1.A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min KIM ; Kyong Hwa PARK ; Yun Suk YU ; Ju Won KIM ; Jin Young PARK ; Kyunghee PARK ; Jong-Han YU ; Jeong Eon LEE ; Sung Hoon SIM ; Bo Kyoung SEO ; Jin Kyeoung KIM ; Eun Sook LEE ; Yeon Hee PARK ; Sun-Young KONG
Cancer Research and Treatment 2024;56(4):1113-1125
Purpose:
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods:
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results:
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
2.Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/TripleNegative Breast Cancer Patients With Excellent Response
Jai Min RYU ; Hyunjun LEE ; Wonshik HAN ; Han-Byoel LEE ; Sung Gwe AHN ; Hee Jeong KIM ; Hyung Seok PARK ; Ji Soo CHOI ; Haeyoung KIM ; Won Kyung CHO ; Jeong Eon LEE
Journal of Breast Cancer 2024;27(2):130-140
Purpose:
The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT.
Methods
ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1–3N0–1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life.Discussion: Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients.
3.Oncologic Outcomes of Immediate Breast Reconstruction in the Setting of Neoadjuvant Chemotherapy: A Long-term Follow-up Study of a Matched Cohort
Dong Seung SHIN ; Yoon Ju BANG ; Joon Young CHOI ; Sung Yoon JANG ; Hyunjun LEE ; Youngji KWAK ; Byung Joo CHAE ; Jonghan YU ; Jeong Eon LEE ; Seok Won KIM ; Seok Jin NAM ; Byung-Joon JEON ; Jai Kyong PYON ; Goo-Hyun MUN ; Kyeong-Tae LEE ; Jai Min RYU
Journal of Breast Cancer 2024;27(1):14-26
Purpose:
Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT.
Methods:
In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes.
Results:
After propensity score matching, 95 patients who underwent IBR following SSM/ NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5–181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death.
Conclusion
Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.
4.Improvement of Transfusion Practice in Cardiothoracic Surgery Through Implementing a Patient Blood Management Program
Hee Jung KIM ; Hyeon Ju SHIN ; Suk Woo LEE ; Seonyeong HEO ; Seung Hyong LEE ; Ji Eon KIM ; Ho Sung SON ; Jae Seung JUNG
Journal of Chest Surgery 2024;57(4):390-398
Background:
In this study, we examined the impact of a patient blood management (PBM) program on red blood cell (RBC) transfusion practices in cardiothoracic surgery.
Methods:
The PBM program had 3 components: monitoring transfusions through an order communication system checklist, educating the medical team about PBM, and providing feedback to ordering physicians on the appropriateness of transfusion. The retrospective analysis examined changes in the hemoglobin levels triggering transfusion and the proportions of appropriate RBC transfusions before, during, and after PBM implementation. Further analysis was focused on patients undergoing cardiac surgery, with outcomes including 30-day mortality, durations of intensive care unit and hospital stays, and rates of pneumonia, sepsis, and wound complications.
Results:
The study included 2,802 patients admitted for cardiothoracic surgery. After the implementation of PBM, a significant decrease was observed in the hemoglobin threshold for RBC transfusion. This threshold dropped from 8.7 g/dL before PBM to 8.3 g/dL during the PBM education phase and 8.0 g/dL during the PBM feedback period. Additionally, the proportion of appropriate RBC transfusions increased markedly, from 23.9% before PBM to 34.9% and 58.2% during the education and feedback phases, respectively. Among the 381 patients who underwent cardiac surgery, a significant reduction was noted in the length of hospitalization over time (p<0.001). However, other clinical outcomes displayed no significant differences.
Conclusion
PBM implementation effectively reduced the hemoglobin threshold for RBC transfusion and increased the rate of appropriate transfusion in cardiothoracic surgery. Although transfusion practices improved, clinical outcomes were comparable to those observed before PBM implementation.
5.Protective effect of platelet-rich plasma against cold ischemia-induced apoptosis of canine adipose-derived mesenchymal stem cells
Suji SHIN ; Sung-Eon KIM ; Seong-Won AN ; Seong-Mok JEONG ; Young-Sam KWON
Korean Journal of Veterinary Research 2024;64(1):e2-
This study was performed to assess the antiapoptotic effect of canine platelet-rich plasma (PRP) treated on the canine adipose-derived mesenchymal stem cells (cMSCs) under cold ischemic conditions. The effect of preventing apoptosis of cMSCs was evaluated in the apoptotic condition induced by cold ischemic injury in vitro. To determine the progression of apoptosis, the changes in cell nucleus were observed using 4',6-diamidino-2-phenylindole (DAPI) fluorescence staining. In addition, we examined the mitochondrial membrane potential (MMP) and caspase-3 activity. When the cold hypoxic injury was applied to cMSCs, the apoptotic change was observed by DAPI staining, mitochondrial staining for MMP, and caspase-3 assay. PRP significantly decreased the number of apoptotic cells. Nuclear shrinkage and fragmentation of apoptotic cells in control groups were observed by DAPI staining. The MMP was recovered by the treatment of PRP. In addition, when the luminescence intensity was measured for caspase-3 activity, the value was significantly higher in the PRP treated groups than the control groups. The results of this study showed that the PRP may have a beneficial effect on apoptosis induced by cold ischemic injury.
6.A Case of Endocrine Mucin-Producing Sweat Gland Carcinoma of the Eyelid
Ji Eon KANG ; Sung Eun KIM ; Suk-Woo YANG
Journal of the Korean Ophthalmological Society 2023;64(2):149-153
Purpose:
We report an endocrine mucin-producing sweat gland carcinoma diagnosed by biopsy in a patient who presented with an eyelid mass.Case summary: A 64-year-old male presented with a 3 × 3 mm solitary, painless pinkish mass on the right lower eyelid that had developed over the past year. The mass was excised and a biopsy was performed. The pathological findings included basaloid nodules composed of cells with eosinophilic cytoplasm, focal mucin production, and occasional glandular structures. Immunohistochemical examination was positive for cytokeratin 7 (CK-7), tumor protein 63 (P63), and the androgen receptor (AR). The patient was thus diagnosed with an endocrine mucin-producing sweat gland carcinoma. The lesion healed, and there has been no sign of recurrence over 6 months of follow-up.
Conclusions
An endocrine mucin-producing sweat gland carcinoma is a very rare low-grade glandular malignancy that has not been reported in Korea previously. The prognosis is good (i.e., there is no recurrence) when the lesion is completely surgically excised. We thought it would be useful to report this very rare case.
7.Epidemiology of Second Non-breast Primary Cancers among Survivors of Breast Cancer: A Korean Population–Based Study by the SMARTSHIP Group
Haeyoung KIM ; Su SSan KIM ; Ji Sung LEE ; Jae Sun YOON ; Hyun Jo YOUN ; Hyukjai SHIN ; Jeong Eon LEE ; Se Kyung LEE ; Il Yong CHUNG ; So-Youn JUNG ; Young Jin CHOI ; Jihyoung CHO ; Sang Uk WOO ;
Cancer Research and Treatment 2023;55(2):580-591
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.
8.Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study forOutcomes in Patients with Chronic Kidney Disease) cohort
Hyunsuk KIM ; Joongyub LEE ; Gwang Ho CHOI ; Hae Min JEONG ; Seok hyung KIM ; Jae Eon GU ; Jeong-Ju YOO ; Miyeun HAN ; Hyo-Jin KIM ; Su-Ah SUNG ; Seung Hyeok HAN ; Yeong Hoon KIM ; Jong-Woo YOON ; Jongho HEO ; Kook-Hwan OH
Kidney Research and Clinical Practice 2022;41(1):43-57
Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs). Methods: The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined. Results: Among all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant. Conclusion: Socioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs.
9.Annular Pancreas: A Rare Cause of Upper Gastrointestinal Bleeding in Adults
Joung Ah KWEUN ; Hyung Mook KANG ; Jang Eon KIM ; Sung Jae PARK
The Korean Journal of Gastroenterology 2022;79(4):182-186
Annular pancreas is a rare congenital anomaly in which a thin band of pancreatic tissue partially or completely surrounds the duodenum.It is challenging to diagnose due to its variable clinical presentation. Approximately two-thirds of patients have no symptoms in their lifetime, and most symptomatic cases are seen in neonates and infants. Symptomatic adult patients present with upper gastrointestinal symptoms, such as epigastric pain, vomiting, and postprandial fullness associated with gastric outlet obstruction. Complications associated with annular pancreas include peptic ulcer disease, pancreatitis, pancreatic head carcinoma, and biliary obstruction. Annular pancreas is also a rare cause of upper gastrointestinal bleeding in adults, but it should be considered as one of the differential diagnoses in patients presenting with a peptic ulcer and duodenal stricture. Here, we report the case of a 60-year-old man who presented with melena and was subsequently diagnosed with an annular pancreas.
10.Comprehensive clinical characterization of patients with BRCA1: c.5017_5019del germline variant
Yoon Ju BANG ; Won Kyung KWON ; Jong-Won KIM ; Jeong Eon LEE ; Boo Yeon JUNG ; Mina KIM ; Jisun KIM ; Jeongshin AN ; Seung Pil JUNG ; Hong-Kyu KIM ; Zisun KIM ; Hyun Jo YOUN ; Jai Min RYU ; Sung-Won KIM ;
Annals of Surgical Treatment and Research 2022;103(6):323-330
Purpose:
We provide evidence for the reclassification of the BRCA1:c.5017_5019del variant by presenting the clinicopathological characteristics, clinical outcomes, and family history of breast or ovarian cancer in 17 patients with this variant.
Methods:
This study included breast or ovarian cancer patients tested for BRCA1/2 genes between January 2008 and June 2020 at 10 medical centers in Korea. We retrospectively reviewed 17 probands from 15 families who had the BRCA1:c.5017_5019del variant according to the electronic medical records.
Results:
We present 10 breast cancer patients and 7 ovarian cancer patients from 15 families identified as having BRCA1:c.5017_5019del and a total of 19 cases of breast cancer and 14 cases of ovarian cancer in these families. The ratio of breast-to-ovarian cancer was 1.3:1. Breast cancer patients with this variant showed a rich family history of breast or ovarian cancer, 8 patients (80.0%). The mean age at diagnosis was 45.4 years and 6 patients (60.0%) were categorized into hormone-receptor–negative breast cancer. Also, the ovarian cancer patients with this variant showed strong family histories of breast and/or ovarian cancer in 4 patients (57.1%).
Conclusion
We presented clinical evidence for the reclassification of BRCA1:c.5017_5019del as a likely pathogenic variant (LPV). Reclassification as LPV could result in the prophylactic treatment and medical surveillance of probands, family testing recommendations, and appropriate genetic counseling of their families.

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