Cancer Research and Treatment

Original Articles

Ten-Year Follow-Up Clinical Outcomes and the Role of Adjuvant Chemotherapy in HER2-Positive Patients with Microinvasive Breast Cancer: Yeokyeong Shin, Soo-Young Lee, Hyehyun Jeong, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, BeomSeok Ko, Ji Sun Kim, Il Yong Chung, Hee Jin Lee, Gyungyub Gong, Sae Byul Lee, Jae Ho Jeong; Received November 22, 2024 Accepted March 3, 2025 Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1120 [Accepted]

Abstract PDF: Purpose
Although HER2 positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy.
Materials and Methods
The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed.
Results
The analysis included 799 female patients. The median age was 51 years (range, 23–79), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n = 238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% CI, 114.0–127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1–93.3), 97.5% (95% CI, 96.4–98.7), and 98.8% (95% CI, 98.0–99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease.
Conclusion
A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

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Breast cancer

A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols: Min Chong Kim, Eun Yoon Cho, So Yeon Park, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Ho-chang Lee, Jin Ye Yoo, Hee Sung Kim, Bomi Kim, Wan Seop Kim, Nari Shin, Young Hee Maeng, Hun Soo Kim, Sun Young Kwon, Chungyeul Kim, Sun-Young Jun, Gui Young Kwon, Hye Jeong Choi, So Mang Lee, Ji Eun Choi, Ae Ri An, Hyun Joo Choi, EunKyung Kim, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; Cancer Res Treat. 2024;56(4):1096-1104. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2024.092

Abstract PDF Supplementary Material PubReader ePub

Purpose
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
Virchows Archiv.2024; 485(6): 1117. CrossRef
Breast Cancer: Extracellular Matrix and Microbiome Interactions
Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Julio Plaza-Diaz
International Journal of Molecular Sciences.2024; 25(13): 7226. CrossRef

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Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer: Young-Gon Kim, In Hye Song, Seung Yeon Cho, Sungchul Kim, Milim Kim, Soomin Ahn, Hyunna Lee, Dong Hyun Yang, Namkug Kim, Sungwan Kim, Taewoo Kim, Daeyoung Kim, Jonghyeon Choi, Ki-Sun Lee, Minuk Ma, Minki Jo, So Yeon Park, Gyungyub Gong; Cancer Res Treat. 2023;55(2):513-522. Published online September 6, 2022; DOI: https://doi.org/10.4143/crt.2022.055

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Purpose
Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin–stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients.
Materials and Methods
A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study.
Results
The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis.
Conclusion
In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

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Detection of metastatic breast carcinoma in sentinel lymph node frozen sections using an artificial intelligence-assisted system
Chia-Ping Chang, Chih-Yi Hsu, Hsiang Sheng Wang, Peng-Chuna Feng, Wen-Yih Liang
Pathology - Research and Practice.2025; 267: 155836. CrossRef
Value of frozen section to tailor surgical staging in apparent early-stage epithelial ovarian cancer
Stefano Di Berardino, Nicolò Bizzarri, Marianna Ciancia, Francesca Moro, Belen Padial Urtueta, Claudia Marchetti, Gian Franco Zannoni, Giovanni Scambia, Anna Fagotti
International Journal of Gynecological Cancer.2025; : 101746. CrossRef
Comparing the diagnostic efficacy of optical coherence tomography and frozen section for margin assessment in breast-conserving surgery: a meta-analysis
Shishun Fan, Huirui Zhang, Zhenyu Meng, Ang Li, Yuqing Luo, Yueping Liu
Journal of Clinical Pathology.2024; 77(8): 517. CrossRef
Intraoperative Margin Assessment in Breast Conservation Surgery: A Necessity or a Luxury?
Srijan Shukla, Nisha Hariharan
Annals of Surgical Oncology.2023; 30(9): 5314. CrossRef

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The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer: In Hye Song, Young-Ae Kim, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, Yeon ho Choi, Heejae Lee, Jeong-Han Seo, Youngjin Cho, Sung Wook Jung, Hee Jeong Kim, Sei Hyun Ahn, Hee Jin Lee, Gyungyub Gong; Cancer Res Treat. 2022;54(4):1111-1120. Published online December 21, 2021; DOI: https://doi.org/10.4143/crt.2021.1017

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Purpose
The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.
Materials and Methods
The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection.
Results
HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group.
Conclusion
MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

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Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer: Chromosomal Bioinformatics Analysis
Bernard Friedenson
JMIRx Med.2025; 6: e50712. CrossRef
Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer
Julio C Tinoco, Harmony I Saunders, Lauryn Rose Werner, Xiaopeng Sun, Eilidh I Chowanec, Amanda Heard, Prabhakar Chalise, Jeffery M Vahrenkamp, Andrea E Wilson, Cong-Xiao Liu, Gangjun Lei, Junping Wei, Hugo Cros, Hisham Mohammed, Melissa Troester, Charles
Journal for ImmunoTherapy of Cancer.2025; 13(3): e010179. CrossRef
Estrogen receptor regulation of the immune microenvironment in breast cancer
Conor McGuinness, Kara L. Britt
The Journal of Steroid Biochemistry and Molecular Biology.2024; 240: 106517. CrossRef
Bioinformatic-Experimental Screening Uncovers Multiple Targets for Increase of MHC-I Expression through Activating the Interferon Response in Breast Cancer
Xin Li, Zilun Ruan, Shuzhen Yang, Qing Yang, Jinpeng Li, Mingming Hu
International Journal of Molecular Sciences.2024; 25(19): 10546. CrossRef
Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity
Alexandra Moisand, Mathilde Madéry, Thomas Boyer, Charlotte Domblides, Céline Blaye, Nicolas Larmonier
International Journal of Molecular Sciences.2023; 24(20): 15048. CrossRef

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Challenge for Diagnostic Assessment of Deep Learning Algorithm for Metastases Classification in Sentinel Lymph Nodes on Frozen Tissue Section Digital Slides in Women with Breast Cancer: Young-Gon Kim, In Hye Song, Hyunna Lee, Sungchul Kim, Dong Hyun Yang, Namkug Kim, Dongho Shin, Yeonsoo Yoo, Kyowoon Lee, Dahye Kim, Hwejin Jung, Hyunbin Cho, Hyungyu Lee, Taeu Kim, Jong Hyun Choi, Changwon Seo, Seong il Han, Young Je Lee, Young Seo Lee, Hyung-Ryun Yoo, Yongju Lee, Jeong Hwan Park, Sohee Oh, Gyungyub Gong; Cancer Res Treat. 2020;52(4):1103-1111. Published online June 30, 2020; DOI: https://doi.org/10.4143/crt.2020.337

Abstract PDF PubReader ePub

Purpose
Assessing the status of metastasis in sentinel lymph nodes (SLNs) by pathologists is an essential task for the accurate staging of breast cancer. However, histopathological evaluation of sentinel lymph nodes by a pathologist is not easy and is a tedious and time-consuming task. The purpose of this study is to review a challenge competition (HeLP 2018) to develop automated solutions for the classification of metastases in hematoxylin and eosin–stained frozen tissue sections of SLNs in breast cancer patients.
Materials and Methods
A total of 297 digital slides were obtained from frozen SLN sections, which include post–neoadjuvant cases (n = 144, 48.5%) in Asan Medical Center, South Korea. The slides were divided into training, development, and validation sets. All of the imaging datasets have been manually segmented by expert pathologists. A total of 10 participants were allowed to use the Kakao challenge platform for six weeks with two P40 GPUs. The algorithms were assessed in terms of the AUC (area under receiver operating characteristic curve).
Results
The top three teams showed 0.986, 0.985, and 0.945 AUCs for the development set and 0.805, 0.776, and 0.765 AUCs for the validation set. Micrometastatic tumors, neoadjuvant systemic therapy, invasive lobular carcinoma, and histologic grade 3 were associated with lower diagnostic accuracy.
Conclusion
In a challenge competition, accurate deep learning algorithms have been developed, which can be helpful in making frozen diagnosis of intraoperative sentinel lymph node biopsy. Whether this approach has clinical utility will require evaluation in a clinical setting

Citations

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Detection of metastatic breast carcinoma in sentinel lymph node frozen sections using an artificial intelligence-assisted system
Chia-Ping Chang, Chih-Yi Hsu, Hsiang Sheng Wang, Peng-Chuna Feng, Wen-Yih Liang
Pathology - Research and Practice.2025; 267: 155836. CrossRef
Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer
Young-Gon Kim, In Hye Song, Seung Yeon Cho, Sungchul Kim, Milim Kim, Soomin Ahn, Hyunna Lee, Dong Hyun Yang, Namkug Kim, Sungwan Kim, Taewoo Kim, Daeyoung Kim, Jonghyeon Choi, Ki-Sun Lee, Minuk Ma, Minki Jo, So Yeon Park, Gyungyub Gong
Cancer Research and Treatment.2023; 55(2): 513. CrossRef
Artificial intelligence and frozen section histopathology: A systematic review
Benjamin G. Gorman, Mark A. Lifson, Nahid Y. Vidal
Journal of Cutaneous Pathology.2023; 50(9): 852. CrossRef
Effectiveness of transfer learning for enhancing tumor classification with a convolutional neural network on frozen sections
Young-Gon Kim, Sungchul Kim, Cristina Eunbee Cho, In Hye Song, Hee Jin Lee, Soomin Ahn, So Yeon Park, Gyungyub Gong, Namkug Kim
Scientific Reports.2020;[Epub] CrossRef

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BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy: Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro; Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019; DOI: https://doi.org/10.4143/crt.2018.598

Abstract PDF PubReader ePub

Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

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PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis
Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
Breast Cancer Research and Treatment.2023; 201(2): 161. CrossRef
Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
Translational Oncology.2023; 37: 101738. CrossRef
Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations
Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
JCO Precision Oncology.2022;[Epub] CrossRef
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
Ugo Testa, Germana Castelli, Elvira Pelosi
Medical Sciences.2020; 8(1): 18. CrossRef

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Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers: Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee; Cancer Res Treat. 2019;51(1):80-89. Published online February 26, 2018; DOI: https://doi.org/10.4143/crt.2017.500

Abstract PDF PubReader ePub

Purpose
In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear.
Materials and Methods
We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts.
Results
In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041).
Conclusion
Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.

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Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens
Aleksandra Wroblewska, Maxime Dhainaut, Benjamin Ben-Zvi, Samuel A. Rose, Eun Sook Park, El-Ad David Amir, Anela Bektesevic, Alessia Baccarini, Miriam Merad, Adeeb H. Rahman, Brian D. Brown
Cell.2018; 175(4): 1141. CrossRef

9,708 View
317 Download
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29 Crossref

No Association of Positive Superficial and/or Deep Margins with Local Recurrence in Invasive Breast Cancer Treated with Breast-Conserving Surgery: Tae In Yoon, Jong Won Lee, Sae Byul Lee, Guiyun Sohn, Jisun Kim, Il Young Chung, Hee Jeong Kim, Beom Seok Ko, Byung Ho Son, Gyungyub Gong, Sung-Bae Kim, Su Ssan Kim, Seung Do Ahn, Minsung Chung, Sei Hyun Ahn; Cancer Res Treat. 2018;50(1):275-282. Published online April 14, 2017; DOI: https://doi.org/10.4143/crt.2017.041

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy.
Materials and Methods
In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed.
Results
Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57).
Conclusion
Superficial and/or deep margin involvement following BCS is not an important predictor for LR.

Citations

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Locoregional Recurrence-Free Survival in Postmastectomy Breast Cancer: A Comparative Longitudinal Study of Hypofractionated Versus Conventional Fractionated Radiation Therapy
Suma Susan Meloot, Ciniraj Raveendran, IP Yadev
Indian Journal of Surgical Oncology.2025;[Epub] CrossRef
Assessment of Eligibility and Utilization of Accelerated Partial Breast Irradiation in Korean Breast Cancer Patients (KROG 22-15)
Seok-Joo Chun, Ji Hwan Jo, Yong Bae Kim, Sangjoon Park, Sung-Ja Ahn, Su Ssan Kim, Kyubo Kim, Kyung Hwan Shin
Cancer Research and Treatment.2024; 56(2): 549. CrossRef
Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy
Jong-Ho Cheun, Young Joo Lee, Jun-Hee Lee, Yungil Shin, Jung Whan Chun, Soo Yeon Baek, Hong-Kyu Kim, Han-Byoel Lee, Jonghan Yu, Byung Joo Chae, Wonshik Han, Jeong Eon Lee
Breast Cancer Research and Treatment.2022; 194(3): 683. CrossRef
Comparison of Recurrence Rate Between Re-Excision With Radiotherapy and Radiotherapy-Only Groups in Surgical Margin Involvement of In Situ Carcinoma
Jun-Hee Lee, Hyunjun Lee, Yoon Ju Bang, Jai Min Ryu, Se Kyung Lee, Jonghan Yu, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Byung Joo Chae
Journal of Breast Cancer.2022; 25(4): 288. CrossRef
Updates and Debate Concerning Margin Adequacy and Management following Breast-Conserving Surgery
Serena Bertozzi, Ambrogio P Londero, Jose Andres Diaz Nanez, Francesco Leone, Barbara Baita, Lucia La Verghetta, Milena Nobile, Daria Almesberger, Carla Cedolini
Clinical and Experimental Obstetrics & Gynecology.2022;[Epub] CrossRef
Feasibility and safety of breast-conserving surgery via a periareolar incision for cancers located far from the nipple–areolar complex: a retrospective study
Joohyun Woo, Jihae Lee, Se Hyun Paek, Woosung Lim
Journal of Cancer Research and Clinical Oncology.2021; 147(3): 893. CrossRef
Breast-conserving surgery with 3D-printed surgical guide: a single-center, prospective clinical study
Zhen-Yu Wu, Hee Jeong Kim, Jongwon Lee, Il Yong Chung, Jisun Kim, Saebyeol Lee, Byung Ho Son, Sei-Hyun Ahn, Hak Hee Kim, Joon Beom Seo, Jae Ho Jeong, Gyungyub Gong, Namkug Kim, BeomSeok Ko
Scientific Reports.2021;[Epub] CrossRef
Usefulness of 3D-surgical guides in breast conserving surgery after neoadjuvant treatment
Han Shin Lee, Hee Jeong Kim, Il Yong Chung, Jisun Kim, Sae Byul Lee, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Hak Hee Kim, Joon Beom Seo, Jin Hee Ahn, Gyungyub Gong, Sangwook Lee, Namkug Kim, Beom Seok Ko
Scientific Reports.2021;[Epub] CrossRef
Partial chest wall radiation therapy for positive or close surgical margins after modified radical mastectomy for breast cancer without lymph node metastasis
Naoya Ishibashi, Haruna Nishimaki, Toshiya Maebayashi, Keita Adachi, Kenichi Sakurai, Shinobu Masuda, Masaharu Hata, Masahiro Okada
Asia-Pacific Journal of Clinical Oncology.2020; 16(1): 28. CrossRef
Impact of Oncotype DX Recurrence Score on the Patterns of Locoregional Recurrence in Breast Cancer (Korean Radiation Oncology Group 19-06)
Kyubo Kim, Jinhong Jung, Kyung Hwan Shin, Jin Ho Kim, Ji Hyun Chang, Su Ssan Kim, Haeyoung Kim, Won Park, Yong Bae Kim, Jee Suk Chang
Journal of Breast Cancer.2020; 23(3): 314. CrossRef
Magnetic resonance imaging based 3-dimensional printed breast surgical guide for breast-conserving surgery in ductal carcinoma in situ: a clinical trial
Zhen-Yu Wu, Aisha Alzuhair, Heejeong Kim, Jong Won Lee, Il Yong Chung, Jisun Kim, Sae Byul Lee, Byung Ho Son, Gyungyub Gong, Hak Hee Kim, Joon Beom Seo, Sei Hyun Ahn, Namkug Kim, BeomSeok Ko
Scientific Reports.2020;[Epub] CrossRef
Aktuelle chirurgische Therapie des Mammakarzinoms
Jasmin Zeindler, Fabienne Schwab
InFo Hämatologie + Onkologie.2019; 22(4): 15. CrossRef
Comparing long-term local recurrence rates of surgical and non-surgical management of close anterior margins in breast conserving surgery
George Boundouki, Joseph Ryan Wong Sik Hee, Natalie Croghan, Katie Stocking, Andrew Pieri, Adam Critchley, Cliona C. Kirwan, James R. Harvey
Breast Cancer Research and Treatment.2019; 176(2): 311. CrossRef
Therapy of isolated locoregional recurrent carcinoma of the breast
Lena Gabriel, Marina Schmidt, Stephanie Juhasz-Böss, Patrick Melchior, Anika von Heesen, Gilda Schmidt, Nicole Kranzhöfer, Erich-Franz Solomayer, Ingolf Juhasz-Böss, Georg-Peter Breitbach
Archives of Gynecology and Obstetrics.2019; 300(2): 365. CrossRef

12,418 View
431 Download
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Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer: In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee; Cancer Res Treat. 2017;49(2):399-407. Published online July 27, 2016; DOI: https://doi.org/10.4143/crt.2016.215

Abstract PDF Supplementary Material PubReader ePub

Purpose
The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined.
Materials and Methods
A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13 mRNA expression levels using a NanoString assay (NanoString Technologies).
Results
The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate.
Conclusion
MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.

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Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers: So Jeong Lee, Cheong-Soo Hwang, Young-Keum Kim, Hyun Jung Lee, Sang-Jeong Ahn, Nari Shin, Jung Hee Lee, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Chang Hun Lee, Gi Young Huh, Mi Young Sol, Hee Jin Lee, Gyungyub Gong, Jee Yeon Kim, Ahrong Kim; Cancer Res Treat. 2017;49(2):313-321. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.098

Abstract PDF PubReader ePub

Purpose
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers.
Materials and Methods
Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray.
Results
MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor.
Conclusion
High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

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Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors
Mart van Rijthoven, Simon Obahor, Fabio Pagliarulo, Maries van den Broek, Peter Schraml, Holger Moch, Jeroen van der Laak, Francesco Ciompi, Karina Silina
Communications Medicine.2024;[Epub] CrossRef
The roles of tertiary lymphoid structures in chronic diseases
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Nature Reviews Nephrology.2023; 19(8): 525. CrossRef
NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
Jing Zhang, Mingyue Fan, Chanjuan Jin, Zhaoying Wang, Yutong Yao, Yueru Shi, Xin Hu, Youzhong Wan
Archives of Biochemistry and Biophysics.2022; 727: 109346. CrossRef
Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination
Yi Wang, Chunzhao Li, Xiaohan Chi, Xijian Huang, Hua Gao, Nan Ji, Yang Zhang
Frontiers in Oncology.2022;[Epub] CrossRef
Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
Abrar I. Aljohani, Chitra Joseph, Sasagu Kurozumi, Omar J. Mohammed, Islam M. Miligy, Andrew R. Green, Emad A. Rakha
Breast Cancer Research and Treatment.2020; 181(3): 541. CrossRef
Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Cancer Research and Treatment.2019; 51(1): 80. CrossRef
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Jiawei Chen, Chongxian Hou, Peng Wang, Yong Yang, Dong Zhou
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Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Scientific Reports.2017;[Epub] CrossRef

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Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients: Min Kyoung Kim, Sung-Bae Kim, Jin Hee Ahn, Soon Im Lee, Sei-Hyun Ahn, Byung Ho Son, Gyungyub Gong, Hak-Hee Kim, Jung-Shin Lee, Yoon-Koo Kang, Woo Kun Kim; Cancer Res Treat. 2006;38(4):206-213. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.206

Abstract PDF PubReader ePub

Purpose

To evaluate the efficacy of gemcitabine-based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2^nd-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and gemcitabine/capecitabine (GX).

Materials and Methods

Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively.

Results

The median number of prior metastatic chemotherapy regimens was 2 (range 0~4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5~9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0~4.2 months). Compared with monotherapy (G), com - bination therapy with vinorelbine or capecitabine (GV/GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival.

Conclusions

The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2^nd-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

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A Systematic Review of Vinorelbine for the Treatment of Breast Cancer
Ying-Chun Xu, Hong-Xia Wang, Lei Tang, Yue Ma, Feng-Chun Zhang
The Breast Journal.2013; 19(2): 180. CrossRef

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Growth Suppression and Induction of Chemosensitivity in Human Gallbladder Epithelial Carcinoma Cells (GBCE) by Adenovirus-Mediated Transfer of the Wild-type p53 Gene: Sung Bae Kim, Myung Hwan Kim, Sung Koo Lee, Tae Won Kim, Cheolwon Suh, Jeong Sik Shin, Jung Sun Park, Eun Soon Kim, Gyungyub Gong, Jung Shin Lee, Woo Kun Kim, Sang Hee Kim; Cancer Res Treat. 2003;35(6):521-527. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.521

Abstract PDF: PURPOSE
Mutations in the p53 gene are reported in 50~90% of gallbladder and bile duct cancer, and have been implicated in chemoresistance. We undertook this study to determine whether the introduction of the wild type p53 gene into GBCE (human gallbladder cancer cell line with a heterozygous p53 mutation) by an adenoviral vector could increase the sensitivity of the cell to 5-FU, a commonly used drug in the treatment of gallbladder cancer. MATERIALS AND METHODS: GBCE cells were transfected with either Ad/p53 or Ad/E1 in the presence of 5-FU. Gene expression was confirmed by western blotting. Nude mice were injected subcutaneously with GBCE cells. When tumors formed, intratumoral injection of Ad/p53 was performed. Reduction of tumor size was compared in two weeks of Ad/p53 gene transfection. RESULTS: Ad/53 transfection induced a dose-dependent inhibition of tumor growth. Tumor colony formation was more inhibited with p53 gene transfection than with mock transfection in the presence of 5-FU. The reduction in tumor size was more pronounced with p53 transfection than with mock infection.
CONCLUSION
These treatment modalities could be utilized in the treatment of p53 mutant human gallbladder cancers.

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