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PurposeBreast cancer is a group of diseases with different intrinsic molecular subtypes. However, anatomic staging alone is insufficient to determine prognosis. The present study analyzed the prognostic value of the American Joint Committee for Cancer (AJCC) 8th edition cancer staging system.MethodsThis retrospective, single-center study included breast cancer cases diagnosed from January 1999 to December 2008. We restaged patients based on the 8th edition AJCC cancer staging system and analyzed the prognostic value of the anatomic and prognostic staged groups. Follow-up data including disease-free survival (DFS), overall survival (OS), and clinic-pathological data were collected to analyze the differences between the two staging subgroups.ResultsThe study enrolled 7458 breast cancer patients with a 98.7-month median follow-up. Both the 5-year DFS and OS were significantly different between the anatomic and prognostic staged groups. The 5-year OS according to disease subtype was as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR(+)/HER2(−)], 90.9%; HR(+)/HER2(+), 84.7%; HR(−)/HER2(+), 81.1%; and HR(−)/HER2(−), 80.9%. According to the anatomic stage, the 5-year OS of patients with stage III HR(+)/HER2(−) disease was superior to that of patients with stage II HR(−)/HER2(−) disease (88.3 vs. 86.5%). Per the prognostic stage, both the 5-year DFS and OS rates of patients with stage II HR(−)/HER2(−) disease were higher than those of patients with stage III HR(+)/HER2(−) disease (90.1 and 94.3% vs. 79.1 and 88.9%).ConclusionsThe prognostic staging system is a refined version of the anatomic staging system and encourages a more personalized approach to breast cancer treatment.

For residual N1 nodal disease following neoadjuvant chemotherapy (NAC) for patients with breast cancer, the optimal local therapy for axilla is an evolving area. We analyzed the long-term results of these patients according to axillary surgical methods using propensity score matching (PSM) to clarify whether omission of axillary lymph node dissection (ALND) is oncologically safe. This was a single institution retrospective study of patients with ypN1 from Asan Medical Center (AMC). We included 324 patients who had undergone axillary surgery with either sentinel lymph node biopsy (SLNB) only or ALND. The patients received NAC at AMC between 2008 and 2013. General indications for ALND included prominent nodes detected clinically before NAC, evident macrometastasis on multiple nodes during SLNB. Patients who had either micrometastasis or macrometastasis in 1 or 2 node(s) were included. SLNB was performed for patients with good responders to NAC with limited nodal burden. Patients were matched for baseline characteristics. After matching, we included 98 patients in each SLNB only group and ALND group respectively. We compared axillary recurrence-free survival (ARFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-free survival (BCSS) according to the surgical method. The median follow-up period was 71 months. Univariate and multivariate analyses revealed no statistically significant differences between the two groups for ARFS, DMFS, OS, and BCSS. After the propensity score matching, no significant statistical differences were observed in 5-year ARFS, DMFS, OS, and BCSS between the SLNB only group and ALND group. SLNB might be a possible option for ALND in patients with breast cancer who have limited axillary node metastasis after NAC without compromising survival outcomes.

BackgroundA short tumor-to-nipple distance (TND) is reported as a strong predictor of nipple-areola complex (NAC) involvement. Eligibility for nipple-sparing mastectomy (NSM) remains controversial, especially regarding TND. In this study, we compared long-term oncologic outcomes after NSM between patients with a TND ≤ 1 cm and those with a TND > 1 cm.MethodsOverall, 1369 patients with primary breast cancer who underwent NSM with immediate reconstruction from March 2003 to December 2015 were included for analysis. After propensity score matching, 495 patients with a TND ≤ 1 cm (group A) and 495 patients with a TND > 1 cm (group B) on imaging were selected to compare long-term oncologic outcomes. ResultsAfter matching, the median follow-up periods for surviving patients were 109 months and 112 months for groups A and B, respectively. There were no significant differences between groups with respect to the 5-year cumulative local recurrence (8.1% vs. 6.3%; p = 0.268), NAC recurrence (5.1% vs. 2.8%; p = 0.072), regional recurrence (2.0% vs. 3.6%; p = 0.125), or distant recurrence (5.9% vs. 4.8%; p = 0.480) rates. Furthermore, no significant differences were observed between the groups with respect to the 10-year local recurrence-free survival (87.1% vs. 90.7%; p = 0.164) or disease-free survival (77.9% vs. 81.6%; p = 0.222) rates. ConclusionsA preoperative TND ≤ 1 cm on imaging should not be contraindicated to NSM as long as there is no involvement of NAC clinically or on imaging and if retroareolar margins are confirmed to be negative for tumor cells.

To analyze and compare the survival rates of recurrent breast cancer patients in Korea between two periods (period I: 2000-2007; period II: 2008-2013) and to identify the factors associated with outcomes and changes over time in the duration of survival after recurrence. We retrospectively analyzed 2,407 patients who had recurrent breast cancer with treated between January 2000 and December 2013 and divided them into two periods according to the year of recurrence. We reviewed the age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment, type of recurrence, and follow-up period. The median follow-up was 30.6 months (range, 0-223.4) from the time of relapse, and the median survival time was 42.3 months. Survival after recurrence (SAR) significantly improved from 38.0 months in period I to 49.7 months in period II (p < 0.001). In the analysis performed according to the hormone receptor and HER2 status subtypes, all subtypes except the triple-negative subtype showed higher SAR in period II than period I. Age at diagnosis, tumor stage, and treatment after recurrence were significantly correlated with survival outcomes. The survival outcomes of Korean patients with breast cancer after the first recurrence have improved in Korea. Such improvements may be attributed to advances in treatment.

PurposeThis study aimed to compare long-term survival outcomes of repeat lumpectomy with total mastectomy after ipsilateral breast tumor recurrence (IBTR) using propensity score matching (PSM).MethodsWe retrospectively analyzed patients with IBTR who had undergone initial breast-conserving surgery for breast cancer at our institution between January 1990 and December 2013. The Kaplan–Meier method and Cox proportional hazards model were used to compare survival rates between the two groups. PSM was performed using the following covariates: age at initial operation, initial T stage, N stage, hormone receptor status, human epidermal growth factor receptor 2 status, chemotherapy, radiotherapy, and IBTR tumor size.ResultsWe enrolled 335 IBTR patients with a median follow-up of 126.6 months. No significant differences were observed in the 5-year overall survival (OS), breast cancer-specific survival (BCSS), OS after IBTR, and BCSS after IBTR and 10-year survival probability between the two groups in a multivariate analysis. After PSM, patients who had undergone repeat lumpectomy and total mastectomy (n = 90 in both groups) were included. No significant differences were observed in the 10-year OS (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.49–2.39), BCSS (HR 0.83, 95% CI 0.35–1.95), OS after IBTR (HR 0.83, 95% CI 0.38–1.83), and BCSS after IBTR (HR 0.64, 95% CI 0.28–1.47) between the two groups.ConclusionsNo significant differences were observed in survival outcomes between patients with IBTR who underwent repeat lumpectomy or total mastectomy. Our results can be helpful in selecting the appropriate surgical method for IBTR.

We aimed to develop a prediction MammaPrint (MMP) genomic risk assessment nomogram model for hormone-receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2–) breast cancer and minimal axillary burden (N0-1) tumors using clinicopathological factors of patients who underwent an MMP test for decision making regarding adjuvant chemotherapy. A total of 409 T1-3 N0-1 M0 HR + and HER2– breast cancer patients whose MMP genomic risk results and clinicopathological factors were available from 2017 to 2020 were analyzed. With randomly selected 306 patients, we developed a nomogram for predicting a low-risk subgroup of MMP results and externally validated with remaining patients (n = 103). Multivariate analysis revealed that the age at diagnosis, progesterone receptor (PR) score, nuclear grade, and Ki-67 were significantly associated with MMP risk results. We developed an MMP low-risk predictive nomogram. With a cut off value at 5% and 95% probability of low-risk MMP, the nomogram accurately predicted the results with 100% positive predictive value (PPV) and negative predictive value respectively. When applied to cut-off value at 35%, the specificity and PPV was 95% and 86% respectively. The area under the receiver operating characteristic curve was 0.82 (95% confidence interval [CI] 0.77 to 0.87). When applied to the validation group, the nomogram was accurate with an area under the curve of 0.77 (95% CI 0.68 to 0.86). Our nomogram, which incorporates four traditional prognostic factors, i.e., age, PR, nuclear grade, and Ki-67, could predict the probability of obtaining a low MMP risk in a cohort of high clinical risk patients. This nomogram can aid the prompt selection of patients who does not need additional MMP testing.

Our aim was to develop a tool to accurately predict the possibility of non-sentinel lymph node metastasis (NSLNM) during surgery so that a surgeon might decide the extent of further axillary lymph node dissection intraoperatively for patients with 1–3 positive sentinel lymph node(s) (SLN) after neoadjuvant chemotherapy. After retrospective analysis of Asan Medical Center (AMC) database, we included 558 patients’ records who were treated between 2005 and 2019. 13 factors were assessed for their utility to predict NSLNM with chi-square and logistic regression with a bootstrapped, backward elimination method. Based on the result of the univariate analysis for statistical significance, number of positive SLN(s), number of frozen nodes, Progesterone Receptor (PR) positivity, clinical N stage were selected for the multivariate analysis and were utilized to generate a nomogram for prediction of residual nodal disease. The resulting nomogram was tested for validation by using a patient group of more recent, different time window at AMC. We designed a nomogram to be predictive of the NSLNM which consisted of 4 components: number of SLN(s), number of frozen nodes, PR positivity, and clinical N stage before neoadjuvant chemotherapy. The Area under the receiver operating characteristics curve (AUC) value of this formula was 0.709 (95% CI, 0.658–0.761) for development set and 0.715 (95% CI, 0.634–0.796) for validation set, respectively. This newly created AMC nomogram may provide a useful information to a surgeon for intraoperative guidance to decide the extent of further axillary surgery.

Purpose We evaluated the benefit of chemotherapy in patients with ipsilateral breast tumor recurrence (IBTR) by comparing the survival outcomes between the chemotherapy and no chemotherapy groups, using propensity score matching (PSM), and analyze the survival outcomes stratified by hormone receptor status of IBTR. Methods We retrospectively analyzed patients who developed invasive IBTR after undergoing breast-conserving surgery at our institution between 1990 and 2013. A 1:1 PSM analysis was performed to compare the survival rates between the two study groups; additional analysis stratified by hormone receptor status was performed. The Kaplan–Meier method and Cox proportional hazards model were used to compare the second recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates between the two groups. Results The 217 IBTR patients had a median follow-up of 125.3 months. After PSM, patients without chemotherapy and with chemotherapy ( n  = 35 in both groups) were included. No significant differences were observed in the 10-year second RFS [50.2% without chemotherapy vs. 39.8% with chemotherapy, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.50–1.80], DMFS (85.4% vs. 70.3%, HR 1.51, 95% CI 0.66–3.44), and OS (81.6% vs. 68.6%, HR 1.73, 95% CI 0.76–3.90) rates between the two groups. Analyses stratified by hormone receptor status showed similar findings: no significant differences were observed in the second RFS, DMFS, and OS rates between the two groups in both hormone receptor-positive and -negative groups. Conclusion Chemotherapy had no impact in the long-term survival outcomes of IBTR patients regardless of the hormone receptor status.

Although distress screening is crucial for cancer survivors, it is not easy for clinicians to recognize distress. Physical activity (PA) data collected by mobile devices such as smart bands and smartphone apps have the potential to be used to screen distress in breast cancer survivors. The aim of this study was to assess data collection rates of smartphone apps and smart bands in terms of PA data, investigate the correlation between PA data from mobile devices and distress-related questionnaires from smartphone apps, and demonstrate factors associated with data collection with smart bands and smartphone apps in breast cancer survivors. In this prospective observational study, patients who underwent surgery for breast cancer at Asan Medical Center, Seoul, Republic of Korea, between June 2017 and March 2018 were enrolled and asked to use both a smartphone app and smart band for 6 months. The overall compliance rates of the daily PA data collection via the smartphone walking apps and wearable smart bands were analyzed in a within-subject manner. The longitudinal daily collection rates were calculated to examine the dropout pattern. We also performed multivariate linear regression analysis to examine factors associated with compliance with daily collection. Finally, we tested the correlation between the count of daily average steps and distress level using Pearson correlation analysis. A total of 160 female patients who underwent breast cancer surgeries were enrolled. The overall compliance rates for using a smartphone app and smart bands were 88.0% (24,224/27,513) and 52.5% (14,431/27,513), respectively. The longitudinal compliance rate for smartphone apps was 77.8% at day 180, while the longitudinal compliance rate for smart bands rapidly decreased over time, reaching 17.5% at day 180. Subjects who were young, with other comorbidities, or receiving antihormonal therapy or targeted therapy showed significantly higher compliance rates to the smartphone app. However, no factor was associated with the compliance rate to the smart band. In terms of the correlation between the count of daily steps and distress level, step counts collected via smart band showed a significant correlation with distress level. Smartphone apps or smart bands are feasible tools to collect data on the physical activity of breast cancer survivors. PA data from mobile devices are correlated with participants' distress data, which suggests the potential role of mobile devices in the management of distress in breast cancer survivors. ClinicalTrials.gov NCT03072966; https://clinicaltrials.gov/ct2/show/NCT03072966.

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient’s primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1–5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates ( p -value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p -value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5–11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence.