Surveillance for Distant Metastasis in Breast Cancer Patients Who Underwent Contemporary Management: A Report from the Korean Breast Cancer Society Survivor Research Group.

BACKGROUND: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions. RESULTS: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS. CONCLUSIONS: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.

Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody-drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status. METHODS: This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed. RESULTS: The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion. CONCLUSIONS: Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.

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, vasodilator-stimulated 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.

Evaluating the Efficacy of Machine Performance Checks as an Alternative to Winston-Lutz Quality Assurance Testing in the TrueBeam Linear Accelerator with HyperArc.

HyperArc is a preferred technique for treating brain metastases, employing a single isocenter for multiple lesions. Geometrical isocentricity in the TrueBeam linear accelerator with HyperArc is crucial. We evaluated machine performance checks (MPCs) as an alternative to the Winston-Lutz (WL) test to verify the treatment isocenter. Between January and July 2023, we assessed 53 data points using MPC and Winston-Lutz tests. The isocenter size obtained from the MPC and its sum, including the rotation-induced couch shift, were compared with the maximum total delta value from the Winston-Lutz test. The maximum total delta was 0.68 ± 0.10 mm, while the isocenter size was 0.28 ± 0.02 mm. The sum of the isocenter size and rotation-induced couch shift measured by MPC was 0.61 ± 0.03 mm. During the Winston-Lutz test (without couch rotation), the maximum total delta value was 0.56 ± 0.13 mm. A t-test analysis revealed a significant difference in the isocenter size averages between the Winston-Lutz and MPC outcomes, whereas the Pearson's correlation coefficient yielded no correlation. Our study highlights the necessity for separate MPC and Winston-Lutz tests for isocenter verification. Therefore, the Winston-Lutz test should precede stereotactic radiosurgery for isocenter verification.

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.

Outcome Analysis of Combined Surgical Approaches in Advanced-stage Upper Extremity Breast Cancer-related Lymphedema.

Background: This study aimed to discuss several surgical approaches for advanced-stage breast cancer-related lymphedema and compared their treatment outcomes. Methods: The patients who underwent surgery with International Society of Lymphology stage III lymphedema were included in this study. The three surgical methods used here were (1) suction-assisted lipectomy with lymphovenous anastomosis, (2) autologous breast reconstruction with muscle-sparing transverse rectus abdominis muscle flap combined with inguinal lymph node transfer, and (3) vascularized lymph node transfer with free omental flap. Analysis of the postoperative outcomes in the patients was based on the difference in volume between patients pre- and postoperatively, LYMPH-Q questionnaire, and bioelectrical impedance analysis. Results: Eighty-seven patients with stage IIb or higher disease underwent surgery. 38 patients underwent suction-assisted lipectomy + lymphovenous anastomosis, 23 underwent autologous breast reconstruction with vascularized lymph node transfer + lymphovenous anastomosis, and 26 underwent right gastroepiploic omental vascularized lymph node transfer with lymphovenous anastomosis. The LYMPH-Q questionnaire, which evaluates patients' subjective satisfaction, showed that the autologous breast reconstruction group showed the greatest improvement, whereas in bioimpedance analysis, the omental flap group demonstrated the greatest postoperative improvement compared with preoperative values. However, suction-assisted lipectomy was considered the most effective surgical method for reducing limb volume in patients with high-stage lymphedema accompanied by fibrosis and volume increase. Conclusions: We observed slightly different clinical effects for each surgical method; however, all surgical methods demonstrated a reduction in the degree of edema and an increase in patient satisfaction.

Predictive biological factors for late survival in patients with HER2-positive breast cancer.

The human epidermal growth factor receptor-2 (HER2) enriched subtype of breast cancer is associated with early recurrence, mostly within 5 years. However, anti-HER2 therapies have improved outcomes and their benefits persist in the long term. This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. We analyzed 20,672 patients with HER2-positive stage I-III breast cancer. The patients were divided into two groups based on a follow-up period of 60 months. The multivariate analysis of factors associated with poor overall survival included old age, advanced pathologic tumor size stage (pT), advanced pathologic regional lymph node stage (pN), high histological grade, presence of lymphatic and vascular invasion, and HR-negative status within 60 months. In the breast cancer-specific survival (BCSS) of the > 60 months follow-up group, the hazard ratios (HRa) based on pN-negative were 3.038, 3.722, and 4.877 in pN1 (p = 0.001), pN2 (p < 0.001), and pN3 (p < 0.001), respectively. Only pT4 level was statistically significant in the pT group (HRa, 4.528; p = 0.007). Age (HRa, 1.045, p < 0.001) and hormone receptor-positive status (HRa, 1.705, p = 0.022) were also associated to worse BCSS. Although lymphatic invasion was not significantly associated with BCSS, there was a tendency toward a relationship (p = 0.079) with worse BCSS. In HER2-positive breast cancer patients, node status had a more significant relationship with long-term prognosis than T stage. Patients with HER2-positive breast cancer who have T4 or node-positive should be considered for clinical observation and education beyond 5 years.

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

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.

Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer.

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.

Nipple Projection Change in Immediate Breast Reconstruction and Use of an Acellular Dermal Matrix Strut for Maintaining Nipple Projection.

BACKGROUND: Nipple-sparing mastectomy (NSM) has gained popularity as more studies have supported its oncologic safety. Although there have been some studies reporting complications including mastectomy flap and nipple necrosis, there have been few reports discussing the change in nipple projection following NSM. This study aimed to analyze the change in nipple projection after NSM and identify risk factors for nipple depression. In addition, the authors present a new method for maintaining nipple projection. METHODS: Patients who underwent NSM between March of 2017 and December of 2020 at the authors' institute were included in this study. The authors measured the preoperative and postoperative nipple projection height and used a nipple projection ratio (NPR) to compare the change in height. Univariate and multivariate analyses were performed to examine the correlation of variables with the NPR. RESULTS: A total of 307 patients and 330 breasts were included in this study. There were 13 cases of nipple necrosis. The postoperative nipple height was decreased by 32.8%, which was statistically significant. In multiple linear regression analysis, the use of an acellular dermal matrix strut was positively correlated with the NPR and implant-based reconstruction and postmastectomy radiation therapy were negatively correlated with the NPR. CONCLUSIONS: The results of this study demonstrated that the reduction in nipple height after NSM was statistically significant. Surgeons need to be aware of these changes following NSM and explain this possibility to patients who have risk factors. The application of an acellular dermal matrix strut should be considered for the prevention of nipple reduction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Recurrence is Not Associated with Margin Status in Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm of the breast. The proper extent of resection is still under debate. This study aimed to investigate the optimal surgical margin to prevent recurrence after surgery for PT and to evaluate risk factors for local recurrence (LR). METHODS: Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for PT at Seoul National University Bundang Hospital between July 2003 and February 2022 were reviewed. RESULTS: Of the 439 patients included, 285 were benign, 129 were borderline, and 25 were malignant. There was no statistically significant difference in 5-year disease-free survival (DFS) between margin-negative and margin-involved patients (87.3% vs. 85.1%, p = 0.081). When patients were classified into groups, according to margin status, as conventional (≥ 1 cm from tumor), close (< 1 cm from tumor), or involved, 5-year DFS rates were also similar (100% vs. 86.9% vs. 85.1%, p = 0.170). In subgroup analysis for different histologic grades, 5-year DFS was not affected by margin involvement. In univariate analysis, large tumor size (> 5 cm; hazard ratio [HR] 2.857, p = 0.028) and infiltrative tumor border (HR 3.096, p = 0.012) were independent risk factors for LR. Further multivariate analysis found both factors to be prognostic. CONCLUSIONS: Recurrence was not significantly influenced by margin status in all histological grades. In benign and borderline tumors, local excision without wide surgical margins could be sufficient, and watchful waiting could be an option for patients with positive margins after initial surgery.

Conventional versus modified nipple sparing mastectomy in immediate breast reconstruction: Complications, aesthetic, and patient-reported outcomes.

Background: Nipple-sparing mastectomy (NSM) followed by immediate breast reconstruction (IBR) is the optimal surgical treatment for breast cancer. However, investigations are ongoing to improve the surgical technique to achieve better results. This study aimed to evaluate the outcomes of modified NSM (m-NSM), which preserves the anterior lamellar fat layer, in patients who underwent IBR. Methods: All patients who underwent modified NSM (m-NSM) or conventional NSM (c-NSM) followed by IBR using autologous tissue or implants were retrospectively reviewed between January 2014 and January 2021. Two mastectomy types were compared in terms of postoperative complications and aesthetic outcomes using panel assessment scores by physicians and reported outcomes using Breast-Q. In addition, postoperative evaluations of the thickness of mastectomy flap was performed using CT scan images. Results: A total of 516 patients (580 breasts) with NSM (143 breasts with c-NSM and 437 breasts with m-NSM) followed by IBR were reviewed. The mean ± SD flap thickness was 8.48 ± 1.81 mm in patients who underwent m-NSM, while it was 6.32 ± 1.15 mm in the c-NSM cohort (p = 0.02). The overall major complications rate was lower in the m-NSM group (3.0% vs. 9.0%, p < 0.013). Ischemic complications of the mastectomy flap and nipple-areolar complex (NAC) were more in c-NSM, although the difference was not statistically significant. The mean panel assessment scores were higher in the m-NSM group (3.14 (good) and 2.38 (fair) in the m-NSM and c-NSM groups, respectively; p < 0.001). Moreover, m-NSM was associated with greater improvements in psychosocial (p < 0.001) and sexual (p = 0.007) well-being. Conclusion: Preserving the anterior lamellar fat in NSM was associated with thicker mastectomy flap, overall lower rates of complications, including ischemia of the mastectomy flap and nipple-areolar complex, and was associated with better aesthetic outcomes and improved quality of life.

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 follow-up 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.

Risk factors for chest wall depression after implant insertion for breast reconstruction: a retrospective quantitative study.

Background: Implant-based reconstruction represents the most common form of breast reconstruction after mastectomy. Although the complication rate has lowered owing to the current advances, various implant-related complications are still a problem. There have been few reports discussing chest wall deformation following implant insertion. The aim of this study was to quantify chest wall depression (CWD) after breast implant insertion and identify possible risk factors. Methods: Patients who underwent unilateral direct-to-implant reconstruction were included in the study. We measured the pre- and postoperative antero-posterior length of the chest wall and used a CWD ratio to measure the change in length. Multivariate analysis was performed with factors with P values of <0.2 in univariate analyses to identify factors associated with CWD. Results: A total of 57 patients were included in this study. The pre- and postoperative difference of antero-posterior length was statistically significant using a paired t-test. Average depth of CWD was 4.16 mm (range, -2.16 to 13.82 mm). In multivariate analysis, capsular contracture and age were the independent prognostic factors correlated with CWD. Conclusions: This study showed the possibility of CWD following implant insertion. Surgeons and specialists should be aware of the possibility and risk factors of CWD following implant insertion to better inform patients.

Feasibility of anomaly score detected with deep learning in irradiated breast cancer patients with reconstruction.

The aim of this study is to evaluate cosmetic outcomes of the reconstructed breast in breast cancer patients, using anomaly score (AS) detected by generative adversarial network (GAN) deep learning algorithm. A total of 251 normal breast images from patients who underwent breast-conserving surgery were used for training anomaly GAN network. GAN-based anomaly detection was used to calculate abnormalities as an AS, followed by standardization by using z-score. Then, we reviewed 61 breast cancer patients who underwent mastectomy followed by reconstruction with autologous tissue or tissue expander. All patients were treated with adjuvant radiation therapy (RT) after reconstruction and computed tomography (CT) was performed at three-time points with a regular follow-up; before RT (Pre-RT), one year after RT (Post-1Y), and two years after RT (Post-2Y). Compared to Pre-RT, Post-1Y and Post-2Y demonstrated higher AS, indicating more abnormal cosmetic outcomes (Pre-RT vs. Post-1Y, P = 0.015 and Pre-RT vs. Post-2Y, P = 0.011). Pre-RT AS was higher in patients having major breast complications (P = 0.016). Patients with autologous reconstruction showed lower AS than those with tissue expander both at Pre-RT (2.00 vs. 4.19, P = 0.008) and Post-2Y (2.89 vs. 5.00, P = 0.010). Linear mixed effect model revealed that days after baseline were associated with increased AS (P = 0.007). Also, tissue expander was associated with steeper rise of AS, compared to autologous tissue (P = 0.015). Fractionation regimen was not associated with the change of AS (P = 0.389). AS detected by deep learning might be feasible in predicting cosmetic outcomes of RT-treated patients with breast reconstruction. AS should be validated in prospective studies.

Clinical Application of Next-Generation Sequencing in Patients With Breast Cancer: Real-World Data.

PURPOSE: Next-generation sequencing (NGS)-based tumor panel testing has been reimbursed by the Korean government since 2017. We evaluated the use of NGS-based tumor panel testing in real-world clinical practice, focusing on molecular profiling (MP)-guided breast cancer treatment. METHODS: A total of 137 breast cancer patients underwent NGS panel testing between December 2017 and July 2020 at Seoul National University Bundang Hospital (SNUBH). Samples from patients were profiled using an in-house SNUBH pan-cancer panel. Sixty-four patients were profiled on SNUBH Pan_Cancer v1.0, targeting 89 genes, while 73 patients were profiled on SNUBH Pan_Cancer v2.0, targeting 546 genes. RESULTS: Breast cancer subtypes included hormone receptor+/human epidermal growth factor receptor 2 (HER2)- (n = 87), triple-negative (n = 44), and HER2+ (n = 6). Most patients had locally advanced or metastatic cancers (92%). Approximately 92% (126/137) of the patients had significant genomic alterations (tiers I and II), and 62% (85/137) had targetable genomic alterations. The most common targetable genomic alterations were PIK3CA (39%) and ESR1 mutations (9%), followed by ERBB2 (7%), PTEN (7%), BRCA2 (6%), and BRCA1 mutations (4%). Of the 81 patients with locally advanced/metastatic breast cancer with targetable genomic alterations, 6 (7.4%) received MP-guided treatments, including PARP inhibitor (n = 4), ERBB2-directed therapy (n = 1), and PI3K inhibitor (n = 1). Among these 6 patients, 4 participated in clinical trials, 1 underwent treatment at their own expense, and 1 received drugs through an expanded access program. The remaining 66 patients (81%) with targetable genomic alteration did not receive MP-guided treatment due to lack of matched drugs and/or clinical trials, poor performance status, and/or financial burden. CONCLUSION: NGS panel testing allowed MP-guided treatment in only 4.7% (6/127) of patients with advanced breast cancer in a real-world setting. The availability of matched drugs is critical for the realistic implementation of personalized treatment.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial.

BACKGROUND: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated. METHODS: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. DISCUSSION: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020.