Publications by authors named "Dong-Young Noh"

398 Publications

Correction: Enhanced anti-tumor activity and cytotoxic effect on cancer stem cell population of metformin-butyrate compared with metformin HCl in breast cancer.

Oncotarget 2021 Jun 8;12(12):1197-1198. Epub 2021 Jun 8.

Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.

[This corrects the article DOI: 10.18632/oncotarget.9522.].
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http://dx.doi.org/10.18632/oncotarget.27986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202778PMC
June 2021

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (-2df = 1.2 × 10). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (-2df = 1.1 × 10). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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http://dx.doi.org/10.3390/cancers13102370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156547PMC
May 2021

Transformation of the Patient and Society: A Patient Survivors' Group and Breast Cancer Awareness Campaign.

Authors:
Dong-Young Noh

Adv Exp Med Biol 2021 ;1187:625-630

Department of Surgery, College of Medicine, Seoul National University, Seoul, South Korea.

Most biomedical research has the same goal: to make human lives better and healthier. However, sometimes doctors forget their own mission while treating disease. Physicians should remember the old adage to treat the patient, not the disease. The doctor-patient relationship used to be a one-way affair, going from the doctor to the patient. Compared with doctors, society expects relatively little in terms of roles and duties from patients as well as the rest of the population. Thus, society could be a foundational place in which doctors, patients, and research can communicate with one another, or society itself could transform each of these components. The best way for physicians to provide better care is to listen to the needs of patients and society more broadly. We must reflect on whether this kind of transformation is happening in our current society.
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http://dx.doi.org/10.1007/978-981-32-9620-6_34DOI Listing
May 2021

Phospholipase Signaling in Breast Cancer.

Adv Exp Med Biol 2021 ;1187:23-52

School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.

Breast cancer progression results from subversion of multiple intra- or intercellular signaling pathways in normal mammary tissues and their microenvironment, which have an impact on cell differentiation, proliferation, migration, and angiogenesis. Phospholipases (PLC, PLD and PLA) are essential mediators of intra- and intercellular signaling. They hydrolyze phospholipids, which are major components of cell membrane that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid. Enzymatic processing of phospholipids by phospholipases converts these molecules into lipid mediators that regulate multiple cellular processes, which in turn can promote breast cancer progression. Thus, dysregulation of phospholipases contributes to a number of human diseases, including cancer. This review describes how phospholipases regulate multiple cancer-associated cellular processes, and the interplay among different phospholipases in breast cancer. A thorough understanding of the breast cancer-associated signaling networks of phospholipases is necessary to determine whether these enzymes are potential targets for innovative therapeutic strategies.
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http://dx.doi.org/10.1007/978-981-32-9620-6_2DOI Listing
May 2021

Translational Research in Surgical Oncology: Introduction and My Own Experience as a Surgeon-Scientist.

Authors:
Dong-Young Noh

Adv Exp Med Biol 2021 ;1187:3-20

Department of Surgery, College of Medicine, Seoul National University, Seoul, South Korea.

Translational research is possible when scientists have broad knowledge of not only basic research, but also clinical science, which is acquired via experience in patient care. These requirements cannot always be met by one individual, and, hence, collaboration between suitably qualified individuals is the key for the progress of translational research. However, it is vital that translational research is conducted by an investigator who has knowledge about all fields. I could be a good conductor in that sense, because as an oncology surgeon, I have considerable experience in working with patients; in addition, I have a background in biochemistry and have started my basic research laboratory. Thus, I can use these qualifications to my advantage to build a tissue bank as the first step, and initiate small-scale experiments such as estimating the DNA or protein levels in specific tissues or blood samples. Once I successfully launch good research products and publish in peer-reviewed journals, I intend to build a large research group focusing on large-scale studies on single nucleotide polymorphisms and proteomics. These translational approaches can overcome several unsolved clinical problems. Many of my research products, for example, patents and new techniques such as [email protected], are designed for improving the clinical outcomes in patients.
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http://dx.doi.org/10.1007/978-981-32-9620-6_1DOI Listing
May 2021

The Emotional Status, Attitudes in Decision-Making Process, and Their Impact on Surgical Choices in Korean Breast Cancer Patients.

J Oncol 2021 12;2021:6636986. Epub 2021 Mar 12.

Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

Purpose: We examined the incidence of emotional distress in women with newly diagnosed breast cancer to determine whether the degree of emotional distress affected their choice of breast-conserving surgery (BCS) or mastectomy and evaluated how the patient's preferred role in decision-making influenced her choice of surgical method.

Methods: This prospective study included 85 patients newly diagnosed with in situ or invasive breast cancer eligible for BCS. Their degree of depression/anxiety and attitude toward the decision-making process were measured using the Hospital Anxiety and Depression Scale (HADS) and Control Preference Scale (CPS), respectively. After receiving information on both surgical methods, the patients indicated their preferred surgical method and completed the CPS at their initial and second visits before surgery.

Results: After the diagnosis of breast cancer, 75.3% of patients showed abnormal or borderline HADS scores for depression and 41.2% for anxiety. Patients with borderline or abnormal degrees of depression were more likely to have coexisting abnormal degrees of anxiety ( < 0.001). However, the presence of depression or anxiety was not associated with patients' surgical choices (=0.394 and 0.530, respectively). Patients who preferred a more active role in the decision-making process were more likely to choose mastectomy over BCS, while those who were passive or collaborative chose BCS more frequently (=0.001).

Conclusion: Although many patients with newly diagnosed breast cancer experience depression and anxiety before surgery, these do not affect the choice of surgical method; however, their attitudes toward the decision-making process do.
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http://dx.doi.org/10.1155/2021/6636986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984876PMC
March 2021

Nutrient intakes from supplement and factors associated with supplement use among breast cancer survivors: A cross-sectional study.

Eur J Cancer Care (Engl) 2021 Sep 28;30(5):e13447. Epub 2021 Mar 28.

Department of Food and Nutrition, Seoul National University, Seoul, Korea.

Objective: We investigated the contribution of supplement use to total nutrient intake, the prevalence of inadequate nutrient intake and the factors associated with supplement use among breast cancer survivors.

Methods: A total of 701 Korean breast cancer survivors were included. We calculated the contribution of dietary supplements to total nutrient intake and the proportion of the population below the estimated average requirements (EARs) or exceeding the tolerable upper intake levels (ULs). Stepwise logistic regression was used to identify factors associated with dietary supplement use.

Results: A total of 66.5% of the survivors used dietary supplements, with multivitamins and minerals being the most commonly consumed ones. The per cent contribution of supplement to the total intake was the highest for vitamin C. 28.2%-55.4% of the non-users consumed below the EAR of riboflavin, folate and calcium; 6.1%, 4.9% and 6.5% of the supplement users consumed above the UL of vitamins A and C, and iron, respectively. Supplement users had higher education levels or longer survival time.

Conclusion: 66.5% of Korean breast cancer survivors used dietary supplements. A higher education level or prolonged survival time was associated with higher use of dietary supplements.
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http://dx.doi.org/10.1111/ecc.13447DOI Listing
September 2021

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

J Breast Cancer 2021 Feb;24(1):63-74

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

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 ( < 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, =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.
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http://dx.doi.org/10.4048/jbc.2021.24.e9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920859PMC
February 2021

Intensity of metastasis screening and survival outcomes in patients with breast cancer.

Sci Rep 2021 Feb 2;11(1):2851. Epub 2021 Feb 2.

Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Previous randomized trials, performed decades ago, showed no survival benefit of intensive screening for distant metastasis in breast cancer. However, recent improvements in targeted therapies and diagnostic accuracy of imaging have again raised the question of the clinical benefit of screening for distant metastasis. Therefore, we investigated the association between the use of modern imaging and survival of patients with breast cancer who eventually developed distant metastasis. We retrospectively reviewed data of 398 patients who developed distant metastasis after their initial curative treatment between January 2000 and December 2015. Patients in the less-intensive surveillance group (LSG) had significantly longer relapse-free survival than did patients in the intensive surveillance group (ISG) (8.7 vs. 22.8 months; p = 0.002). While the ISG showed worse overall survival than the LSG did (50.2 vs. 59.9 months; p = 0.015), the difference was insignificant after adjusting for other prognostic factors. Among the 225 asymptomatic patients whose metastases were detected on imaging, the intensity of screening did not affect overall survival. A small subgroup of patients showed poor survival outcomes when they underwent intensive screening. Patients with HR-/HER2 + tumors and patients who developed lung metastasis in the LSG had better overall survival than those in the ISG did. Highly intensive screening for distant metastasis in disease-free patients with breast cancer was not associated with significant survival benefits, despite the recent improvements in therapeutic options and diagnostic techniques.
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http://dx.doi.org/10.1038/s41598-021-82485-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854644PMC
February 2021

Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium.

Cancer Epidemiol Biomarkers Prev 2021 04 26;30(4):623-642. Epub 2021 Jan 26.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype ( > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026532PMC
April 2021

S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell-cell interactions with adjacent breast cancer cells.

Sci Rep 2021 01 14;11(1):1337. Epub 2021 Jan 14.

Center for Medical Innovation, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell-cell interactions between the MCF10A cells and breast cancer cells including lamellipodia or nanotube-like contacts and transfer of extracellular vesicles. Co-cultured MCF10A cells exhibited features of epithelial-mesenchymal transition, and showed increased capacity of cell proliferation, migration, colony formation, and 3-dimensional sphere formation. Direct co-culture showed most distinct phenotype changes in MCF10A cells followed by conditioned media treatment and indirect co-culture. Transcriptome analysis and phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated in MCF10A cells after the direct co-culture with breast cancer cells. S100A8 and S100A9 showed distinct up-regulation in the co-cultured MCF10A cells and their microenvironmental upregulation was also observed in the orthotropic xenograft of syngeneic mouse mammary tumors. When S100A8/A9 overexpression was induced in MCF10A cells, the cells showed phenotypic features of directly co-cultured MCF10A cells in terms of in vitro cell behaviors and signaling activities suggesting a S100A8/A9-mediated transition program in non-tumorigenic epithelial cells. This study suggests the possibility of dynamic cell-cell interactions between non-tumorigenic mammary epithelial cells and breast cancer cells that could lead to a substantial transition in molecular and functional characteristics of mammary epithelial cells.
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http://dx.doi.org/10.1038/s41598-020-80625-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809201PMC
January 2021

STAT3 Stabilizes IKKα Protein through Direct Interaction in Transformed and Cancerous Human Breast Epithelial Cells.

Cancers (Basel) 2020 Dec 30;13(1). Epub 2020 Dec 30.

Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) are two representative transcription factors that play a critical role in inflammation-associated tumorigenesis through multi-level cooperation. Unlike other types of tumors, breast carcinomas have shown a significant dependency on the non-classical NF-κB pathway as well as the classical one. The α subunit of the inhibitor of the κB kinase (IKK) complex, IKKα, is involved in both classical and non-classical activation of NF-κB. Although the cross-talk between STAT3 and NF-κB has been suggested in several studies, the interplay between STAT3 and the regulators of NF-κB including IKKα has not been fully clarified yet. In this study, we observed overexpression and co-localization of IKKα and STAT3 in human breast cancer tissues as well as in H- transformed human breast epithelial (H- MCF-10A) and breast cancer (MDA-MB-231) cells. By utilizing small interfering RNA (siRNA) technology, we were able to demonstrate that STAT3 up-regulated IKKα, but not IKKβ or IKKγ, in these cells. This was attributable to direct binding to and subsequent stabilization of IKKα protein by blocking the ubiquitin-proteasome system. Notably, we identified the lysine 44 residue of IKKα as a putative binding site for STAT3. Moreover, siRNA knockdown of attenuated viability, anchorage-independent growth and migratory capabilities of H- MCF-10A cells. Taken together, these findings propose a novel mechanism responsible for NF-κB activation by STAT3 through stabilization of IKKα, which contributes to breast cancer promotion and progression. Thus, breaking the STAT3-IKKα alliance can be an alternative therapeutic strategy for the treatment of breast cancer.
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http://dx.doi.org/10.3390/cancers13010082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795115PMC
December 2020

Interaction of Nrf2 with dimeric STAT3 induces IL-23 expression: Implications for breast cancer progression.

Cancer Lett 2021 03 3;500:147-160. Epub 2020 Dec 3.

Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea; Cancer Research Institute, Seoul National University, Seoul, 03080, South Korea. Electronic address:

Persistent activation of STAT3 and Nrf2 is considered to stimulate the aggressive behavior of basal-like breast cancer (BLBC). However, the precise mechanism underlying sustained overactivation of these transcription factors and their roles in breast cancer progression remain elusive. Analysis of the TCGA multi-omics data showed that high levels of STAT3 and Nrf2 mRNA were correlated with elevated expression of P-STAT3 and Nrf2 target proteins in breast cancer patients. Our present study demonstrates a unique interaction between Nrf2 and STAT3 in the maintenance and progression of BLBC. RNA sequencing analysis identified the gene encoding IL-23A upregulated by concurrent binding of STAT3 and Nrf2 to its promoter. IL-23A depletion also showed the similar phenotypic changes to those caused by double knockdown of both transcription factors. In conclusion, the STAT3-Nrf2 interaction accelerates BLBC growth and progression by augmenting IL-23A expression, which underscores the importance of subtype-specific molecular pathways in human breast cancer.
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http://dx.doi.org/10.1016/j.canlet.2020.11.047DOI Listing
March 2021

Development and Validation of a Next-Generation Sequencing-Based Multigene Assay to Predict the Prognosis of Estrogen Receptor-Positive, HER2-Negative Breast Cancer.

Clin Cancer Res 2020 12 7;26(24):6513-6522. Epub 2020 Oct 7.

Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

Purpose: Multigene assays provide useful prognostic information regarding hormone receptor (HR)-positive breast cancer. Next-generation sequencing (NGS)-based platforms have numerous advantages including reproducibility and adaptability in local laboratories. This study aimed to develop and validate an NGS-based multigene assay to predict the distant recurrence risk.

Experimental Design: In total, 179 genes including 30 reference genes highly correlated with the 21-gene recurrence score (RS) algorithm were selected from public databases. Targeted RNA-sequencing was performed using 250 and 93 archived breast cancer samples with a known RS in the training and verification sets, respectively, to develop the algorithm and NGS-Prognostic Score (NGS-PS). The assay was validated in 413 independent samples with long-term follow-up data on distant metastasis.

Results: In the verification set, the NGS-PS and 21-gene RS displayed 91.4% concurrence (85/93 samples). In the validation cohort of 413 samples, area under the receiver operating characteristic curve plotted using NGS-PS values classified for distant recurrence was 0.76. The best NGS-PS cut-off value predicting distant metastasis was 20. Furthermore, 269 and 144 patients were classified as low- and high-risk patients in accordance with the cut-off. Five- and 10-year estimates of distant metastasis-free survival (DMFS) for low- versus high-risk groups were 97.0% versus 77.8% and 93.2% versus 64.4%, respectively. The age-related HR for distant recurrence without chemotherapy was 9.73 (95% CI, 3.59-26.40) and 3.19 (95% CI, 1.40-7.29) for patients aged ≤50 and >50 years, respectively.

Conclusions: The newly developed and validated NGS-based multigene assay can predict the distant recurrence risk in ER-positive, HER2-negative breast cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2107DOI Listing
December 2020

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients.

Cancer Res Treat 2021 Jan 23;53(1):65-76. Epub 2020 Sep 23.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

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.
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http://dx.doi.org/10.4143/crt.2020.430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812023PMC
January 2021

Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data.

Breast 2020 Dec 19;54:25-30. Epub 2020 Aug 19.

Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea. Electronic address:

Background: Aromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen.

Methods: We analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE.

Results: We included 47,569 women for the final analysis. Patients were classified into 'No hormonal treatment (n = 18,807), 'Switch (n = 2097)', 'Tamoxifen (n = 7081)' and 'AI (n = 19,584)'. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74-0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84-1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47-0.84).

Conclusions: Our results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.
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http://dx.doi.org/10.1016/j.breast.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481564PMC
December 2020

Effect of standard low-dose anthracycline chemotherapy on late congestive heart failure in breast cancer survivors aged between 50 and 59 at diagnosis: A nationwide study.

Breast 2020 Oct 31;53:125-129. Epub 2020 Jul 31.

Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: Although chemotherapy-induced congestive heart failure (CHF) is a well-known adverse event in cancer survivors, the long-term risk of standard low-dose anthracycline has not yet been reported. This study aimed to investigate the long-term effects of standard anthracycline on late CHF in breast cancer survivors.

Materials And Methods: A nationwide retrospective cohort study was conducted using the national insurance claims data for nearly 98% of Korean citizens. Between Jan 2010 and Dec 2015, a total of 56,338 newly diagnosed female breast cancer survivors were included.

Results: The total number of person-years was 199,648 and the incidence rate of late CHF was 3.57 per 1000 person-years. In multivariate analysis according to the subject's age at diagnosis, only in the 50-59 age group, anthracycline-based [hazard ratio (HR) 1.765, 95% confidence interval (CI) 1.206-2.583] and taxane plus anthracycline-based regimens (HR 1.816, 95% CI 1.192-2.768) significantly increased the risk of late CHF. In the 50-59 age group, standard low-dose anthracycline significantly increased the risk of late CHF (HR 1.627, 95% CI 1.080-2.451) in Cox proportional hazard regression models. In competing risk model with recurrence and in-hospital death as competing risks, standard low-dose anthracycline was a significant risk factor for late CHF [subdistribution hazard ratio (SHR) 1.553, 95% CI 1.029-2.340].

Conclusion: This nationwide study showed that standard chemotherapy with low-dose anthracycline is a risk factor for late-onset CHF in breast cancer survivors who were in their 50 s at breast cancer diagnosis. Long-term monitoring of late CHF should be considered in these younger breast cancer survivors.
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http://dx.doi.org/10.1016/j.breast.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414012PMC
October 2020

H-Ras induces Nrf2-Pin1 interaction: Implications for breast cancer progression.

Toxicol Appl Pharmacol 2020 09 1;402:115121. Epub 2020 Jul 1.

Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea; Department of Molecular Medicine, Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea. Electronic address:

Aberrant activation of H-Ras is often associated with tumor aggressiveness in breast cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1  (Pin1) is a unique enzyme that interacts with phosphorylated serine or threonine of a target protein and isomerizes the adjacent proline residue. Pin1 is prevalently overexpressed in human cancers, and its overexpression correlates with poor prognosis. Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of cellular redox homeostasis. The sustained activation/accumulation of Nrf2 has been observed in many different types of human malignancies, conferring an advantage for growth and survival of cancer cells. The activated form of H-Ras (GTP-H-Ras) is highly overexpressed in human breast cancer tissues. In our present study, silencing of H-Ras decreased the invasiveness of MDA-MB-231 human breast cancer cells and abrogated the interaction between Pin1 and Nrf2 in these cells. Pin1 knockdown blocked the accumulation of Nrf2, thereby suppressing proliferation and clonogenicity of MCF10A-Ras human mammary epithelial cells. We found that Pin1 binds to Nrf2 which stabilizes this transcription factor by hampering proteasomal degradation. In conclusion, H-Ras activation in cooperation with the Pin1-Nrf2 complex represents a novel mechanism underlying breast cancer progression and constitutive activation of Nrf2 and can be exploited as a therapeutic target.
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http://dx.doi.org/10.1016/j.taap.2020.115121DOI Listing
September 2020

Prediction of pathologic complete response using image-guided biopsy after neoadjuvant chemotherapy in breast cancer patients selected based on MRI findings: a prospective feasibility trial.

Breast Cancer Res Treat 2020 Jul 16;182(1):97-105. Epub 2020 May 16.

Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Purpose: Accurate prediction of pathologic complete response (pCR) in breast cancer using magnetic resonance imaging (MRI) and ultrasound (US)-guided biopsy may aid in selecting patients who forego surgery for breast cancer. We evaluated the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after neoadjuvant chemotherapy (NAC).

Methods: After completion of NAC, 40 patients with near pCR (either tumor size ≤ 0.5 cm or lesion-to-background signal enhancement ratio (L-to-B SER) ≤ 1.6 on MRI) and no diffused residual microcalcifications were prospectively enrolled at a single institution. US-guided multiple core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. The negative predictive value (NPV), accuracy, and false-negative rate (FNR) were analyzed.

Results: pCR was confirmed in 27 (67.5%) surgical specimens. Preoperative biopsy had an NPV, accuracy, and FNR of 87.1%, 90.0%, and 30.8%, respectively. NPV for hormone receptor-negative and hormone receptor-positive tumors were 83.3% and 100%, respectively. Obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI (27 patients) resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%).

Conclusions: Investigation using stringent MRI criteria and ultrasound-guided biopsy could accurately predict patients with pCR after NAC. A larger prospective clinical trial evaluating the clinical safety of breast surgery omission after NAC in selected patients will be conducted based on these findings.
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http://dx.doi.org/10.1007/s10549-020-05678-3DOI Listing
July 2020

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

J Breast Cancer 2020 Apr 20;23(2):182-193. Epub 2020 Apr 20.

Cancer Research Institute, Seoul National University, Seoul, Korea.

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; = 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.
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http://dx.doi.org/10.4048/jbc.2020.23.e28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192742PMC
April 2020

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

J Breast Cancer 2020 Apr 9;23(2):162-170. Epub 2020 Mar 9.

Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

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 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 . 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.
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http://dx.doi.org/10.4048/jbc.2020.23.e20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192749PMC
April 2020

NAD(P)-dependent steroid dehydrogenase-like is involved in breast cancer cell growth and metastasis.

BMC Cancer 2020 May 4;20(1):375. Epub 2020 May 4.

Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: The cholesterol biosynthesis pathway is typically upregulated in breast cancer. The role of NAD(P)-dependent steroid dehydrogenase-like (NSDHL) gene, which is involved in cholesterol biosynthesis, in breast cancer remains unknown. This study aimed to uncover the role of NSDHL in the growth and metastasis of breast cancer.

Methods: After NSDHL knockdown by transfection of short interfering RNA into human breast cancer cell lines (MCF-7, MDA-MB-231 and BT-20) and human breast epithelial cell line (MCF10A), cell proliferation assay, cell cycle analysis, three-dimensional cell culture, clonogenic assay, transwell migration and invasion assays, and wound healing assay were performed. Erlotinib was used as the target drug for epidermal growth factor receptor. Immunodeficient mice (NOD.Cg-Prkdcscid Il2rgtm1wjl /SzJ) were used as orthotropic breast tumor models by injecting them with NSDHL-knockdown MDA-MB-231 cells using lentivirus-carrying NSDHL short hairpin RNA. Clinical data from 3951 breast cancer patients in Gene Expression Omnibus databases were used to investigate the potential prognostic role of NSDHL by survival analysis.

Results: NSDHL knockdown in BT-20, and MDA-MB-231 resulted in a significant decrease in their viability, colony formation, migration, and invasion abilities (p < 0.05). Total cholesterol levels were observed to be significantly decreased in NSDHL-knockdown BT-20 and MDA-MB-231 (p < 0.0001). NSDHL knockdown significantly increased the rate of erlotinib-induced cell death, especially in MDA-MB-231 (p = 0.01). NSDHL knockdown led to significantly decreased tumor growth and lung metastasis in the MDA-MB-231 xenograft model (p < 0.01). Clinically, high NSDHL expression in tumors of patients with breast cancer was associated with significantly reduced recurrence-free survival (p < 0.0001).

Conclusions: NSDHL might have a role in promoting breast cancer progression. The usage of NSDHL as a therapeutic target in breast cancer needs to be clarified in further studies.
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http://dx.doi.org/10.1186/s12885-020-06840-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197182PMC
May 2020

Efficacy of health coaching and a web-based program on physical activity, weight, and distress management among cancer survivors: A multi-centered randomised controlled trial.

Psychooncology 2020 07 23;29(7):1105-1114. Epub 2020 Apr 23.

Department of Family Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Objectives: To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients.

Methods: This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months.

Results: Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P < .001) than the control group, but not in PA and weight.

Conclusion: The web-based program, with or without health coaching, may improve health behaviours including PA, weight, and distress management among cancer survivors within 2 months of completing primary cancer treatment. The web-based program with health coaching was mainly effective for reducing psychological distress.
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http://dx.doi.org/10.1002/pon.5394DOI Listing
July 2020

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

J Breast Cancer 2020 02 3;23(1):113-114. Epub 2020 Jan 3.

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

[This corrects the article on p. 579 in vol. 22, PMID: 31897331.].
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http://dx.doi.org/10.4048/jbc.2020.23.e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043948PMC
February 2020

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants.

Nat Commun 2020 03 5;11(1):1217. Epub 2020 Mar 5.

Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
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http://dx.doi.org/10.1038/s41467-020-15046-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057957PMC
March 2020

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test.

Cancer Res Treat 2020 Jul 4;52(3):697-713. Epub 2020 Feb 4.

Department of Surgery, Seoul National University Hospital, Seoul, Korea.

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 next-generation 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.
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http://dx.doi.org/10.4143/crt.2019.559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373875PMC
July 2020

Oncologic outcomes after immediate breast reconstruction following mastectomy: comparison of implant and flap using propensity score matching.

BMC Cancer 2020 Jan 30;20(1):78. Epub 2020 Jan 30.

Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul, South Korea.

Background: Although immediate breast reconstruction has been reported to be oncologically safe, no affirmative study comparing the two reconstruction methods exists. We investigated breast cancer recurrence rates in two breast reconstruction types; implant reconstruction and autologous flap reconstruction.

Methods: A retrospective cohort study was performed on propensity score-matched (for age, stage, estrogen receptor status) patients who underwent IBR after mastectomy at Seoul National University Hospital between 2010 and 2014. The main outcomes determined were locoregional recurrence-free interval (LRRFI) and disease-free interval (DFI).

Results: We analyzed 496 patients among 731 patients following propensity score matching (Median age 43, 247 implant reconstruction and 249 flap reconstruction). During median follow-up of 58.2 months, DFI was not different between the two groups at each tumor stage. However, flap reconstruction showed inferior DFI compared to implant reconstruction in patients with high histologic grade (p = 0.012), and with high Ki-67 (p = 0.028). Flap reconstruction was related to short DFI in multivariate analysis in aggressive tumor subsets. Short DFI after flap reconstruction in aggressive tumor cell phenotype was most evident in hormone positive/Her-2 negative cancer (p = 0.008). LRRFI, on the other hand, did not show difference according to reconstruction method regardless of tumor cell aggressiveness.

Conclusion: Although there is no difference in cancer recurrence according to reconstruction method in general, flap-based reconstruction showed higher systemic recurrence associated with histologically aggressive tumors.
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http://dx.doi.org/10.1186/s12885-020-6568-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993337PMC
January 2020

Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer.

J Oncol 2019 28;2019:7386734. Epub 2019 Dec 28.

Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer.

Methods: The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery.

Results: A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) ( < 0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them ( < 0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50-6.19; =0.002).

Conclusions: Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.
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http://dx.doi.org/10.1155/2019/7386734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949686PMC
December 2019

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

J Breast Cancer 2019 Dec 10;22(4):579-586. Epub 2019 Dec 10.

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

Purpose: Currently, the standard screening tool for breast cancer is screening mammography. There have been many efforts to develop a blood-based diagnostic assay for breast cancer diagnosis; however, none have been approved for clinical use at this time. The purpose of this study was to determine the accuracy of a novel blood-based proteomic test for aiding breast cancer diagnosis in a relatively large cohort of cancer patients.

Methods: A blood-based test using multiple reaction monitoring (MRM) measured by mass spectrometry to quantify 3 peptides (apolipoprotein C-1, carbonic anhydrase 1, and neural cell adhesion molecule L1-like protein) present in human plasma was investigated. A total of 1,129 blood samples from 575 breast cancer patients, 454 healthy controls, and 100 patients with other malignancies were used to verify and optimize the assay.

Results: The diagnostic sensitivity, specificity, and accuracy of the MRM-based proteomic assay were 71.6%, 85.3%, and 77%, respectively; the area under the receiver operating characteristic curve was 0.8323. The proteomic assay did not demonstrate diagnostic accuracy in patients with other types of malignancies including thyroid, pancreatic, lung, and colon cancers. The diagnostic performance of the proteomic assay was not associated with the timing of blood sampling before or after anesthesia.

Conclusion: The data demonstrated that an MRM-based proteomic assay that measures plasma levels of three specific peptides can be a useful tool for breast cancer screening and its accuracy is cancer-type specific.
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http://dx.doi.org/10.4048/jbc.2019.22.e57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933034PMC
December 2019

Profiles of depressive symptoms and the association with anxiety and quality of life in breast cancer survivors: a latent profile analysis.

Qual Life Res 2020 Feb 18;29(2):421-429. Epub 2019 Oct 18.

Department of Food and Nutrition, Seoul National University, Seoul, Korea.

Purpose: The aim of this study was to examine profiles of depressive symptoms and the association with anxiety and quality of life (QOL) in breast cancer survivors.

Methods: A cross-sectional multicenter survey involving 5 hospitals in Korea was implemented between February 2015 and January 2017. A self-report survey included the Patient Health Questionnaire-9, Short Form 36, and State and Trait Anxiety Scale. Data from 347 patients were analyzed.

Results: Latent profile analysis identified five profiles of depressive symptoms: (1) "no depression" (63.98%); (2) "mild depression with sleep problems" (16.43%); (3) "mild depression" (8.65%); (4) "moderate depression with anhedonia" (7.78%); and (5) "moderately severe depression" (3.17%). Results from Fisher's exact test and analysis of variance (ANOVA) to examine whether sociodemographic and clinical characteristics distinguish the classes indicated that marital status, income and education as well as C-reactive protein distinguished a few classes. Multivariate analysis of covariance and analysis of covariance results indicated that both types of anxiety as well as several dimensions of QOL differed between the identified classes.

Conclusions: The current results suggest that although identified classes were characterized overall by severity of depression, a few classes also reflected pronounced individual symptom patterns, warranting tailored interventions for these symptom patterns, along with overall severity of depression.
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http://dx.doi.org/10.1007/s11136-019-02330-6DOI Listing
February 2020
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