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8. Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA

Author

Bae, Mingyun, Kim, Gyuhee, Lee, Tae-Rim, Ahn, Jin Mo, Park, Hyunwook, Park, Sook Ryun, Song, Ki Byung, Jun, Eunsung, Oh, Dongryul, Lee, Jeong-Won, Park, Young Sik, Song, Ki-Won, Byeon, Jeong-Sik, Kim, Bo Hyun, Sohn, Joo Hyuk, Kim, Min Hwan, Kim, Gun Min, Chie, Eui Kyu, Kang, Hyun-Cheol, Kong, Sun-Young, Woo, Sang Myung, Lee, Jeong Eon, Ryu, Jai Min, Lee, Junnam, Kim, Dasom, Ki, Chang-Seok, Cho, Eun-Hae, and Choi, Jung Kyoon

Published
2023
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20. Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel.

Author

Park, Chanyong, Lim, Wanyoung, Song, Ryungeun, Han, Jeonghun, You, Daeun, Kim, Sangmin, Lee, Jeong Eon, van Noort, Danny, Mandenius, Carl-Fredrik, Lee, Jinkee, Hyun, Kyung-A., Jung, Hyo-Il, and Park, Sungsu

Subjects
CANCER cells, TRIPLE-negative breast cancer, DRAG force, CELL populations, MICROFLUIDIC devices, SUPERCONDUCTING coils
Abstract

Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSμC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSμC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 μm) toward the inner wall, while directing smaller ones (avg. diameter: 23 μm) outward. Utilizing ITSμC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSμC suggests its potential in differentiating a wide range of heterogeneous cell populations. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

Author

Azim Jr, Hatem A., Niman, Samuel M., Partridge, Ann H., Demeestere, Isabelle, Ruggeri, Monica, Colleoni, Marco, Saura, Cristina, Shimizu, Chikako, Saetersdal, Anna B., Kroep, Judith R., Mailliez, Audrey, Warner, Ellen, Borges, Virginia F., Amant, Frédéric, Gombos, Andrea, Kataoka, Akemi, Rousset-Jablonski, Christine, Borstnar, Simona, Takei, Junko, and Lee, Jeong Eon

Published
2024
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22. Measuring patient‐reported distress from breast magnetic resonance imaging: Development and validation of the MRI‐related distress scale (MRI‐DS).

Author

Kang, Danbee, Kim, Sooyeon, Han, Jiyoon, Kim, Youngha, Cho, Juhee, Lee, Jeong Eon, and Ko, Eun Sook

Subjects
MAGNETIC resonance mammography, MEDICAL personnel as patients, MAGNETIC resonance imaging, BREAST exams, PSYCHOLOGICAL distress
Abstract

Objective: Although breast magnetic resonance imaging (MRI) is a valuable screening tool, breast MRI testing burden was associated with cancer worry and quality of life. We aimed to develop and validate the MRI‐related distress scale (MRI‐DS) to assess comprehensive distress specifically related to breast MRI. Methods: We enrolled women aged above 18 years, diagnosed breast cancer, had MRI examination at least one time, and who could speak and read Korean in phase I and enrolled women aged above 18 years, visited outpatient clinic of breast general surgery, had undergone MRI examination at least once, and could speak and read Korean in phase II. We excluded patients who had any physical or psychiatric conditions in both phases. We recruited from a tertiary university‐based hospital in South Korea between April and August 2023. Results: All 18 items had acceptable levels of item correlation (≥0.30) in the explanatory factor analysis with a four‐factor solution. The fit indices for the four‐factor solution model were good. The discriminant validity of the MRI‐DS had a moderate correlation with general anxiety or quality of life. In the known‐group analysis, those who reported MRI as the most burden breast examination had higher total scores. Conclusion: The validity of the MRI‐DS has been confirmed as a scale for measuring the specific distress caused by breast MRI. The MRI‐DS is recommended to health professional to communicate with patients with MRI. Clinical Implications: It can be used to assess the distress associated with MRI screening in breast cancer patients. Physician could use MRI‐DS to discuss the reasons for distress caused by breast MRI screening and to address specific sources of discomfort associated with it. [ABSTRACT FROM AUTHOR]

Published
2024
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31. The Prognostic Impact of HER2-Low and Menopausal Status in Triple-Negative Breast Cancer.

Author

Park, Woong Ki, Nam, Seok Jin, Kim, Seok Won, Lee, Jeong Eon, Yu, Jonghan, Lee, Se Kyung, Ryu, Jai Min, and Chae, Byung Joo

Subjects
BREAST cancer prognosis, RESEARCH funding, BREAST tumors, MENOPAUSE, FISHER exact test, RETROSPECTIVE studies, MULTIVARIATE analysis, CHI-squared test, MANN Whitney U Test, DESCRIPTIVE statistics, ADJUVANT chemotherapy, KAPLAN-Meier estimator, ONCOGENES, COMBINED modality therapy, MEDICAL records, ACQUISITION of data, PROGRESSION-free survival, SURVIVAL analysis (Biometry), DATA analysis software, CONFIDENCE intervals, OVERALL survival, REGRESSION analysis, PROPORTIONAL hazards models
Abstract

Simple Summary: Triple-negative breast cancer (TNBC) is a challenging form of breast cancer known for its aggressive nature and limited treatment options. The DESTINY-Breast 04 trial has demonstrated improved survival outcomes in metastatic human epithelial growth factor receptor 2 (HER2)-low breast cancer patients treated with trastuzumab-deruxtecan (T-Dxd). Since the potential proportion of breast cancer patients that may benefit from these novel agents are reported to be around 39% to 79%, investigating the role of HER2-low has been a topic of interest. By analyzing the outcomes of over 2500 patients, we discovered that those with HER2-low TNBC typically experience better survival rates than HER2-0 TNBC. This difference was especially significant in postmenopausal women. These findings suggest a potential re-evaluation of how TNBC is classified and treated, highlighting the importance of identifying HER2-low expression for improving personalized treatment strategies and patient care. TNBC is noted for its aggressive behavior and poor prognosis. Recently developed HER2 target agents have shown potential benefit even in HER2-low expressing breast cancers. This study retrospectively analyzed 2542 non-metastatic TNBC patients from 2008 to 2020, revealing that 26.0% were HER2-low. Data on demographics, tumor characteristics, pathologic complete response (pCR) rates and disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed. The HER2-low group, compared to the HER2-0 group, showed significantly better DFS, DMFS, OS, BCSS (p = 0.0072, p = 0.0096, p = 0.0180, and p = 0.0001, respectively) with older age and higher rates of postmenopausal status (p < 0.0001). No significant differences in pCR rates were observed. Multivariate analyses identified HER2 status as a significant prognostic factor for DFS (p = 0.048), DMFS (p = 0.018), OS (p = 0.049), and BCSS (p = 0.008). Subgroup analysis revealed that these effects varied with menopausal status, showing more pronounced benefits in postmenopausal women. Our findings suggest that HER2-low TNBC patients exhibit a distinct clinical profile and improved survival compared to HER2-0 TNBC patients, especially in postmenopausal patients. Further research on estrogen and HER2 interaction is needed. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Migratory Tumor Cells Cooperate with Cancer Associated Fibroblasts in Hormone Receptor-Positive and HER2-Negative Breast Cancer.

Author

Joo, Eun Hye, Kim, Sangmin, Park, Donghyun, Lee, Taeseob, Park, Woong-Yang, Han, Kyung Yeon, and Lee, Jeong Eon

Subjects
BREAST cancer, FIBROBLASTS, CANCER cells, HORMONE therapy, LANDSCAPE architecture, DNA sequencing
Abstract

Hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-BC) is the most common type with a favorable prognosis under endocrine therapy. However, it still demonstrates unpredictable progression and recurrences influenced by high tumoral diversity and microenvironmental status. To address these heterogeneous molecular characteristics of HR+/HER2-BC, we aimed to simultaneously characterize its transcriptomic landscape and genetic architecture at the same resolution. Using advanced single-cell RNA and DNA sequencing techniques together, we defined four distinct tumor subtypes. Notably, the migratory tumor subtype was closely linked to genomic alterations of EGFR, related to the tumor-promoting behavior of IL6-positive inflammatory tumor-associated fibroblast, and contributing to poor prognosis. Our study comprehensively utilizes integrated analysis to uncover the complex dynamics of this breast cancer subtype, highlighting the pivotal role of the migratory tumor subtype in influencing surrounding cells. This sheds light on potential therapeutic targets by offering enhanced insights for HR+/HER2-BC treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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34. The Effects of National Insurance Coverage Expansion and Genetic Counseling's Role on BRCA1/2 Mutation Tests in Breast Cancer Patients.

Author

Jang, Sung Yoon, Kwak, Youngji, Choi, Joon Young, Shin, Dong Seung, Lee, Hyunjun, Kim, Mina, Jung, Boo Yeon, Chae, Byung Joo, Yu, Jonghan, Lee, Jeong Eon, Kim, Seok Won, Nam, Seok Jin, and Ryu, Jai Min

Subjects
BREAST tumor diagnosis, HEALTH services accessibility, INSURANCE, BRCA genes, RESEARCH funding, RETROSPECTIVE studies, TERTIARY care, CANCER patients, GENETIC counseling, TREATMENT effectiveness, GENETIC counselors, GENETIC mutation, EARLY diagnosis, INDIVIDUALIZED medicine, PATIENT aftercare, GENETIC testing
Abstract

Simple Summary: This research investigates the effects of South Korea's national insurance coverage (NIC) expansion and the inclusion of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. By analyzing data from the Samsung Medical Center, the study reveals a notable increase in testing rates following NIC expansion and the addition of genetic counselors. Particularly noteworthy is the rise in testing rates among triple-negative breast cancer (TNBC) patients under 60. Additionally, the involvement of genetic counselors led to a significant increase in follow-up patients undergoing testing. The NIC expansion also broadened insurance coverage for TNBC patients, thereby enhancing testing accessibility. These findings underscore the positive impact of NIC expansion and genetic counselor involvement on improving patient management. Addressing financial barriers to testing and integrating genetic counseling into healthcare practices present promising strategies for advancing early detection and tailored treatment approaches, thereby contributing to global efforts in cancer care and management. Purpose: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. Materials and Methods: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. Results: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. Conclusion: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts. [ABSTRACT FROM AUTHOR]

Published
2024
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