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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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;[Epub]     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
  • 1,876 View
  • 158 Download
  • 2 Crossref
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Next-Generation Sequencing in Breast Cancer Patients: Real-World Data for Precision Medicine
Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho
Cancer Res Treat. 2024;56(1):149-161.   Published online August 11, 2023
DOI: https://doi.org/10.4143/crt.2023.800
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer.
Materials and Methods
We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500.
Results
The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation.
Conclusion
NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

Citations

Citations to this article as recorded by  
  • Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
    Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
    Pathology.2024; 56(5): 653.     CrossRef
  • Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer
    Elena Guerini-Rocco, Konstantinos Venetis, Giulia Cursano, Eltjona Mane, Chiara Frascarelli, Francesco Pepe, Mariachiara Negrelli, Edoardo Olmeda, Davide Vacirca, Alberto Ranghiero, Dario Trapani, Carmen Criscitiello, Giuseppe Curigliano, Christian Rolfo,
    Critical Reviews in Oncology/Hematology.2024; 201: 104427.     CrossRef
  • An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer
    Yi Bi, Xiao Lv, Ke Wang, Jinyu Wu, Xiang Shi, Xiaodong Zheng, Xiaogang Lin
    Frontiers in Bioengineering and Biotechnology.2024;[Epub]     CrossRef
  • NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
    Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
    Romanian Journal of Morphology and Embryology.2024; 65(2): 195.     CrossRef
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  • 4 Web of Science
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Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer
Ji-Yeon Kim, Kyunghee Park, Hae Hyun Jung, Eunjin Lee, Eun Yoon Cho, Kwang Hee Lee, Soo Youn Bae, Se Kyung Lee, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Cancer Res Treat. 2016;48(4):1338-1350.   Published online February 18, 2016
DOI: https://doi.org/10.4143/crt.2015.430
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).
Materials and Methods
We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients.
Results
Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57,respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patientswith a TP53 missense mutation (5-year distantrecurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316).
Conclusion
Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients.

Citations

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Implications of Bone-Only Metastases in Breast Cancer: Favorable Preference with Excellent Outcomes of Hormone Receptor Positive Breast Cancer
Su Jin Lee, Silvia Park, Hee Kyung Ahn, Jun Ho Yi, Eun Yoon Cho, Jong Mu Sun, Jeong Eon Lee, Seok Jin Nam, Jung-Hyun Yang, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im
Cancer Res Treat. 2011;43(2):89-95.   Published online June 30, 2011
DOI: https://doi.org/10.4143/crt.2011.43.2.89
AbstractAbstract PDFPubReaderePub
PURPOSE
The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis.
MATERIALS AND METHODS
Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases.
RESULTS
The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077).
CONCLUSION
Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'

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Expression of Cyclooxygenase-2 and Tumor Microvessel Density in Colorectal Cancer
Seoung Wan Chae, Jin Hee Sohn, Eo Jin Kim, Eun Yoon Cho, Bong Hwa Lee
Cancer Res Treat. 2003;35(5):400-406.   Published online October 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.5.400
AbstractAbstract PDF
PURPOSE
The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of human cancer. This study investigated the COX-2 expression in colorectal cancer, and its relationships with tumor angiogenesis and the clinicopathological factors. MATERIALS AND METHODS: The expression of the COX-2 protein and microvessel density were evaluated, using immunohistochemical methods, in 21 normal colonic mucosa and 190 human colorectal carcinomas. Correlations between COX-2 expression and microvessel density, as well as various clinicopathological factors, were studied in colorectal carcinomas. RESULTS: The COX-2 protein expression in epithelial cells was increased in 169 of the 190 adenocarcinoma cases (88.9%), but in only 1 of the 21 (4.8%) normal mucosa cases. The COX-2 expression was significantly increased in the differentiated compared with the undifferentiated colorectal carcinomas (p<0.05), and significantly correlated with the depth of invasion and microvessel density (p<0.05). Rectal cancers had more COX-2 positive cases than the colon cancers (p<0.05). However, there were no significant differences in the tumor size and the presence of lymphatic or vascular invasion. CONCLUSION: The overexpression of cyclooxygenase-2 in colorectal carcinomas seems to play a role in the invasion and angiogenesis of the tumors, so may be a useful marker of the prognosis. The prominent expression was also demonstrated in differentiated colorectal cancers.

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  • Expression of Cyclooxygenase (COX)-2 as a Prognostic Factor in Nasopharyngeal Cancer
    Kyubo Kim, Hong-Gyun Wu, Suk Won Park, Chong Jai Kim, Charn Il Park
    Cancer Research and Treatment.2004; 36(3): 187.     CrossRef
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Subtypes of Epstein - Barr Virus in Malignant Lymphoma in Korea
Kyung Eun Choi, Eun Yoon Cho, Chan Kum Park, Won Keun Lee, Young Hyeh Ko
J Korean Cancer Assoc. 1998;30(2):338-349.
AbstractAbstract PDF
PURPOSE
Epstein-Barr virus(EBV) exists in the human population in two genetic forms, usually referred to as type 1 and type 2 which have been defined on the basis of sequence divergence in the EBNA-2 and EBNA-3 family genes. In this study, we were intended to investigate whether the subtypes of EBV in malignant lymphoma in Korea were associated with specific disease entities and geographical distribution.
MATERIALS AND METHODS
Biopsy samples obtained from 18 Korean patients with malignant lymphoma including Hodgkin's disease(3 cases), B cell lymphoma(1 case), and NK/T cell lymphoma(14 cases) were analyzed to determine the subtype of EBV infected therein. DNA was extracted from formalin-fixed, paraffin-embeded tissues by ordinary method and specific viral sequences were sought using the polymerase chain reaction(PCR) and Southern blot hybridization assay. Oligonucleotide primers used for examination of EBV strain type were derived from the EBNA-3B and EBNA-3C coding regions. As a control, four cases of reactive hyperplasia were analyzed.
RESULTS
The two of four reactive hyperplasia cases were associated with type 1 and the rest of two cases with both types. Among the 18 cases with malignant lymphoma, thirteen cases(72%) had type 1, one(6%) had type 2, and four(22%) had dual infections with both types. In case of NK/T cell lymphoma(14 cases) occupying 78% of 18 biopsy samples, 86%(12 cases) were associated with type 1, 7%(1 case) with type 2, and 7%(1 case) with both types. In case of Hodgkin's disease, all of three cases had both types. B cell lymphoma taking only one case of twenty two cases was determined as type 1.
CONCLUSION
These observations indicated that type 1 EBV was predominant in Korean patients with malignant lymphoma, especially NK/T cell lymphoma and showed high frequency of dual viral infections(22%) in Hodgkin's disease as well as in reactive hyperplasia.
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