting for other sociodemographic variables, breast cancer survivors were 36% less likely to be included in the stress group (odds ratio, 0.64; 95% confidence interval, 0.42 to 0.98). CONCLUSION: The disease-free breast cancer survivors resuming daily life demonstrated better psychosocial health status compared to matched non-cancer controls.

Prognostic impact of skeletal muscle volume derived from cross-sectional computed tomography images in breast cancer.

PURPOSE: This study aimed to determine whether the prognosis of breast cancer is affected by muscle or fat volume as measured from computed tomography (CT) images. METHODS: We identified 1460 patients with chest CT who were diagnosed as having breast cancer at the National Cancer Center, Korea, between January 2001 and December 2009. Using CT images of 10-mm slices, we measured the cross-sectional areas of skeletal muscle and adipose tissue at the 3rd lumbar vertebrae, and derived their volumes. The skeletal muscle volume, fat volume, and muscle-to-fat ratio were evaluated for association with overall survival (OS) and recurrence-free survival (RFS). RESULTS: The median skeletal muscle and fat volumes among the patients were 93.3 cc (range 39.6-236.9) and 420.1 cc (range 19.5-1392.3), respectively. Patients with higher muscle volume had better prognosis than those with lower muscle volume [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.34-0.92, P = 0.022 for OS; HR 0.72, 95% CI 0.52-0.99, P = 0.046 for RFS]. However, body mass index (BMI) and fat volume were not associated with prognosis. In addition, muscle volume was a significant prognosticator for OS, regardless of BMI (HR 0.55, 95% CI 0.32-0.93, P = 0.034 in BMI < 25.0; HR 0.44, 95% CI 0.21-0.91, P = 0.026 in BMI ≥ 25.0). Among older patients (≥ 50), those with higher muscle volume showed better OS and RFS (HR 0.44, 95% CI 0.23-0.85, P = 0.015; HR 0.55, 95% CI 0.34-0.90, P = 0.017, respectively). CONCLUSION: This study demonstrated that breast cancer patients with higher skeletal muscle volume showed more favorable prognosis.

Oncologic Safety of Gonadotropin-Releasing Hormone Agonist for Ovarian Function Protection During Breast Cancer Chemotherapy.

BACKGROUND: Receipt of a gonadotropin-releasing hormone (GnRH) agonist has been reported to protect against ovarian failure. We sought to determine the oncologic effect of a GnRH agonist with chemotherapy for breast cancer patients. PATIENTS AND METHODS: Data from 1160 patients aged 20 to 40 years with stage I to III breast cancer who received chemotherapy from 5 hospitals in Korea from 2002 to 2012 were reviewed. A GnRH agonist was provided to 406 patients for ovarian protection during chemotherapy, and 754 patients received chemotherapy without ovarian protection. An individual score-matching strategy was used to create sets matched by age, tumor stage, hormone receptor status, neoadjuvant or adjuvant chemotherapy, and institute. RESULTS: Survival analysis by Cox regression showed that the GnRH agonist group had better distant metastasis-free survival (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.39-0.89) and disease-free survival (HR, 0.72; 95% CI, 0.52-0.99) than the chemotherapy-alone group. Among patients with hormone receptor-positive breast cancer, the benefit was significant for distant metastasis-free survival (HR, 0.53; 95% CI, 0.29-0.99) and disease-free survival (HR, 0.58; 95% CI, 0.35-0.96). CONCLUSION: Ovarian protection using a GnRH agonist can be safely considered for premenopausal breast cancer patients for whom chemotherapy is planned.

Use of adjuvant chemotherapy in hormone receptor-positive breast cancer patients with or without the 21-gene expression assay.

PURPOSE: We assessed the use of chemotherapy in breast cancer patients to investigate the factors that changed trends in chemotherapy following the adoption of the 21-gene expression assay in tumor genomic profiling. METHODS: Our study used 2033 patients from the National Cancer Center in Korea diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (tumor size of 0.5 cm or larger and 0-3 node metastases) from 2010 to 2015. We analyzed use of the 21-gene expression assay, changes in frequency of adjuvant chemotherapy use, and clinicopathological factors related to adjuvant chemotherapy to assess the impact of the 21-gene expression assay. RESULTS: Adjuvant chemotherapy use declined from 33.33% (2011) to 13.59% (2015) [relative risk (RR), 0.71; 95% CI 0.56-0.89; ptrend = 0.004] in patients with 21-gene expression assay data. Among patients without assay data, adjuvant chemotherapy use decreased from 76.79 to 40.17% between 2010 and 2015 (RR 0.87; 95% CI 0.84-0.91; ptrend < 0.001), especially for patients with node-negative/micrometastasis (RR 0.85; 95% CI 0.81-0.89; ptrend < 0.001). The frequency of adjuvant chemotherapy was significantly decreased after introduction of the 21-gene expression assay (p < 0.001). Tumor size (p < 0.001), progesterone receptor (PgR) status (p = 0.001), and proliferation index (Ki-67) levels (p < 0.001) were important factors for chemotherapy decision-making in node-negative/micrometastasis patients who did not undergo the assay. CONCLUSIONS: For HR-positive, HER2-negative breast cancer patients with 0-1 node metastases, chemotherapy use declined significantly after the adoption of the 21-gene assay. PgR status and Ki-67 were useful for chemotherapy decision-making in cases without the 21-gene assay.