Comparative profiling by data-independent acquisition mass spectrometry reveals featured plasma proteins in breast cancer: a pilot study

Purpose@#Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers. @*Methods@#This pilot study was conducted using bioresources from Seoul National University Bundang Hospital’s Human Bioresource Center. Serum samples from 10 breast cancer patients and 10 healthy controls were obtained. Liquid chromatography-mass spectrometry analysis was performed to identify differentially expressed proteins. @*Results@#We identified 891 proteins; 805 were expressed in the breast cancer group and 882 in the control group. Gene set enrichment and differential expression analysis identified 30 upregulated and 100 downregulated proteins in breast cancer. Among these, 10 proteins were selected as potential biomarkers. Three proteins were upregulated in breast cancer patients, including cluster of differentiation 44, eukaryotic translation initiation factor 2-α kinase 3, and fibronectin 1. Seven proteins downregulated in breast cancer patients were also selected: glyceraldehyde-3-phosphate dehydrogenase, α-enolase, heat shock protein member 8, integrin‑linked kinase, tissue inhibitor of metalloproteinases-1, vasodilatorstimulated phosphoprotein, and 14-3-3 protein gamma. All proteins had been previously reported to be related to tumor development and progression. @*Conclusion@#The findings suggest that plasma proteome profiling can reveal potential diagnostic biomarkers for breast cancer and may contribute to early detection and personalized treatment strategies. A further validation study with a larger sample cohort of breast cancer patients is planned.

Automated Versus Handheld Breast Ultrasound for Evaluating Axillary Lymph Nodes in Patients With Breast Cancer

Objective@#Automated breast ultrasound (ABUS) is a relevant imaging technique for early breast cancer diagnosis and is increasingly being used as a supplementary tool for mammography. This study compared the performance of ABUS and handheld ultrasound (HHUS) in detecting and characterizing the axillary lymph nodes (LNs) in patients with breast cancer. @*Materials and Methods@#We retrospectively reviewed the medical records of women with recently diagnosed early breast cancer (≤ T2) who underwent both ABUS and HHUS examinations for axilla (September 2017–May 2018). ABUS and HHUS findings were compared using pathological outcomes as reference standards. Diagnostic performance in predicting any axillary LN metastasis and heavy nodal-burden metastases (i.e., ≥ 3 LNs) was evaluated. The ABUS-HHUS agreement for visibility and US findings was calculated. @*Results@#The study included 377 women (53.1 ± 11.1 years). Among 385 breast cancers in 377 patients, 101 had axillary LN metastases and 30 had heavy nodal burden metastases. ABUS identified benign-looking or suspicious axillary LNs (average, 1.4 ± 0.8) in 246 axillae (63.9%, 246/385). According to the per-breast analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of ABUS in predicting axillary LN metastases were 43.6% (44/101), 95.1% (270/284), 75.9% (44/58), 82.6% (270/327), and 81.6% (314/385), respectively. The corresponding results for HHUS were 41.6% (42/101), 95.1% (270/284), 75.0% (42/56), 82.1% (270/329), and 81.0% (312/385), respectively, which were not significantly different from those of ABUS (P ≥ 0.53). The performance results for heavy nodal-burden metastases were 70.0% (21/30), 89.6% (318/355), 36.2% (21/58), 97.3% (318/327), and 88.1% (339/385), respectively, for ABUS and 66.7% (20/30), 89.9% (319/355), 35.7% (20/56), 97.0% (319/329), and 88.1% (339/385), respectively, for HHUS, also not showing significant difference (P ≥ 0.57). The ABUS–HHUS agreement was 95.9% (236/246; Cohen’s kappa = 0.883). @*Conclusion@#Although ABUS showed limited sensitivity in diagnosing axillary LN metastasis in early breast cancer, it was still useful as the performance was comparable to that of HHUS.

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.

Development and External Validation of a Machine Learning Model to Predict Pathological Complete Response After Neoadjuvant Chemotherapy in Breast Cancer / 한국유방암학회지

Purpose@#Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. @*Methods@#The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. @*Results@#A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). @*Conclusion@#Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

The Value of Adding Ductography to Ultrasonography for the Evaluation of Pathologic Nipple Discharge in Women with Negative Mammography

Objective@#The optimal imaging approach for evaluating pathological nipple discharge remains unclear. We investigated the value of adding ductography to ultrasound (US) for evaluating pathologic nipple discharge in patients with negative mammography findings. @*Materials and Methods@#From July 2003 to December 2018, 101 women (mean age, 46.3 ± 12.2 years; range, 23–75 years) with pathologic nipple discharge were evaluated using pre-ductography (initial) US, ductography, and post-ductography US. The imaging findings were reviewed retrospectively. The standard reference was surgery (70 patients) or > 2 years of followup with US (31 patients). The diagnostic performances of initial US, ductography, and post-ductography US for detecting malignancy were compared using the McNemar’s test or a generalized estimating equation. @*Results@#In total, 47 papillomas, 30 other benign lesions, seven high-risk lesions, and 17 malignant lesions were identified as underlying causes of pathologic nipple discharge. Only eight of the 17 malignancies were detected on the initial US, while the remaining nine malignancies were detected by ductography. Among the nine malignancies detected by ductography, eight were detected on post-ductography US and could be localized for US-guided intervention. The sensitivities of ductography (94.1% [16/17]) and post-ductography US (94.1% [16/17]) were significantly higher than those of initial US (47.1% [8/17]; p = 0.027 and 0.013, respectively). The negative predictive value of post-ductography US (96.9% [31/32]) was significantly higher than that of the initial US (83.3% [45/54]; p = 0.006). Specificity was significantly higher for initial US than for ductography and post-ductography US (p = 0.001 for all). @*Conclusion@#The combined use of ductography and US has a high sensitivity for detecting malignancy in patients with pathologic nipple discharge and negative mammography. Ductography findings enable lesion localization on second-look post-ductography US, thus facilitating the selection of optimal treatment plans.

Effect of Poloxamer-Based ThermoSensitive Sol-Gel Agent on Upper Limb Dysfunction after Axillary Lymph Node Dissection: A Double-Blind Randomized Clinical Trial / 한국유방암학회지

Purpose@#Restricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer.This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND. @*Methods@#We designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period). @*Results@#A total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (−30.04 ± 27.76 vs. −42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (−3.92 ± 9.80 vs. −10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group. @*Conclusion@#We suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND.

Aesthetic Scar-Less Mastectomy and Breast Reconstruction / 한국유방암학회지

Surgical approaches in breast cancer have been changing to ensure both oncologic safety and cosmetic results. Although the concept of “oncoplastic breast surgery” has been accepted for decades, breast and plastic surgeons have been striving to develop more advanced surgical skills that ensure non-inferior oncologic outcomes with better cosmetic outcomes.Endoscopic or robotic devices, which are currently available only for chest or abdominal surgeries, could be used for breast surgery to ensure better cosmetic outcomes. The authors refer to this surgical concept as “aesthetic scar-less breast surgery and reconstruction,” a term that encompasses the consequential concepts rather than naming it with simple technical words such as endoscopy-assisted or robot-assisted surgery. The “scar-less” term simply means leaving less of a scar, and better results can be expected by designing incisions on invisible areas. Herein, we summarize our experiences with various techniques of “aesthetic scar-less” surgery and review the existing literature on this topic.

Effect of Poloxamer-Based ThermoSensitive Sol-Gel Agent on Upper Limb Dysfunction after Axillary Lymph Node Dissection: A Double-Blind Randomized Clinical Trial / 한국유방암학회지

Purpose@#Restricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer.This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND. @*Methods@#We designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period). @*Results@#A total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (−30.04 ± 27.76 vs. −42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (−3.92 ± 9.80 vs. −10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group. @*Conclusion@#We suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND.

Aesthetic Scar-Less Mastectomy and Breast Reconstruction / 한국유방암학회지

Surgical approaches in breast cancer have been changing to ensure both oncologic safety and cosmetic results. Although the concept of “oncoplastic breast surgery” has been accepted for decades, breast and plastic surgeons have been striving to develop more advanced surgical skills that ensure non-inferior oncologic outcomes with better cosmetic outcomes.Endoscopic or robotic devices, which are currently available only for chest or abdominal surgeries, could be used for breast surgery to ensure better cosmetic outcomes. The authors refer to this surgical concept as “aesthetic scar-less breast surgery and reconstruction,” a term that encompasses the consequential concepts rather than naming it with simple technical words such as endoscopy-assisted or robot-assisted surgery. The “scar-less” term simply means leaving less of a scar, and better results can be expected by designing incisions on invisible areas. Herein, we summarize our experiences with various techniques of “aesthetic scar-less” surgery and review the existing literature on this topic.

Ultrasonography and ultrasound-guided fine-needle aspiration biopsy can predict a heavy nodal metastatic burden in early-stage breast cancer

Purpose@#This study aimed to predict a heavy nodal burden (≥3 metastatic axillary lymph nodes [LNs]) using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) in patients with early-stage breast cancer. @*Methods@#We retrospectively reviewed the medical records of 403 women (404 cancers) who underwent US-guided FNAB for axillary LN staging from January 2006 to December 2015. US findings and US-guided FNAB results were reviewed and compared using pathology results as the reference. Diagnostic performance was analyzed, and clinicopathological and radiological findings were compared between patients with <3 metastatic LNs and ≥3 metastatic LNs. @*Results@#The final pathology results revealed that 20.5% of cancers had heavy nodal metastases. US-guided FNAB showed significantly higher sensitivity (79.0% vs. 63.0%, P=0.009) and specificity (84.8% vs. 79.3%, P=0.036) in predicting heavy nodal metastases than did US. The presence of a larger number of suspicious LNs (two or more) on axillary US and positive FNAB results were significantly correlated with a heavy nodal burden in the multivariate analysis. The odds ratios were 4.20 (95% confidence interval [CI], 1.90 to 9.39) for two suspicious LNs, 9.40 (95% CI, 2.99 to 29.54) for three or more suspicious LNs, and 14.22 (95% CI, 6.78 to 29.82) for positive FNAB results. @*Conclusion@#The number of suspicious LNs detected on axillary US and FNAB results can help predict a heavy axillary nodal burden in patients with early-stage breast cancer.

Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients

BRCA1/2 germline mutations account for the majority of hereditary breast cancers. Since the identification of the BRCA genes, several attempts have been made to define the clinicopathological characteristics of BRCA-associated breast cancer in comparison with sporadic breast cancer. Asians constitute 60% of the world population, and although the incidence of breast cancer in Asia remains low compared to the West, breast cancer is the most prevalent female cancer in the region. The epidemiological aspects of breast cancer are different between Asians and Caucasians. Asian patients present with breast cancer at a younger age than Western patients. The contributions of BRCA1/2 mutations to breast cancer incidence are expected to differ between Asians and Caucasians, and the different genetic backgrounds among races are likely to influence the breast cancer phenotypes. However, most large-scale studies on the clinicopathological characteristics of BRCA-associated breast cancer have been on Western patients, while studies on Asian populations were small and sporadic. In this review, we provide an overview of the clinical and pathological characteristics of BRCA-associated breast cancer, incorporating findings on Asian patients.

Treatment Patterns and Clinical Outcomes in Elderly Patients with Breast Cancer

Purpose@#Although the number of elderly patients with breast cancer is increasing as the population ages, their treatment is controversial. We evaluated the prognostic factors associated with survival in elderly breast cancer patients and assessed the impact of comorbidity on prognosis. @*Methods@#This study included 362 patients (aged ≥65 years) who underwent surgery for breast cancer in our institution between 2003 and 2014. The patients were divided into early-aged (65–74 years) and late-aged (≥75 years) groups. Comorbidity was parametrized using the Charlson comorbidity index (CCI). Kaplan–Meier analysis was used to analyze overall survival (OS) and distant metastasis-free survival (DMFS). Prognostic factors were evaluated by Cox proportional hazards regression. @*Results@#The surgical method, subtypes, stage, and oncological features were similar between early- and late-aged groups; however, smaller proportions of patients in the late-aged group received chemotherapy (12.9% vs. 45.5%) and endocrine therapy (55.3% vs. 73.3%). In multivariable analysis, the poor prognostic factors associated with DMFS and OS were high CCI, high histologic grade, and advanced stage. Chemotherapy, endocrine therapy, and radiotherapy were not significantly related to DMFS and OS. @*Conclusion@#In this study, adjuvant treatments did not affect the prognosis of elderly patients with breast cancer. To clarify the effects of adjuvant therapies in these patients, a large-scale retrospective study that considers not only tumor characteristics but also life expectancy is necessary.

Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. @*Materials and Methods@#The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. @*Results@#The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. @*Conclusion@#L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

Implementation of a resident night float system in a surgery department in Korea for 6 months: electronic medical record-based big data analysis and medical staff survey

PURPOSE: To evaluate superiority of a night float (NF) system in comparison to a traditional night on-call (NO) system for surgical residents at a single institution in terms of efficacy, safety, and satisfaction. METHODS: A NF system was implemented from March to September 2017 and big data analysis from electronic medical records was performed for all patients admitted for surgery or contacted from the emergency room (ER). Parameters including vital signs, mortality, and morbidity rates, as well as promptness of response to ER calls, were compared against a comparable period (March to September 2016) during which a NO system was in effect. A survey was also performed for physicians and nurses who had experienced both systems. RESULTS: A total of 150,000 clinical data were analyzed. Under the NO and NF systems, a total of 3,900 and 3,726 patients were admitted for surgery. Mortality rates were similar but postoperative bleeding was significantly higher in the NO system (0.5% vs. 0.2%, P = 0.031). From the 1,462 and 1,354 patients under the NO and NF systems respectively, that required surgical consultation from the ER, the time to response was significantly shorter in the NF system (54.5 ± 70.7 minutes vs. 66.8 ± 83.8 minutes, P < 0.001). Both physicians (90.4%) and nurses (91.4%) agreed that the NF system was more beneficial. CONCLUSION: This is the first report of a NF system using big data analysis in Korea, and potential benefits of this new system were observed in both ward and ER patient management.

Changes in Biomarker Status in Metastatic Breast Cancer and Their Prognostic Value / 한국유방암학회지

PURPOSE: There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis. METHODS: A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer. CONCLUSION: Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.

Contralateral Breast Cancer and Ipsilateral Breast Tumor Recurrence in BRCA1/2 Carriers and Non-Carriers at High-Risk of Hereditary Breast Cancer / 한국유방암학회지

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST. MATERIALS AND METHODS: The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup. CONCLUSION: ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

A Novel Prognostic Nomogram for Predicting Risks of Distant Failure in Patients with Invasive Breast Cancer Following Postoperative Adjuvant Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer. MATERIALS AND METHODS: A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model. RESULTS: The 7-year overall survival and 5-year post-progression survival of locoregional versus distant recurrence groups were 67.6% versus 39.1% (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed distant metastasis showed early and late mortality risk peaks within 3 and after 5 years of follow-up, respectively, but a broad and low risk increment was observed in other patients with locoregional relapse. In multivariate analysis of distant metastasis-free interval, age (≥ 45 years vs. < 45 years), molecular subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3) were independently associated (p < 0.05 for all). Regarding the significant factors, a well-validated nomogram was established (concordance index, 0.812). The risk score level of patients with initial brain failure was higher than those of non-brain sites (p=0.029). CONCLUSION: The nomogram could be useful for predicting the individual probability of distant recurrence in breast cancer. In high-risk patients based on the risk scores, more aggressive systemic therapy and closer surveillance for metastatic failure should be considered.

Benign Intraductal Papilloma without Atypia on Core Needle Biopsy Has a Low Rate of Upgrading to Malignancy after Excision / 한국유방암학회지

PURPOSE: The management of benign intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial. This study was performed to evaluate the rate of upgrading to malignancy or high-risk lesions after excision and to identify factors associated with upgrading using a large series of benign IDP cases without atypia. METHODS: We included patients who were diagnosed as having benign IDP without atypia on CNB and underwent surgical or vacuum-assisted excision between 2010 and 2015. We analyzed the clinical, radiologic, and histopathologic features of IDPs that were upgraded to malignancy or high-risk lesions after excision. RESULTS: A total of 511 benign IDPs without atypia diagnosed via CNB were identified, of which 398 cases were treated with excision. After reviewing these cases, four cases of high-risk lesions in adjacent tissue on CNB, two cases which were revealed as papilloma with atypia, and nine cases of malignancy in the same breast were excluded. In the remaining 383 cases, the rate of upgrading to malignancy and high-risk lesions after excision was 0.8% and 4.4%, respectively. The presence of concurrent contralateral breast cancer, the presence of symptoms, and multifocality were factors significantly associated with upgrading to malignancy on subsequent excision. Surgical excision rather than vacuum-assisted excision was significantly associated with upgrading to high-risk lesions or malignancy. CONCLUSION: The rate of upgrading to malignancy for benign IDP without atypia was very low, suggesting that close clinical and radiologic observation may be sufficient for patients with benign IDP without atypia on CNB under proper settings.

Microinvasive Carcinoma versus Ductal Carcinoma In Situ: A Comparison of Clinicopathological Features and Clinical Outcomes / 한국유방암학회지

PURPOSE: Although microinvasive carcinoma is distinct from ductal carcinoma in situ (DCIS), the clinical significance of microinvasion in DCIS remains elusive. The purpose of this study is to evaluate the clinicopathological features and clinical outcomes of microinvasive carcinoma compared with pure DCIS. METHODS: We assessed 613 cases of DCIS and microinvasive carcinoma that were consecutively resected from 2003 to 2014 and analyzed clinicopathological variables, expression of standard biomarkers such as the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), p53, and Ki-67, and tumor recurrence. RESULTS: Among the 613 cases, 136 (22.2%) were classified as microinvasive carcinoma. Microinvasive carcinoma was significantly associated with DCIS with a large extent, high nuclear grade, necrosis, and comedotype architectural pattern. ER and PR expressions were dominantly observed in pure DCIS, whereas positive HER2 status, p53 overexpression, and high Ki-67 proliferation indices were more frequently observed in microinvasive carcinoma. Lymph node metastasis was found in only four cases of microinvasive carcinoma with multifocal microinvasion. In the multivariate analysis, DCIS with a large extent, comedo-type architectural pattern, and negative ER status were found to be independent predictors of microinvasion. During follow-up, 12 patients had ipsilateral breast recurrence, and no differences in recurrence rates were observed between patients with DCIS and those with microinvasive carcinoma. The triple-negative subtype was the only factor that was associated with tumor recurrence. CONCLUSION: Microinvasive carcinomas are distinct from DCIS in terms of clinicopathological features and biomarker expressions but are similar to DCIS in terms of clinical outcomes. Our results suggest that microinvasive carcinoma can be treated and followed up as pure DCIS.