Relationship Between Breast and Axillary Pathologic Complete Response According to Clinical Nodal Stage: A Nationwide Study From Korean Breast Cancer Society / 한국유방암학회지

Purpose@#We evaluated the relationship between breast pathologic complete response (BpCR) and axillary pathologic complete response (ApCR) after neoadjuvant chemotherapy (NACT) according to nodal burden at presentation. As the indications for NACT have expanded, clinicians have started clinical trials for the omission of surgery from the treatment plan in patients with excellent responses to NACT. However, the appropriate indications for axillary surgery omission after excellent NACT response remain unclear. @*Methods@#Data were collected from patients in the Korean Breast Cancer Society Registry who underwent NACT followed by surgery between 2010 and 2020. We analyzed pathologic axillary nodal positivity after NACT according to BpCR stratified by tumor subtype in patients with cT1-3/N0-2 disease at diagnosis. @*Results@#A total of 6,597 patients were identified. Regarding cT stage, 528 (9.5%), 3,778 (67.8%), and 1,268 (22.7%) patients had cT1, cT2, and cT3 disease, respectively. Regarding cN stage, 1,539 (27.7%), 2,976 (53.6%), and 1,036 (18.7%) patients had cN0, cN1, and cN2 disease, respectively. BpCR occurred in 21.6% (n = 1,427) of patients, while ApCR and pathologic complete response (ypCR) occurred in 59.7% (n = 3,929) and ypCR 19.4% (n = 1,285) of patients, respectively. The distribution of biologic subtypes included 2,329 (39.3%) patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease, 1,122 (18.9%) with HR-positive/HER2-positive disease, 405 (6.8%) with HR-negative/HER2-positive disease, and 2,072 (35.0%) with triple-negative breast cancer . Among the patients with BpCR, 89.6% (1,122/1,252) had ApCR. Of those with cN0 disease, most (99.0%, 301/304) showed ApCR. Among patients with cN1-2 disease, 86.6% (821/948) had ApCR. @*Conclusion@#BpCR was highly correlated with ApCR after NACT. In patients with cN0 and BpCR, the risk of missing axillary nodal metastasis was low after NACT. Further research on axillary surgery omission in patients with cN0 disease is needed.

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.

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.

Nomogram for accurate prediction of breast and axillary pathologic response after neoadjuvant chemotherapy in node positive patients with breast cancer

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.

Oncologic Outcomes of Nipple-Sparing Mastectomy with Immediate Breast Reconstruction in Patients with Tumor–Nipple Distance Less than 2.0 cm / 한국유방암학회지

Use of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Patients with Axillary Node-Positive Breast Cancer in Diagnosis / 한국유방암학회지

PURPOSE: This study aimed to evaluate the effects of sentinel lymph node biopsy (SLNB) on recurrence and survival after neoadjuvant chemotherapy (NAC) in breast cancer patients with cytology-proven axillary node metastasis. METHODS: We selected patients who were diagnosed with invasive breast cancer and axillary lymph node metastasis and were treated with NAC followed by curative surgery between January 2007 and December 2014. We classified patients into three groups: group A, negative sentinel lymph node (SLN) status and no further dissection; group B, negative SLN status with backup axillary lymph node dissection (ALND); and group C, no residual axillary metastasis on pathology with standard ALND. RESULTS: The median follow-up time was 51 months (range, 3–122 months) and the median number of retrieved SLNs was 5 (range, 2–9). The SLN identification rate was 98.3% (234/238 patients), and the false negative rate of SLNB after NAC was 7.5%. There was no significant difference in axillary recurrence-free survival (p=0.118), disease-free survival (DFS; p=0.578) or overall survival (OS; p=0.149) among groups A, B, and C. In the subgroup analysis of breast pathologic complete response (pCR) status, there was no significant difference in DFS (p=0.271, p=0.892) or OS (p=0.207, p=0.300) in the breast pCR and non-pCR patients. CONCLUSION: These results suggest that SLNB can be feasible and oncologically safe after NAC for cytology-determined axillary node metastasis patients and could help reduce arm morbidity and lymphedema by avoiding ALND in SLN-negative patients.

Patterns of Axillary Lymph Node Metastasis in Breast Cancer: A Prospective Single-Center Study / 한국유방암학회지

PURPOSE: The recent trend in breast cancer treatment is to minimize axillary dissection. However, no pattern of axillary metastasis has been precisely established. The purpose of this study was to evaluate the metastatic lymphatic pattern using near-infrared fluorescence imaging with indocyanine green (ICG) in breast cancer with cytologically proven axillary metastasis. METHODS: This was a prospective single-center study. We evaluated 147 patients with breast cancer involving cytologically proven axillary metastasis, and compared physiological and nonphysiological lymphatic metastasis. RESULTS: We performed lymphatic mapping for 64 patients who exhibited level II lymphatic flow on near-infrared fluorescence imaging with ICG, and found that all had axillary metastasis: 51 patients who did not receive neoadjuvant chemotherapy (NAC) and 13 patients post-NAC. Of patients who did not receive NAC, 32 had physiological lymphatic metastasis and 19 had nonphysiological lymphatic metastasis. The risk factors for nonphysiological lymphatic metastasis were age ≥55 years, high Ki-67 index (>20%), and perinodal extension in both univariate and multivariate analysis (p < 0.05). CONCLUSION: Patients with identified risk factors in cytologically-proven axillary metastasis who did not receive NAC may have nonphysiological lymphatic metastasis.

Erratum: Development of a Nomogram to Predict N2 or N3 Stage in T1-2 Invasive Breast Cancer Patients with No Palpable Lymphadenopathy / 한국유방암학회지

This article was initially published on the Journal of Breast Cancer with a misspelled the name of third author.

Necessity of In Situ Hybridization Test of Human Epidermal Growth Factor Receptor 2 (HER2) Status in Breast Cancer Patients with Equivocal HER2 Immunohistochemistry Results

PURPOSE: Accurate human epidermal growth factor receptor 2 (HER2) status is important in predicting prognosis and providing treatment for HER2-positive breast cancer patients. However, performing in situ hybridization (ISH) can be an economic burden on developing countries. This study aimed to find an alternative to the ISH test by predicting the HER2 status in patients with equivocal immunohistochemistry (IHC) results. METHODS: We retrospectively reviewed the clinical data of 15,535 patients who underwent curative surgery for invasive breast cancer between February 2005 and April 2015 at the Samsung Medical Center. Equivocal HER2 IHC results were obtained for 461 patients. Logistic regression analysis using stepwise selection was performed to identify the clinicopathological factors related to silver in situ hybridization (SISH) status. We analyzed the data by dividing the estrogen receptor and progesterone receptor (PR) into three groups according to Allred score. RESULTS: Multivariable analysis identified poorly differentiated histological grade, lower PR score, higher expression of Ki-67 and p53, and lower expression of cytokeratin 5/6 and epidermal growth factor receptor as predictors of SISH-positive results. The area under the curve for the receiver-operating characteristic curve was 0.74. CONCLUSION: We identified factors related to a positive HER2 status by SISH. However, there was insufficient power in the prediction model for diagnosis and evaluation. Therefore, the SISH test is essential in determining the HER2 status of breast cancer patients when the IHC result is equivocal.

Prognostic Validation of the American Joint Committee on Cancer 8th Staging System in 24,014 Korean Patients with Breast Cancer / 한국유방암학회지

PURPOSE: The American Joint Committee on Cancer (AJCC) recently released the breast cancer staging system, 8th edition, which included additional four biologic factors. However, there has been no external validation of the prognostic value of the new stages with different population-based databases. METHODS: To validate the prognostic value of the new staging system in the Asian population, with a focus on Korean patients with breast cancer, we performed a retrospective study with data from the Korean Breast Cancer Society that included 24,014 patients with invasive ductal or lobular carcinoma who underwent surgery between January 2009 and January 2012 in Korea. The proportional differences were evaluated between the anatomic staging system (AJCC 7th edition) and the prognostic staging system (AJCC 8th edition, December 2017 published version). Comparisons of overall survival (OS) and disease-free survival (DFS) with Kaplan-Meier graphs and hazard ratios were also performed. RESULTS: Our analysis included 24,014 patients (median age, 50 years; range, 20–91 years). Stage I, II, and III disease accounted for 47.6%, 43.5%, and 8.9%, respectively, of anatomic stages and 61.8%, 27.6%, and 10.8%, respectively, of clinical prognostic stages. A total of 6,272 cases (26.1%) were upstaged, 4,656 (19.4%) were downstaged, and 13,086 (54.5%) remained unchanged. OS and DFS decreased in the order from prognostic stages IA to IIIC but did not change among the anatomic stage groups. CONCLUSION: Our data suggests that the prognostic staging system provides superior prognostic value to the anatomic staging system in Korean patients with breast cancer.

Verification of a Western Nomogram for Predicting Oncotype DX™ Recurrence Scores in Korean Patients with Breast Cancer / 한국유방암학회지

A recent study conducted at the University of Tennessee Medical Center using a large dataset from the National Cancer Database (NCDB) reported the use of nomograms for predicting Oncotype DX™ (ODX) scores with clinicopathologic data. We reviewed the data of 218 patients who underwent the ODX test at a single institution in Korea to confirm that nomograms can accurately predict ODX score groups using our data, which differ from those of the NCDB in terms of ethnicity. The concordance index (c-index) of nomograms was much lower than that of the University of Tennessee Medical Center for high- and low-risk groups of commercial ODX and Trial Assigning Individualized Options for Treatment values. Although the nomogram for predicting ODX scores was based on a large dataset, it could not be generalized to patients in Asia. Further studies using large datasets of patients from different ethnicities should be performed to develop a nomogram applicable to patients worldwide.

Development of a Nomogram to Predict N2 or N3 Stage in T1–2 Invasive Breast Cancer Patients with No Palpable Lymphadenopathy / 한국유방암학회지

PURPOSE: Subsequent to the American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trials, complete axillary lymph node dissection is not routinely performed, even in cases where metastatic sentinel lymph nodes are detected. We investigated the percentage of N2 or N3 stages in T1–2 invasive breast cancer patients with no lymphadenopathy and developed a nomogram to predict the possibility of N2 or N3 stages in these patients. METHODS: We retrospectively reviewed the charts of invasive breast cancer patients who were clinically N0 stage, but had a positive sentinel or non-sentinel lymph node detected on sentinel lymph node biopsy. The association of potential risk factors with known outcomes (N2 or N3 stages) was tested using logistic regression analysis. Variables with p<0.05 in the multivariate analysis were included in the nomogram. Internal performance validation was carried out using a 5-fold cross validation method. RESULTS: Among a total of 1,437 patients, 1,355 patients had stage N1 disease (94.3%), while 82 had stage N2 or N3 disease (5.7%). Multivariate stepwise logistic regression analysis revealed lymphovascular invasion (p=0.008), T2 stage (p=0.026), metastatic lymph node ratio (p<0.001), and perinodal extension (p<0.001) as independent predictors of N2 or N3 stages. A nomogram was developed based on these factors. The area under the curve estimated from the receiver operating characteristic graph was 0.8050 in the model set and 0.8246 in the test set. CONCLUSION: Our nomogram can be employed for the prediction of N2 or N3 stage among cases fulfilling the ACOSOG Z0011 or AMAROS criteria.

Risk Factors and Tumor Recurrence in pT1N0M0 Gastric Cancer after Surgical Treatment

PURPOSE: This study aimed to evaluate the rate, patterns, and risk factors associated with tumor recurrence in patients with T1N0 gastric cancer. MATERIALS AND METHODS: The medical records of 8,753 patients with pathological T1N0M0 gastric cancer who underwent gastrectomy between 1994 and 2014 at Sungkyunkwan University School of Medicine were examined. RESULTS: Among the 8,753 patients, 95 patients (1.1%) experienced tumor recurrence; this included 31 remnant, 27 hematogenous, 9 lymph nodal, 5 peritoneal, and 23 multiple-site recurrences. When patients were divided into two groups according to the presence of tumor recurrence, the following characteristics were higher in the recurrence group than in the non-recurrence group: older age (≥65 years), male gender, undifferentiated histology, submucosal invasion, and venous invasion. In multivariate analysis, older age, male gender, tumor depth (sm2 and sm3 invasion), and venous invasion were independent risk factors for tumor recurrence. The recurrence rates were 0.7% in patients with less than two risk factors, 1.7% in those with two risk factors, 3.0% in those with three risk factors, and 6.3% in those with four risk factors (P<0.001). CONCLUSIONS: Although tumor recurrence is rare in pT1N0M0 gastric cancer, some patients with certain risk factors demonstrate an increased rate of tumor recurrence. Careful follow-up is required for patients with three or four risk factors.

Nutrition Teachers' Perception of the Importance and Performance Frequency of Their Roles in the Indicators and Items on a Teacher Evaluation

This study was conducted to determine the appropriateness of the indicators and items on teacher evaluations for professional development and to provide insight for their improvement. To accomplish this, the perception of the importance and performance frequency of 318 nutrition teachers regarding their roles inherent in the indicators and items were evaluated through a survey questionnaire based on a five-point Likert scale. The quantitative data were analyzed using descriptive statistics and a paired t-test. In addition, the reflective analysis and constant comparison method were employed to analyze the responses to the open-ended questions asking problems in the indicators and items. The results revealed that the mean scores for the importance and performance frequency of most indicators and items were over four points, which implies that most indicators and items are appropriate for evaluating the job tasks of nutrition teachers. However, it was suggested that a few items be revised or removed for their improvement and appropriateness. This study concluded that nutrition teachers should have more chances to provide nutrition education for students to enable them to perform as teachers and not simply dietitians.