Potential Perturbations of Critical Cancer-regulatory Genes in TripleNegative Breast Cancer Cells Within the Humanized Microenvironment of Patient-derived Xenograft Models / 한국유방암학회지

Purpose@#In this study, we aimed to establish humanized patient-derived xenograft (PDX) models for triple-negative breast cancer (TNBC) using cord blood (CB) hematopoietic stem cells (HSCs). Additionally, we attempted to characterize the immune microenvironment of the humanized PDX model to understand the potential implications of altered tumorimmune interactions in the humanized PDX model on the behavior of TNBC cells. @*Methods@#To establish a humanized mouse model, high-purity CD34+ HSCs from CB were transplanted into immunodeficient NOD scid γ mice. Peripheral and intratumoral immune cell compositions of humanized and non-humanized mice were compared. Additionally, RNA sequencing of the tumor tissues was performed to characterize the gene expression features associated with humanization. @*Results@#After transplanting the CD34+ HSCs, CD45+ human immune cells appeared within five weeks. A humanized mouse model showed viable human immune cells in the peripheral blood, lymphoid organs, and in the tumor microenvironment. Humanized TNBC PDX models showed varying rates of tumor growth compared to that of non-humanized mice.RNA sequencing of the tumor tissue showed significant alterations in tumor tissues from the humanized models. tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) is a shared downregulated gene in tumor tissues from humanized models. Silencing of TNFRSF11B in TNBC cell lines significantly reduced cell proliferation, migration, and invasion in vitro. Additionally, TNFRSF11B silenced cells showed decreased tumorigenicity and metastatic capacity in vivo. @*Conclusion@#Humanized PDX models successfully recreated tumor-immune interactions in TNBC. TNFRSF11B, a commonly downregulated gene in humanized PDX models, may play a key role in tumor growth and metastasis. Differential tumor growth rates and gene expression patterns highlighted the complexities of the immune response in the tumor microenvironment of humanized PDX models.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial / 한국유방암학회지

Purpose@#Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. @*Methods@#The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The coronavirus disease 2019 (COVID-19) outbreak has significantly impacted the diagnosis and treatment of breast cancer. Our study investigated the change in diagnosis and treatment of breast cancer with the progress of COVID-19 pandemic. @*Materials and Methods@#The study group comprised 6,514 recently diagnosed breast cancer patients between January 1, 2019, and February 28, 2021. The patients were divided into two groups: pre–COVID-19 period (3,182; January 2019 to December 2019) and COVID-19 pandemic period (3,332; January 2020 to February 2021). Clinicopathological information related to the first treatment after breast cancer diagnosis was retrospectively collected and analyzed in the two groups. @*Results@#Among the 6,514 breast cancer patients, 3,182 were in the pre–COVID-19 period and 3,332 were in the COVID-19 pandemic period. According to our evaluation, the least breast cancer diagnosis (21.8%) was seen in the first quarter of 2020. The diagnosis increased gradually except for the fourth quarter in 2020. While early-stage breast cancer was diagnosed 1,601 (48.1%) during the COVID-19 pandemic (p=0.001), the number of surgical treatments increased 4.6% (p < 0.001), and the treatment time was slightly shorter 2 days (p=0.001). The breast cancer subtype distribution was not statistically different between the pre–COVID-19 and COVID-19 period groups. @*Conclusion@#In the early stages of the pandemic, the number of breast cancer cases temporarily decreased; however, they stabilized soon, and no significant differences could be identified in the diagnosis and treatment when compared to the period before the pandemic.

Life-Threatening Hematoma in an Elderly Breast Cancer Patient Undergoing Chemotherapy / 한국유방암학회지

The use of neoadjuvant chemotherapy in older patients is increasing. However, chemotherapy should be administered considering the medical comorbidities of the patients and the toxicity of chemotherapeutic agents. Here, we present a case of abdominal wall hematoma with spontaneous inferior epigastric artery injury caused by coughing in a 70-year-old woman who was treated with neoadjuvant chemotherapy. Abdominal computed tomography demonstrated an abdominal wall hematoma with active bleeding. However, angiography with selective embolization of the right inferior epigastric artery and the right internal mammary artery was performed successfully. Scheduled chemotherapy was discontinued over concerns of rebleeding and breast-conserving surgery was performed. When deciding on chemotherapy for older patients, attention should be paid to the various complications.

Residual Risk of Ipsilateral Tumor Recurrence in Patients Who Achieved Clear Lumpectomy Margins After Repeated Resection / 한국유방암학회지

Purpose@#Patients with breast cancer with positive lumpectomy margins have a two-fold increased risk of ipsilateral breast tumor recurrence (IBTR). This can be the result of either technically incomplete resection or the biological characteristics of the tumor that lead to a positive margin. We hypothesized that if achieving negative margins by re-excision nullifies the IBTR risk, then the increased risk is mainly attributed to the technical incompleteness of the initial surgeries. Thus, we investigated IBTR rates in patients with breast cancer who achieved clear margins after re-excision. @*Methods@#We retrospectively reviewed patients who underwent breast lumpectomy for invasive breast cancer between 2004 and 2018 at a single institution, and investigated IBTR events. @*Results@#Among 5,598 patients, 793 achieved clear margins after re-excision of their initial positive margins. During the median follow-up period of 76.4 months, 121 (2.2%) patients experienced IBTR. Patients who underwent re-excision to achieve negative margin experienced significantly higher IBTR rates compared to those achieving clear margin at first lumpectomy (10-year IBTR rate: 5.3% vs. 2.6% [25 vs. 84 events]; unadjusted p = 0.031, hazard ratio, 1.61, 95% confidence interval [CI], 1.04–2.48; adjusted p = 0.030, hazard ratio, 1.69, 95% CI, 1.05–2.72). This difference was more evident in patients aged < 50 years and those with delayed IBTR. Additionally, no statistically significant differences were observed in the spatial distribution of IBTR locations. @*Conclusion@#Patients who underwent re-excision for initial positive margins had an increased risk of IBTR, even after achieving a final negative margin, compared to patients with negative margins initially. This increased risk of IBTR is mostly observed in young patients and delayed cases.

AKR1C2 Promotes Metastasis and Regulates the Molecular Features of Luminal Androgen Receptor Subtype in Triple Negative Breast Cancer Cells / 한국유방암학회지

Purpose@#Patients with triple-negative breast cancer (TNBC) have an increased risk of distant metastasis compared to those with other subtypes. In this study, we aimed to identify the genes associated with distant metastasis in TNBC and their underlying mechanisms. @*Methods@#We established patient-derived xenograft (PDX) models using surgically resected breast cancer tissues from 31 patients with TNBC. Among these, 15 patients subsequently developed distant metastases. Candidate metastasis-associated genes were identified using RNA sequencing. In vitro wound healing, proliferation, migration, and invasion assays and in vivo tumor xenograft and metastasis assays were performed to determine the functional importance of aldo-keto reductase family 1 member C2 (AKR1C2). Additionally, we used the METABRIC dataset to investigate the potential role of AKR1C2 in regulating TNBC subtypes and their downstream signaling activities. @*Results@#RNA sequencing of primary and PDX tumors showed that genes involved in steroid hormone biosynthesis, including AKR1C2, were significantly upregulated in patients who subsequently developed metastasis. In vitro and in vivo assays showed that silencing of AKR1C2 resulted in reduced cell proliferation, migration, invasion, tumor growth, and incidence of lung metastasis. AKR1C2 was upregulated in the luminal androgen receptor (LAR) subtype of TNBC in the METABRIC dataset, and AKR1C2 silencing resulted in the downregulation of LAR classifier genes in TNBC cell lines. The androgen receptor (AR) gene was a downstream mediator of AKR1C2-associated phenotypes in TNBC cells. AKR1C2 expression was associated with gene expression pathways that regulate AR expression, including JAK-STAT signaling or interleukin 6 (IL-6). The levels of phospho-signal transducer and activator of transcription and IL-6, along with secreted IL-6, were significantly downregulated in AKR1C2-silenced TNBC cells. @*Conclusion@#Our data indicate that AKR1C2 is an important regulator of cancer growth and metastasis in TNBC and may be a critical determinant of LAR subtype features.

Retrospective Cohort Study on the Long-term Oncologic Outcomes of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope Mapping) in Early Breast Cancer: A Propensity Score-Matched Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In sentinel lymph node (SLN) biopsy (SLNB) during breast cancer surgery, SLN mapping using dye and isotope (DUAL) may have lower false-negative rates than the dye-only (DYE) method. However, the long-term outcomes of either method are unclear. We aimed to compare long-term oncological outcomes of DYE and DUAL for SLNB in early breast cancer. @*Materials and Methods@#This retrospective single-institution cohort study included 5,795 patients (DYE, 2,323; DUAL, 3,472) with clinically node-negative breast cancer who underwent SLNB and no neoadjuvant therapy. Indigo carmine was used for the dye method and Tc99m-antimony trisulfate for the isotope. To compare long-term outcomes, pathologic N0 patients were selected from both groups, and propensity score matching (PSM), considering age, pT category, breast surgery, and adjuvant treatment, was performed (1,441 patients in each group). @*Results@#The median follow-up duration was 8.7 years. The median number of harvested sentinel nodes was 3.21 and 3.12 in the DYE and DUAL groups, respectively (p=0.112). The lymph node–positive rate was not significantly different between the two groups in subgroups of similar tumor sizes (p > 0.05). Multivariate logistic regression revealed that the mapping method was not significantly associated with the lymph node–positive rate (p=0.758). After PSM, the 5-year axillary recurrence rate (DYE 0.8% vs. DUAL 0.6%, p=0.096), and 5-year disease-free survival (DYE 93.9% vs. DUAL 93.7%, p=0.402) were similar between the two groups. @*Conclusion@#Dye alone for SLNB was not inferior to dual mapping regarding long-term oncological outcomes in early breast cancer.

Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells / 한국유방암학회지

Purpose@#Chromosomal instability (CIN) contributes to intercellular genetic heterogeneity and has been implicated in paclitaxel (PTX) resistance in breast cancer. In this study, we explored polo-like kinase 1 (PLK1) as an important regulator of mitotic integrity and as a useful predictive biomarker for PTX resistance in breast cancer. @*Methods@#We performed PTX resistance screening using the human kinome CRISPR/ Cas9 library in breast cancer cells. In vitro cell proliferation and apoptosis assays and in vivo xenograft experiments were performed to determine the effects of PLK1 on breast cancer cells. Immunofluorescence microscopy was used to measure the degree of multipolar cell division. @*Results@#Kinome-wide CRISPR/Cas9 screening identified various kinases involved in PTX resistance in breast cancer cells; among these, PLK1 was chosen for further experiments.PLK1 knockdown inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells in vitro and in vivo. Moreover, PLK1 silencing sensitized breast cancer cells and mouse xenograft tumor models to PTX cytotoxicity. Silencing of PLK1 induced the formation of multipolar spindles and increased the percentage of multipolar cells. In addition, PLK1 silencing resulted in the downregulation of BubR1 and Mad2 in breast cancer cells. Furthermore, PLK1 upregulation in primary breast cancer was associated with decreased overall patient survival based on the analysis of The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium databases. @*Conclusion@#PLK1 plays an important role in PTX resistance by regulating CIN in breast cancer cells. Targeting PLK1 may be an effective treatment strategy for PTX-resistant breast cancers.

Association between Number of Retrieved Sentinel Lymph Nodes and Breast Cancer-related Lymphedema / 한국유방암학회지

Purpose@#Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. @*Methods@#Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. @*Results@#Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). @*Conclusion@#The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

Association between Number of Retrieved Sentinel Lymph Nodes and Breast Cancer-related Lymphedema / 한국유방암학회지

Purpose@#Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. @*Methods@#Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. @*Results@#Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). @*Conclusion@#The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Erratum: A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer / 한국유방암학회지

In the article, “A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer” in Volume 22(4), page 579-586 was error in the table. In Table 1, the value of pN0 was incorrectly listed as 29 (56.9) in ‘diagnosed as normal by biomarker’ and corrected to 39 (76.5). The authors apologize for any inconvenience that this may have caused.

A survey investigating the current situation of the international visiting scholar program at the department of surgery in Korea

Purpose@#The number of international visiting scholars has been on the increase in Korea and we aim to investigate the program’s current situation. @*Methods@#This cross-sectional study is based on an online survey questionnaire responded by international visiting scholars in surgical departments of 8 Korean hospitals between 2014 and 2018 about their experiences and satisfaction with the visiting scholar program. @*Results@#A total of 1,496 international scholars from 80 countries visited various surgical departments in 8 Korean hospitals between 2014 and 2018. The numbers have been on the increase over the years. Out of 355 visiting scholars in 2018, 71 replied to the online survey, of whom 52 were male and 19 female, and mostly in their 30s and 40s. Information about the program was accessed mostly through friends or colleagues (42.3%) and international conferences (36.6%). The commonest funding source was private (35.2%) and more than half stayed for less than 3 months. The visiting scholar’s main roles were mostly observation or participation in surgery and clinical research. All but 1 were satisfied with the program (98.6%) and would recommend it to friends and colleagues, although the language barrier was identified as an inconvenience. Those aged 20–39 years with governmental or institutional funding were associated with stays of more than 1 year. @*Conclusion@#The number of international visiting scholars at surgical departments in Korean hospitals has been on the increase with high satisfaction levels. Improvements need to be made on funding sources and lengthening visiting period to maximize the benefits of the program.

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). @*Materials and Methods@#A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. @*Results@#Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. @*Conclusion@#NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Prognostic Role of Androgen Receptor Expression in Surgically Resected Early Breast Cancer Patients / 한국유방암학회지

Purpose@#Endocrine therapy is a standard treatment for hormone receptor-positive breast cancer, which accounts for 60%–75% of all breast cancer. Hormone receptor positivity is a prognostic and predictive biomarker in breast cancer. Approximately 50%–80% of breast cancer is also positive for androgen receptor (AR), but the prognostic and predictive value of AR expression in breast cancer is controversial. Here, we investigated AR expression and its prognostic value in patients with surgically resected breast cancer in Korea. @*Methods@#We retrospectively reviewed the medical records of patients who had surgically resected breast cancer to collect AR expression data and other clinicopathological data. The optimal cut-off for AR positivity was determined using a receiver operating characteristic curve analysis. @*Results@#We reviewed 957 patients with surgically resected breast cancer from June 2012 to April 2013. The median follow-up was 62 months, and relapse events occurred in 101 (10.6%) patients. Unlike the cut-off value of 1% or 10% in previous reports, 35% was determined to be best for predicting relapse-free survival (RFS) in this study. At the cut-off value of 35%, 654 (68.4%) patients were AR-positive. AR expression was more prevalent in luminal A (87.6%) and luminal B (73.1%) types than in human epidermal growth factor receptor 2-positive (56.2%) or triple-negative (20.6%) types. AR expression of ≥ 35% was significantly related to longer RFS in a multivariate analysis (hazard ratio, 0.430; 95% confidence interval, 0.260–0.709; p = 0.001). @*Conclusion@#We propose a cut-off value of 35% to best predict RFS in patients with surgically resected breast cancer. AR expression was positive in 68.4% of patients, and AR positivity was found to be an independent prognostic factor for longer RFS.

Protein Phosphatase 1H, Cyclin-Dependent Kinase Inhibitor p27, and Cyclin-Dependent Kinase 2 in Paclitaxel Resistance for Triple Negative Breast Cancers / 한국유방암학회지

Purpose@#Paclitaxel is a cytotoxic chemotherapy commonly used in patients with triple negative breast cancer (TNBC); however, the resistance to paclitaxel is a cause of poor response in the patients. The aim of this study was to examine the role of protein phosphatase 1H (PPM1H) in paclitaxel resistance in breast cancer patients. @*Methods@#To investigate the function of PPM1H in paclitaxel treatment, we conducted in vitro assays and molecular experiments using a stable cell line (MDA-MB-231) in which PPM1H is overexpressed. We also performed molecular analyses on patient tissue samples. Molecular expression related to PPM1H in breast cancer patients was analyzed using TCGA data. @*Results@#We investigated whether PPM1H was associated with paclitaxel resistance in breast cancer. PPM1H expression was upregulated in breast cancer cells treated with paclitaxel. We also observed that overexpression of PPM1H in breast cancer cells resulted in increased sensitivity to paclitaxel in vitro. Additionally, paclitaxel treatment induced dephosphorylation of cyclin-dependent kinase (CDK) inhibitor p27 (p27), which was more evident in PPM1H-overexpressing cells. To understand how upregulation of PPM1H increases paclitaxel sensitivity, we determined the levels of p27, phospho-p27, and CDK2, since CDK2 exerts antagonistic effects against PPM1H on p27 phosphorylation. The patient-derived xenograft (PDX) tumors that did not respond to paclitaxel showed increased levels of CDK2 and phospho-p27 and decreased levels of total p27 compared to the other breast tumor tissues. The use of dinaciclib, a selective CDK inhibitor, significantly inhibited tumor growth in the PDX model. @*Conclusion@#CDK2 kinase activity was significantly upregulated in basal breast cancer tumors and was negatively correlated with p27 protein levels in the TCGA breast cancer dataset, suggesting that targeting CDK2 may be an effective treatment strategy for TNBC patients.

Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer / 한국유방암학회지

Immediate Breast Reconstruction vs. Mastectomy Alone in Locally Advanced Breast Cancer; Local Recurrence and Distant Recurrence

PURPOSE@#The oncologic safety of immediate breast reconstruction (IBR) has been demonstrated. However, the outcome of IBR for locally advanced breast cancer (LABC) is still under debate. We compared the survival outcome of LABC patients who underwent IBR vs. mastectomy alone.@*METHODS@#We retrospectively analyzed a total of 248 patients with stage III breast cancer who were treated with mastectomy between 2004 and 2015. The study subjects were divided into 2 groups: patients who received IBR (n=77) or mastectomy alone (MA) (n=171). We compared disease-free survival (DFS) of both groups.@*RESULTS@#Median follow-up duration was 49 months and the mean age of patients was 49 years. Patients in the IBR group were significantly younger and had lower body mass index (BMI) than those in the MA group. In a univariate analysis, IBR group showed better DFS than the MA group (DFS 81.3 months vs. 49.8 months, p<0.001). There was no delay in adjuvant treatment in the IBR group. In a multivariate analysis, IBR was associated with better DFS (hazard ratio (HR) for recurrence: 0.37, 95% CI 0.20–0.69, p=0.002) when adjusted for potential prognostic factors. In a subgroup analysis performed according to disease stage (IIIA and IIIB/IIIC), DFS was significantly better in IBR than MA group in both stage subgroups (p<0.001).@*CONCLUSION@#We demonstrated that patients who underwent IBR showed better DFS outcome compared with patients who underwent mastectomy alone. Our results can help surgeons to determine if IBR is an option in patients with LABC.

Efficacy of Mastocheck for Screening of Early Breast Cancer: Comparison with Screening Mammography

PURPOSE@#This study was designed to verify the effectiveness of Mastocheck, a new diagnostic tool developed with proteomics techniques using plasma proteins. In addition, checked the current state of mammography used for breast cancer screening.@*METHODS@#A total of 305 cases were analyzed (normal 122, breast cancer 183) and used for validation after Mastocheck development. First, screening mammograms of normal patients and pre-diagnosis mammography of cancer patients were reviewed retrospectively. The results were compared with Mastocheck, a newly developed blood test. Imaging tests were blinded and analyzed by dividing the readings of breast specialists and non-breast specialists among radiologists. We confirmed how much better the results would be if only the mammography was used and if both tests were used together.@*RESULTS@#The sensitivity, specificity, and accuracy of mammography alone, reviewed by non-breast specialists among radiologists, were 63.0%, 85.7%, and 71.3%, respectively. In dense breasts, the values were 59.2%, 84.8% and 69.0%, which were too low to be considered interpretable. The sensitivity, specificity and accuracy of the test was 93.9%, 83.8%, and 90.2% when using mammography and Mastocheck together. From these results, an improvement in sensitivity of about 30% and an improvement in accuracy of about 15% or more in concomitant use than mammography alone can be seen.@*CONCLUSION@#Mastocheck can be widely used for screening breast cancer, especially in dense breasts, patients with low accuracy in mammography, and patients with mammography side effects. In addition, it has the advantage of increasing the diagnosis rate when used with mammography, the current screening method of choice.