1.Impact of HER2-Low Status on Pathologic Complete Response and Survival Outcome Among Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy
Young Joo LEE ; Tae-Kyung YOO ; Sae Byul LEE ; Il Yong CHUNG ; Hee Jeong KIM ; Beom Seok KO ; Jong Won LEE ; Byung Ho SON ; Sei Hyun AHN ; Hyehyun JEONG ; Jae Ho JUNG ; Jin-Hee AHN ; Kyung Hae JUNG ; Sung-Bae KIM ; Hee Jin LEE ; Gyungyub GONG ; Jisun KIM
Journal of Breast Cancer 2025;28(1):11-22
Purpose:
This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment.
Methods:
This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed.
Results:
Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953).
Conclusion
Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.
2.Impact of HER2-Low Status on Pathologic Complete Response and Survival Outcome Among Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy
Young Joo LEE ; Tae-Kyung YOO ; Sae Byul LEE ; Il Yong CHUNG ; Hee Jeong KIM ; Beom Seok KO ; Jong Won LEE ; Byung Ho SON ; Sei Hyun AHN ; Hyehyun JEONG ; Jae Ho JUNG ; Jin-Hee AHN ; Kyung Hae JUNG ; Sung-Bae KIM ; Hee Jin LEE ; Gyungyub GONG ; Jisun KIM
Journal of Breast Cancer 2025;28(1):11-22
Purpose:
This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment.
Methods:
This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed.
Results:
Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953).
Conclusion
Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.
3.Impact of HER2-Low Status on Pathologic Complete Response and Survival Outcome Among Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy
Young Joo LEE ; Tae-Kyung YOO ; Sae Byul LEE ; Il Yong CHUNG ; Hee Jeong KIM ; Beom Seok KO ; Jong Won LEE ; Byung Ho SON ; Sei Hyun AHN ; Hyehyun JEONG ; Jae Ho JUNG ; Jin-Hee AHN ; Kyung Hae JUNG ; Sung-Bae KIM ; Hee Jin LEE ; Gyungyub GONG ; Jisun KIM
Journal of Breast Cancer 2025;28(1):11-22
Purpose:
This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment.
Methods:
This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed.
Results:
Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953).
Conclusion
Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.
4.2023 Korean sexually transmitted infections treatment guidelines for Mycoplasma genitalium by KAUTII
Seung-Ju LEE ; Jin Bong CHOI ; Sangrak BAE ; Seong Woong NA ; Hae Do JUNG ; Hyun Jin JUNG ; Seung Il JUNG ; Phil Hyun SONG ; Gilho LEE
Investigative and Clinical Urology 2024;65(1):16-22
The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency updated the Korean sexually transmitted infections (STIs) guidelines to respond to the changing epidemiologic trends, evolving scientific evidence, and advances in laboratory diagnostics and research. The main recommendations in the Mycoplasma genitalium infection parts of the Korean STIs guidelines 2023 revision are as follows: 1) For initial treatment: azithromycin 500 mg orally in a single dose, then 250 mg once daily for 4 days. 2) In case of treatment failure or recurrence, a macrolide susceptibility/resistance test is required, when susceptibility/resistance test is not feasible, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g orally on the first day, then azithromycin 500 mg orally once daily for 3 days and then a test-of-cure should be considered 3 weeks after completion of therapy. 3) In case of macrolide sensitivity, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g orally initial dose, then azithromycin 500 mg orally once daily for 3 days. 4) In case of macrolide resistance, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by moxifloxacin 400 mg orally once daily for 7 days. In the Korean STIs guideline 2023, macrolide resistance-guided antimicrobial therapy was emphasized due to the increased prevalence of macrolide resistance worldwide. Therefore, in case of treatment failure or recurrence, a macrolide susceptibility/resistance test is required.
5.Impact of longitudinal tumor location on postoperative outcomes in gallbladder cancer: Fundus and body vs. neck and cystic duct, a retrospective multicenter study
Kil Hwan KIM ; Ju Ik MOON ; Jae Woo PARK ; Yunghun YOU ; Hae Il JUNG ; Hanlim CHOI ; Si Eun HWANG ; Sungho JO
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(4):474-482
Background:
s/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC.
Methods:
A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon–Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location.
Results:
Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location.
Conclusions
NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.
6.Impact of longitudinal tumor location on postoperative outcomes in gallbladder cancer: Fundus and body vs. neck and cystic duct, a retrospective multicenter study
Kil Hwan KIM ; Ju Ik MOON ; Jae Woo PARK ; Yunghun YOU ; Hae Il JUNG ; Hanlim CHOI ; Si Eun HWANG ; Sungho JO
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(4):474-482
Background:
s/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC.
Methods:
A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon–Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location.
Results:
Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location.
Conclusions
NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.
7.Impact of longitudinal tumor location on postoperative outcomes in gallbladder cancer: Fundus and body vs. neck and cystic duct, a retrospective multicenter study
Kil Hwan KIM ; Ju Ik MOON ; Jae Woo PARK ; Yunghun YOU ; Hae Il JUNG ; Hanlim CHOI ; Si Eun HWANG ; Sungho JO
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(4):474-482
Background:
s/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC.
Methods:
A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon–Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location.
Results:
Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location.
Conclusions
NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.
8.Practice guidelines for managing extrahepatic biliary tract cancers
Hyung Sun KIM ; Mee Joo KANG ; Jingu KANG ; Kyubo KIM ; Bohyun KIM ; Seong-Hun KIM ; Soo Jin KIM ; Yong-Il KIM ; Joo Young KIM ; Jin Sil KIM ; Haeryoung KIM ; Hyo Jung KIM ; Ji Hae NAHM ; Won Suk PARK ; Eunkyu PARK ; Joo Kyung PARK ; Jin Myung PARK ; Byeong Jun SONG ; Yong Chan SHIN ; Keun Soo AHN ; Sang Myung WOO ; Jeong Il YU ; Changhoon YOO ; Kyoungbun LEE ; Dong Ho LEE ; Myung Ah LEE ; Seung Eun LEE ; Ik Jae LEE ; Huisong LEE ; Jung Ho IM ; Kee-Taek JANG ; Hye Young JANG ; Sun-Young JUN ; Hong Jae CHON ; Min Kyu JUNG ; Yong Eun CHUNG ; Jae Uk CHONG ; Eunae CHO ; Eui Kyu CHIE ; Sae Byeol CHOI ; Seo-Yeon CHOI ; Seong Ji CHOI ; Joon Young CHOI ; Hye-Jeong CHOI ; Seung-Mo HONG ; Ji Hyung HONG ; Tae Ho HONG ; Shin Hye HWANG ; In Gyu HWANG ; Joon Seong PARK
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):161-202
Background:
s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021.
Methods:
Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop.
Results:
In November 2021, the finalized draft was presented for public scrutiny during a formal hearing.
Conclusions
The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.
9.The Anti-Diabetic Pinitol Improves Damaged Fibroblasts
Ji-Yong JUNG ; Joong Hyun SHIM ; Su Hae CHO ; Il-Hong BAE ; Seung Ha YANG ; Jinsick KIM ; Hye Won LIM ; Dong Wook SHIN
Biomolecules & Therapeutics 2024;32(2):224-230
Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known.Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVAinduced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.
10.Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814)
Younghee PARK ; Tae Hyun KIM ; Kyubo KIM ; Jeong Il YU ; Wonguen JUNG ; Jinsil SEONG ; Woo Chul KIM ; Jin Hwa CHOI ; Ah Ram CHANG ; Bae Kwon JEONG ; Byoung Hyuck KIM ; Tae Gyu KIM ; Jin Hee KIM ; Hae Jin PARK ; Hyun Soo SHIN ; Jung Ho IM ; Eui Kyu CHIE
Cancer Research and Treatment 2024;56(1):272-279
Purpose:
Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.
Materials and Methods:
Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.
Results:
After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.
Conclusion
Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

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