Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor–Positive Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Clinicopathological Features and Prognosis of Lobular Carcinoma In Situ

Purpose@#According to the American Joint Committee on Cancer’s 8th Edition Manual, lobular carcinoma in situ (LCIS) is no longer considered a malignant disease, although it may be a precursor to the development of breast cancer. The present study aimed to evaluate the clinicopathological features and prognosis of LCIS. @*Methods@#This study retrospectively analyzed clinicopathological features and prognosis data of LCIS among patients who underwent breast surgery at Severance Hospital, Seoul, South Korea from 1991 to 2016. @*Results@#Of the 47 patients, 49 cases of LCIS were confirmed by postoperative pathology. The mean patient age was 48.15±8.34 years. Most patients (81.6%) did not have palpable tumors at diagnosis, and 51.0% showed no microcalcification on mammography. Breast-conserving surgery was performed more frequently than total mastectomy (77.6% vs. 22.4%). The mean tumor size was 1.63±2.11 cm. There were only 3 cases of pleomorphic LCIS. Hormone receptor-positive tumors were noted in 47 cases, however, the hormone receptor status was unknown in the other 2 cases. There were no LCIS recurrences or deaths during the follow-up period (mean 56 months). @*Conclusion@#LCIS is often incidentally diagnosed without clinical symptoms, especially in women aged <50 years. The prognosis of LCIS is excellent in cases that are surgically treated.

Comparison between Gasless and Gas-Inflated Robot-Assisted NippleSparing Mastectomy / 한국유방암학회지

Purpose@#Nipple-sparing mastectomy (NSM) includes various techniques, including conventional or endoscopic mastectomies. Since the introduction of robot-assisted NSM (RANSM) in 2015, 2 main methods have been used: gasless and gas-inflated techniques. The aim of this study was to compare clinicopathologic characteristics, surgical outcomes, and postoperative complications between patients treated with gasless RANSM and those treated with gas-inflated RANSM. @*Methods@#We conducted a retrospective study of women who underwent gasless or gasinflated RANSM with immediate breast reconstruction between November 2016 and May 2019. The indications for RANSM were early breast cancer, interstitial mastopathy, or BRCA1/2 mutation carriers. Clinicopathologic characteristics, surgical outcomes, and postoperative complications were analyzed. The severity of complications was graded using the Clavien-Dindo system. @*Results@#A total of 58 RANSM procedures were performed in 46 women: 15 cases of gasless RANSM and 43 cases of gas-inflated RANSM. The proportion of node-negative disease was higher in the gas-inflated group (97.1%) than in the gasless group (69.2%, p = 0.016).Adjuvant radiotherapy was administered in 30.6% of the cases in the gasless group and only 5% of the cases in the gas-inflated group. Other clinicopathological factors were not significantly different between the groups. Regarding surgical outcomes, the initial incision was 1 cm longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.20 ± 1.05 cm; p = 0.002). The final incision was also longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.57 ± 1.07 cm; p = 0.040). Operation time, complication rate, and complication grade were not significantly different between the 2 groups. @*Conclusion@#In this study, there were no significant differences in surgical outcomes or postoperative complications between gasless and gas-inflated RANSM, except for a longer incision with the gasless technique. Both techniques are reasonable options for RANSM followed by immediate reconstruction.

Clinicopathological Features and Prognosis of Lobular Carcinoma In Situ

Purpose@#According to the American Joint Committee on Cancer’s 8th Edition Manual, lobular carcinoma in situ (LCIS) is no longer considered a malignant disease, although it may be a precursor to the development of breast cancer. The present study aimed to evaluate the clinicopathological features and prognosis of LCIS. @*Methods@#This study retrospectively analyzed clinicopathological features and prognosis data of LCIS among patients who underwent breast surgery at Severance Hospital, Seoul, South Korea from 1991 to 2016. @*Results@#Of the 47 patients, 49 cases of LCIS were confirmed by postoperative pathology. The mean patient age was 48.15±8.34 years. Most patients (81.6%) did not have palpable tumors at diagnosis, and 51.0% showed no microcalcification on mammography. Breast-conserving surgery was performed more frequently than total mastectomy (77.6% vs. 22.4%). The mean tumor size was 1.63±2.11 cm. There were only 3 cases of pleomorphic LCIS. Hormone receptor-positive tumors were noted in 47 cases, however, the hormone receptor status was unknown in the other 2 cases. There were no LCIS recurrences or deaths during the follow-up period (mean 56 months). @*Conclusion@#LCIS is often incidentally diagnosed without clinical symptoms, especially in women aged <50 years. The prognosis of LCIS is excellent in cases that are surgically treated.

Comparison between Gasless and Gas-Inflated Robot-Assisted NippleSparing Mastectomy / 한국유방암학회지

Purpose@#Nipple-sparing mastectomy (NSM) includes various techniques, including conventional or endoscopic mastectomies. Since the introduction of robot-assisted NSM (RANSM) in 2015, 2 main methods have been used: gasless and gas-inflated techniques. The aim of this study was to compare clinicopathologic characteristics, surgical outcomes, and postoperative complications between patients treated with gasless RANSM and those treated with gas-inflated RANSM. @*Methods@#We conducted a retrospective study of women who underwent gasless or gasinflated RANSM with immediate breast reconstruction between November 2016 and May 2019. The indications for RANSM were early breast cancer, interstitial mastopathy, or BRCA1/2 mutation carriers. Clinicopathologic characteristics, surgical outcomes, and postoperative complications were analyzed. The severity of complications was graded using the Clavien-Dindo system. @*Results@#A total of 58 RANSM procedures were performed in 46 women: 15 cases of gasless RANSM and 43 cases of gas-inflated RANSM. The proportion of node-negative disease was higher in the gas-inflated group (97.1%) than in the gasless group (69.2%, p = 0.016).Adjuvant radiotherapy was administered in 30.6% of the cases in the gasless group and only 5% of the cases in the gas-inflated group. Other clinicopathological factors were not significantly different between the groups. Regarding surgical outcomes, the initial incision was 1 cm longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.20 ± 1.05 cm; p = 0.002). The final incision was also longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.57 ± 1.07 cm; p = 0.040). Operation time, complication rate, and complication grade were not significantly different between the 2 groups. @*Conclusion@#In this study, there were no significant differences in surgical outcomes or postoperative complications between gasless and gas-inflated RANSM, except for a longer incision with the gasless technique. Both techniques are reasonable options for RANSM followed by immediate reconstruction.

Assessment of the Prognostic Staging System of American Joint Committee on Cancer 8th Edition for Breast Cancer: Comparisons with the Conventional Anatomic Staging System / 한국유방암학회지

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system.METHODS: Of the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria.RESULTS: In both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001).CONCLUSIONS: Staging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.

An Updated Nomogram for Predicting Invasiveness in Preoperative Ductal Carcinoma In Situ of the Breast

PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.

Is the frozen section examination for sentinel lymph node necessary in early breast cancer patients?

PURPOSE: Sentinel lymph node (SLN) biopsy (SLNB) is widely performed for axillary staging in patients with breast cancer. Based on the results of frozen section examination (FSE), surgeons can decide to continue further axillary dissections. This study aimed to verify the accuracy of FSE for SLNs. METHODS: We reviewed the records of 4,219 patients who underwent SLNB for primary invasive breast cancer between 2007 and 2016 at the Severance Hospital. We evaluated factors associated with the false-negative results of FSE for SLNs using the Generalized Estimating Equations model. RESULTS: A total of 1,397 SLNs from 908 patients were confirmed to be metastatic. Seventy-one patients (1.7%) had confirmed pathologic N2 or N3 stage. Among metastatic SLNs, micrometastasis was found in 234 (16.8%). The overall accuracy of SLNB was 98.5%. The sensitivity and false-negative rate of FSE were 86.4% and 13.6%, respectively. Several clinicopathological factors, including the size of SLN metastases, suspicious preoperative axillary lymph nodes, and luminal B subtype, were associated with a higher rate of false-negative results. CONCLUSION: Most patients were not indicated for axillary lymph node dissection. Some patients may show transition in their permanent pathology due to the size of the metastatic node. However, the false-negative results of FSE for SLNs based on the size of the metastatic node did not change our practice. Therefore, intraoperative FSE for SLN should not be routinely performed for all breast cancer patients.

External validation of IBTR! 2.0 nomogram for prediction of ipsilateral breast tumor recurrence

PURPOSE: IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. MATERIALS AND METHODS: The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of 10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. RESULTS: The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. CONCLUSIONS: IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.

Association between Changes in Serum 25-Hydroxyvitamin D Levels and Survival in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy / 한국유방암학회지

PURPOSE: We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D) levels before and after neoadjuvant chemotherapy (NCT) and the associations with pathologic complete response (pCR) and survival in patients with breast cancer. METHODS: Serum 25(OH)D concentrations were measured pre- and post-NCT in 374 patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were categorized into “either sufficient” or “both deficient” groups. The associations with clinicopathological data, including pCR and survival, were analyzed using multivariable analyses. RESULTS: Patients with either pre- or post-NCT sufficient 25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum levels after NCT. Changes in 25(OH)D status were associated with postmenopause status, rural residence, baseline summer examination, and molecular phenotype, but not pCR. No association between survival and 25(OH)D status was found, including in the subgroup analyses based on molecular phenotypes. CONCLUSION: Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis and a significant decrease in the serum concentration after NCT. No association with oncologic outcomes was found. Therefore, although optimal management for vitamin D deficiency is urgent for skeletal health, further research is warranted to clearly determine the prognostic role of vitamin D in patients with breast cancer who are candidates for NCT.

Next-generation sequencing of BRCA1/2 in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results

PURPOSE: We evaluated the clinical role of rapid next-generation sequencing (NGS) for identifying BRCA1/2 mutations compared to traditional Sanger sequencing. METHODS: Twenty-four paired samples from 12 patients were analyzed in this prospective study to compare the performance of NGS to the Sanger method. Both NGS and Sanger sequencing were performed in 2 different laboratories using blood samples from patients with breast cancer. We then analyzed the accuracy of NGS in terms of variant calling and determining concordance rates of BRCA1/2 mutation detection. RESULTS: The overall concordance rate of BRCA1/2 mutation identification was 100%. Variants of unknown significance (VUS) were reported in two cases of BRCA1 and 3 cases of BRCA2 after Sanger sequencing, whereas NGS reported only 1 case of BRCA1 VUS, likely due to differences in reference databases used for mutation identification. The median turnaround time of Sanger sequencing was 22 days (range, 14–26 days), while the median time of NGS was only 6 days (range, 3–21 days). CONCLUSION: NGS yielded comparably accurate results to Sanger sequencing and in a much shorter time with respect to BRCA1/2 mutation identification. The shorter turnaround time and higher accuracy of NGS may help clinicians make more timely and informed decisions regarding surgery or neoadjuvant chemotherapy in patients with breast cancer.

Comparisons of Oncologic Outcomes between Triple-Negative Breast Cancer (TNBC) and Non-TNBC among Patients Treated with Breast-Conserving Therapy

PURPOSE: The optimum local surgical strategy regarding breast-conserving therapy (BCT) for triple-negative breast cancer (TNBC) is controversial. To investigate whether BCT is appropriate for patients with TNBC, we evaluated the clinical outcomes of BCT in women with TNBC compared to those of women without TNBC, using a large, single-center cohort. MATERIALS AND METHODS: We performed a retrospective analysis of 1533 women (TNBC n=321; non-TNBC n=1212) who underwent BCT for primary breast cancer between 2000 and 2010. Clinicopathological characteristics, locoregional recurrence-free survival (LRFS), and overall survival (OS) were analyzed. RESULTS: Tumors from the TNBC group had a higher T stage (T2 37.4% vs. 21.0%, p<0.001), a lower N stage (N0 86.9% vs. 75.5%, p<0.001), and a higher histologic grade (Grade III 66.8% vs. 15.4%, p<0.001) than the non-TNBC group. There were no differences in 5-year LRFS rates between the TNBC and non-TNBC groups (98.7% vs. 97.8%, p=0.63). The non-TNBC group showed a slightly better 5-year OS than the TNBC group; however, the difference was not significant (96.2% vs. 97.3%, p=0.72). In multivariate analyses, TNBC was not associated with poor clinical outcomes in terms of LRFS and OS [hazard ratio (HR) for LRFS=0.37, 95% confidence interval (CI): 0.10-1.31; HR for OS=1.03, 95% CI: 0.31-3.39]. CONCLUSION: TNBC patients who underwent BCT showed non-inferior locoregional recurrence compared to non-TNBC patients with BCT. Thus, BCT is an acceptable surgical approach in patients with TNBC.

Preoperative Magnetic Resonance Imaging and Survival Outcomes in T1–2 Breast Cancer Patients Who Receive Breast-Conserving Therapy / 한국유방암학회지

PURPOSE: The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. METHODS: A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. RESULTS: Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. CONCLUSION: Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS.

The role of prophylactic antibiotics on surgical site infection in elective laparoscopic cholecystectomy

BACKGROUNDS/AIMS: Although laparoscopic cholecystectomy is a common and widely accepted technique, the use of prophylactic antibiotics in elective laparoscopic cholecystectomy still remains controversial. The aim of this study is to determine whether prophylactic antibiotics could prevent surgical site infection after elective laparoscopic cholecystectomy and to identify any risk factors for surgical site infection. METHODS: This study included 471 patients undergoing laparoscopic cholecystectomy between January 2009 and May 2012. Period 1 patients (279) received second generation cephalosporin 1 g intravenously after induction of anesthesia, and Period 2 patients (192) were not given prophylactic antibiotics. The characteristics and surgical site infections of the patients were compared and analyzed. RESULTS: The overall rate of surgical site infection was 1.69% for the total of 471 patients. The incidence of surgical site infection was similar for the two Periods: 5 of 279 patients (1.79%) in Period 1, 3 of 192 patients (1.56%) in Period 2 (p=0.973). All of the patients with surgical site infections were well treated under conservative treatments without any sequelae. The preoperative albumin level (p=0.023) contributed to surgical site infection. CONCLUSIONS: Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy but patients in poor nutritional state with low albumin level should consider prophylactic antibiotics.

Does Liver Resection Provide Long-Term Survival Benefits for Breast Cancer Patients with Liver Metastasis? A Single Hospital Experience

PURPOSE: Liver resection with colorectal liver metastasis widely accepted and has been considered safe and effective therapeutic option. However, the role of liver resection in breast cancer with liver metastasis is still controversial. Therefore, we reviewed the outcome of liver resection in breast cancer patients with liver metastases in a single hospital experiences. MATERIALS AND METHODS: Between January 1991 and December 2006, 2176 patients underwent breast cancer surgery in Gangnam Severance Hospital. Among these patients, 110 cases of liver metastases were observed during follow-up and 13 of these patients received liver resection with potential feasibility to achieve an R0 resection. RESULTS: The median time interval between initial breast cancer and detection of liver metastasis was 62.5 months (range, 13-121 months). The 1-year and 3-year overall survival rates of the 13 patients with liver resection were 83.1% and 49.2%, respectively. The 1-year and 3-year overall survival rates of patients without extrahepatic metastasis were 83.3% and 66.7% and those of patients with extrahepatic metastasis were 80.0% and 0.0%, respectively (p=0.001). CONCLUSION: Liver resection for metastatic breast cancer results in improved patient survival, particularly in patients with solitary liver metastasis and good general condition.

A model for predicting pancreatic leakage after pancreaticoduodenectomy based on the international study group of pancreatic surgery classification

BACKGROUNDS/AIMS: With recent advances in pancreatic surgery, pancreaticoduodenectomy (PD) has become increasingly safe. However, pancreatic leakage is still one of the leading postoperative complications. An accurate prediction model for pancreatic leakage after PD can be helpful for pancreas surgeons. The aim of this study was to provide a new model that was simple and useful with high accuracy for predicting pancreatic leakage after PD. METHODS: To predict the occurrence of pancreatic leakage, several factors were selected using bivariate analysis and univariate logistic regression analysis. The final model was developed using multivariable logistic regression analysis in the model construction data set. RESULTS: Overall, 41 of 100 patients had pancreatic leakage by the International Study Group on Pancreatic Fistula (ISGPF) criteria. Soft pancreatic parenchyma, small pancreatic duct diameter (< or =3 mm), and combined resection of SMV and portal vein were independently predictive of pancreatic leakage. The risk score (R) for individual patients can be calculated by combining the 3 prognostic values with the regression test: R=0.5986+(0.5533 x pancreatic parenchyma)+(0.5448 x pancreatic duct diameter)+(0.8453 x combined resection). The overall predictive accuracy of the model, as measured by the receiver operating characteristic (ROC) curve, was 0.728. CONCLUSIONS: Although continued refinements and improvements in the model are needed, the present model may assist pancreatic surgeons in the prediction of pancreatic leakage after PD.