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We investigated the safety and performance of the Da Vinci SP single-port robot (SP robot) in nipple-sparing mastectomy (NSM) with immediate reconstruction. Medical records of 60 women aged ≥ 19 years who had undergone SP robot-assisted unilateral or bilateral NSM with immediate reconstruction between October 2020 and August 2021 were retrospectively analyzed. Stage I (31, 47.1%) was the most common pathological tumor-node-metastasis stage, followed by stages II (22, 33.3%), 0 (7, 10.6%), and III (4, 6.0%). The median total duration of NSM performed by a breast surgeon and reconstruction performed by a plastic surgeon was 154.0 min (interquartile range [IQR], 130.5–206.0 min) and 133.0 min (IQR, 80.0–255.0 min), respectively. The median length of hospitalization was 5.5 days (IQR, 3.0–9.0 days). Conversion to robotic multiport or open surgery was not required in any case. The median duration to drain removal was 5.0 days (IQR, 4.0–6.0 days). Recurrence of cancer within 6 months was not observed in any patient. SP robot-assisted NSM with immediate reconstruction was performed successfully in all patients without conversion to open surgery or the incidence of significant perioperative complications, indicating its precision and ability to minimize the size of the surgical incision. [ABSTRACT FROM AUTHOR]

In breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy. This retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT. 203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2–96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences. The application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes. [ABSTRACT FROM AUTHOR]

Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery. Methods: We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high‐risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki‐67 labeling index >20%. Results: Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5‐month median follow‐up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5‐year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high‐risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001). Conclusion: Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). Methods: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. Results: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927–0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767–22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555–6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386–19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329–5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362–5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230–5.046; p = 0.011). Conclusion: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes. Methods: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status. Results: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01–5.20, p = 0.047). Conclusions: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS. [ABSTRACT FROM AUTHOR]

Purpose: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). Methods: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). Results: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02–1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01–1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. Conclusion: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR. [ABSTRACT FROM AUTHOR]

The prognostic role of the recurrence score (RS) based on the 21‐gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21‐gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer‐free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95‐3.73], P =.069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49‐5.82], log‐rank P <.001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log‐rank P =.51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years. [ABSTRACT FROM AUTHOR]

Purpose: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND). Methods: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed. Results: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3–4 tumor. In the subgroup analysis, we showed that in the T1–2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group. Conclusion: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether six cycles of FEC3-D3 has a comparable efficacy to eight of AC4-D4. Methods: The enrolled patients (pts) were clinically diagnosed with stage II or III breast cancer. The primary endpoint was a pathologic complete response (pCR), and the secondary endpoints were 3 year disease-free survival (3Y DFS), toxicities, and health-related quality of life (HRQoL). We calculated that 252 pts were needed in each treatment group to enable the detection of non-inferiority (non-inferiority margin of 10%). Results: In terms of ITT analysis, 248 pts were finally enrolled. The 218 pts who completed the surgery were included in the current analysis. The baseline characteristics of these subjects were well balanced between the two arms. By ITT analysis, pCR was achieved in 15/121 (12.4%) pts in the FEC3-D3 arm and 18/126 (14.3%) in the AC4-D4 arm. With a median follow up of 64.1 months, the 3Y DFS was comparable between the two arms (75.8% in FEC3-D3 vs. 75.6% in AC4-D4). The most common adverse event (AE) was Grade 3/4 neutropenia, which arose in 27/126 (21.4%) AC4-D4 arm pts vs 23/121 (19.0%) FEC3-D3 arm cases. The primary HRQoL domains were similar between the two groups (FACT-B scores at baseline, P = 0.35; at the midpoint of NACT, P = 0.20; at the completion of NACT, P = 0.44). Conclusion: Six cycles of FEC3-D3 could be an alternative to eight of AC4-D4. Trial registration ClinicalTrials.gov NCT02001506. Registered December 5,2013.https://clinicaltrials.gov/ct2/show/NCT02001506 [ABSTRACT FROM AUTHOR]

Purpose: Considering prognostic and anatomic stages in early-stage premenopausal patients with breast cancer, clinicians decide on performing the multigene assay, adjuvant chemotherapy, or ovarian function suppression (OFS). This decision is also based on genetic information related to hormone receptor-positive and human epidermal growth factor receptor 2 negative results. We aimed to determine the tendency to use adjuvant therapy in clinical practice. Methods: From April to May 2022, clinicians of the Korean Breast Cancer Society responded to a web-based survey. The survey included 62 multiple-choice questions mainly on decision-making under different pathologic conditions. Results: Among 92 responding clinicians, 91.3% were breast surgeons. For 35-year-old patients (pT2N0 and Ki-67 50% profile), 96.8% of clinicians selected chemotherapy, whereas 50.7% selected chemotherapy for patients with pT1N0, Ki-67 10%, and without Oncotype Dx (ODX). Only 35.6% selected chemotherapy for 47-year-old patients with the same profiles, while 84.3% and 49.1% chose chemotherapy with ODX recurrence score 21 and 16, respectively. More clinicians selected tamoxifen (TMX) plus OFS than aromatase inhibitor (AI) plus OFS for 5 years of endocrine therapy in patients with adjuvant chemotherapy regardless of genomic and clinical risks. However, for the same patients without adjuvant chemotherapy, more clinicians selected AI plus OFS. A longer duration of additional OFS and TMX was selected in patients with high clinical and genomic risks, and the duration of OFS was relatively shorter in older patients. Conclusion: The decision regarding adjuvant therapy should be made considering clinical and genomic risks and age, and clinicians should consult with patients about adverse effects and compliance. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Purpose: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC. Methods: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC). Results: When divided into four subtypes, hormone receptor (HR)+/HER2−, HR+ /HER2+ , HR−/HER2+ , and HR−/HER2−, HR−/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0–271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR−/HER2+ group. The five-year DFS for the HR−/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2− group (p = 0.024 The five-year LRFS for HER2− patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR−/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2− group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412–3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408–7.953, p = 0.006 adjusted). Conclusion: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients. [ABSTRACT FROM AUTHOR]

Background: Breast-conserving surgery (BCS) plus radiotherapy (BCS + RT) has been shown to improve survival compared with mastectomy in patients with early breast cancer; however, whether this superiority is maintained in breast cancer patients receiving neoadjuvant chemotherapy (NCT) is unclear. We evaluated and compared the survival outcomes after BCS + RT and mastectomy in Korean women with breast cancer treated with NCT. Methods: We evaluated 1641 patients who received NCT before surgery (BCS or mastectomy). We performed propensity score matching to minimize potential bias due to factors other than the surgical method and compared the 5-year, disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates before and after exact matching. Results: Among the 1641 patients, 839 (51.1%) underwent BCS + RT and 802 (48.9%) underwent mastectomy. Patients who underwent mastectomy had larger tumors and more frequently had positive nodes. For BCS+RT and mastectomy, the unadjusted 5-year DFS, 5-year DMFS, and 5-year OS rates were 87.0% and 73.1%, 89.5% and 77.0%, and 91.8% and 81.0%, respectively (all p < 0.05 = 0.000). After PSM, 5-year DFS, 5-year DMFS, and 5-year OS rates for BCS + RT and mastectomy were 87.6% and 69.1%, 89.7% and 76.0%, and 89.1% and 75.7%, respectively (all p < 0.05). In both unadjusted and adjusted analyses accounting for various confounding factors, BCS + RT was significantly associated with improved DFS (p < 0.05), DMFS (p < 0.05), and OS (p < 0.05) rates compared with mastectomy. Conclusions: BCS + RT does not impair DFS and OS in patients treated with NCT. Tumor biology and treatment response are significant prognostic indicators. Our results suggest that BCS + RT may be preferred in most breast cancer patients when both BCS and mastectomy are suitable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We examined whether 18F-fluorodeoxyglucose metabolism is associated with distant relapse-free survival (DRFS) and overall survival (OS) in women with estrogen receptor (ER)-positive, HER2-negative breast cancer. This was a cohort study examining the risk factors for survival that had occurred at the start of the study. A cohort from Asan Medical Center, Korea, recruited between November 2007 and December 2014, was included. Patients received anthracycline-based neoadjuvant chemotherapy. The maximum standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was measured. The analysis included 466 women. The median (interquartile range) follow-up period without distant metastasis or death was 6.2 (5.3–7.6) years. Multivariable analysis of hazard ratio (95% confidence interval [CI]) showed that the middle and high tertiles of SUV were prognostic for DRFS (2.93, 95% CI 1.62–5.30; P < 0.001) and OS (4.87, 95% CI 1.94–12.26; P < 0.001). The 8-year DRFS rates were 90.7% (95% CI 85.5–96.1%) for those in the low tertile of maximum SUV vs. 73.7% (95% CI 68.0–79.8%) for those in the middle and high tertiles of maximum SUV. 18F-fluorodeoxyglucose PET/CT may assess the risk of distant metastasis and death in ER-positive, HER2-negative patients. [ABSTRACT FROM AUTHOR]

Background: Malignant adenomyoepithelioma of the breast is a rare tumor and most of relevant literature consists of individual case reports. This study objective was designed to evaluate clinicopathological features and treatment outcomes of 15 cases of malignant adenomyoepithelioma at a single institute. Methods: A retrospective medical record review was performed for 15 subjects confirmed with malignant adenomyoepithelioma upon postoperative pathological diagnosis at the Asan Medical Center from January 2008 to June 2018. Data regarding age at diagnosis, preoperative biopsy results, operation methods, the status of hormone receptors and HER2, and clinical outcomes were collected. Results: All cases were female patients diagnosed at median age of 50 years. Preoperative core needle biopsy results showed that 40% of the cases (6 out of 15) were benign which was in discordance with the final malignant pathology report. Thirteen cases underwent wide excision with or without sentinel lymph node biopsy (SLNB) and 2 cases had total mastectomy with SLNB. Five of 11 cases (45.5%) were triple negative. Ten of 15 cases underwent postoperative radiation therapy, 3 cases underwent chemotherapy, and 5 cases underwent endocrine therapy. During median follow-up of 55 months, the 5-year overall survival rate was 87.5% and the 5-year disease free survival rate was 91.7%. Two lung metastases developed. One case showed local recurrence 3 years after surgery and radiotherapy and subsequently developed lung metastasis 1 year late. Another case developed lung metastasis one and a half years after surgery in combination with endocrine therapy and neoadjuvant chemotherapy. Conclusion: Preoperative core needle biopsy showed inaccurate results for diagnosing malignant adenomyoepithelioma. Malignant adenomyoepithelioma has a high rate of triple negative subtype but has a relatively good prognosis although there is a risk of local and systemic recurrence. [ABSTRACT FROM AUTHOR]

Introduction. Breast reconstruction has become common after total mastectomy; however, certain types of breast reconstruction may be associated with delayed local recurrence or poor survival. Here, we investigated whether there are differences in the diagnosis and prognosis of local recurrence between autologous reconstruction and implant reconstruction. Materials and Methods. A retrospective analysis was performed on patients undergoing breast cancer surgery with autologous tissue or immediate implant reconstruction in a single center (January 2003-December 2017). Patient data including the period from cancer surgery to local recurrence diagnosis, tumor size at the time of recurrence, and survival time after cancer surgery and recurrence detection were analyzed. Results. There was a significant difference (p = 0.021) in the time from surgery to recurrence between the autologous tissue (1,246 days) and implant (909 days) groups. Recurrence tumor size did not differ (autologous: 1.00 cm2 vs. implant: 0.90 cm2; p = 0.813). Survival time after surgery (p = 0.63) and recurrence detection (p = 0.74) did not statistically significant. Conclusions. Statistical difference in the detection time was observed between autologous tissue and implant group. On the other hand, there is no difference in recurrence tumor size or survival time. A further study is necessary to identify the different detection time of local recurrence. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the chronological changes over 14 years in the survival of Korean patients with breast cancer. We also sought to investigate the factors that may have influenced the changes in survival rate. Materials and methods: We retrospectively analyzed 17,776 breast cancer patients who were treated at Asan Medical Center between January 2000 and December 2013. Patient information was collected from the Asan database, including age at diagnosis, clinical manifestation, pathology report, types of treatment and modality, types of recurrence, and follow-up period. We classified the patients into two cohorts according to the year of their surgery (P1: 2000–2007 and P2: 2008–2013) and compared survival and recurrence between both cohorts. Results: We observed that patients treated more recently had better survival outcomes. The 5-year breast cancer-specific survival increased from 94.0% in P1 to 96.6% in P2 (p<0.001), and the 5-year disease-free survival increased from 87.9% in P1 to 91.2% in P2 (p<0.001). When analyzed by type of recurrence, distant metastasis-free survival increased to a significant degree. In subgroup analysis by the subtypes of breast cancer, the survival rates improved in all of the subtypes except triple negative breast cancer, and the improvement was more prominent in subtypes with overexpressed human epidermal growth factor receptor 2. Conclusion: This study showed improvement in breast cancer survival over the succeeding years, which is consistent with the advancement in systemic therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Oncologic safety of postmastectomy breast reconstruction in young women with breast cancer is not well-defined, especially in the setting of neoadjuvant chemotherapy (NACT). We retrospectively compared the oncologic outcomes following nipple-sparing (NSM)/skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) and conventional mastectomy (CM) alone in young breast cancer patients after NACT. Methods: A total of 1266 women with primary breast cancer who underwent NACT followed by total mastectomy with or without IBR were reviewed. Of these, only young patients (age ≤ 40 years at diagnosis) were included in the outcome analysis (n = 375). After propensity score-matching by clinical T and N stage, molecular subtype, response to NACT, and adjuvant radiotherapy status, 228 patients were 1:1 matched, comprising balanced IBR group (with NSM/SSM) and CM-alone group. Results: The 5-year locoregional recurrence-free, disease-free, distant metastasis (DM)-free, and breast cancer-specific survival (BCSS) rates for the entire cohort of young patients were 83.4%, 65.3%, 71.7%, and 85.4%, respectively. Locoregional recurrence rates between the matched groups were similar (14% vs. 15.8%; p = 0.710); however, IBR group had significantly lower DM rate (27.2% vs. 40.4%; p = 0.036) and breast cancer mortality (14.9% vs. 27.2%; p = 0.023) than CM-alone group. IBR group showed significantly improved 5-year DM-free survival (74.1% vs. 62.6%; p = 0.043) and BCSS (89.1% vs. 77.6%; p = 0.048) rates than CM-alone group. Conclusions: Our results indicated that IBR with NSM/SSM does not negatively affect long-term oncologic outcomes compared to CM alone in young women with breast cancer receiving NACT. [ABSTRACT FROM AUTHOR]

Purpose: A large proportion of patients with breast cancer who had mastectomy had undergone breast reconstruction with implants or autologous flaps. However, only a few studies have compared the breast cancer outcomes between the implant-based reconstruction (IBR) and autologous flap reconstruction (AFR). In this study, we retrospectively compared the local recurrence rates, distant metastasis rates, and survival outcomes between immediate IBR and AFR. Methods: A total of 1530 patients with primary breast cancer who underwent IBR or AFR with nipple-/skin-sparing mastectomy were included. Patients who underwent neoadjuvant systemic therapy were excluded from the study. After propensity score matching by age at diagnosis, T stage, N stage, molecular subtype, mastectomy type, adjuvant radiotherapy status, and follow-up period, 938 patients were 1:1 matched, comprising the well-balanced IBR and AFR groups. Locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were compared between the matched groups. Results: After matching, the median follow-up periods were 68 months and 71 months for the IBR and AFR groups, respectively. No significant differences were observed between the IBR and AFR groups regarding the local recurrence (7.2% vs. 5.1%; P = 0.175), regional recurrence (2.1% vs. 1.5%; P = 0.463), or distant metastasis (3.2% vs. 3.2%; P = 1.000) rates. Moreover, no significant difference was observed between the IBR and AFR groups in the LRRFS (hazard ratio, 0.691; 95% CI, 0.433–1.102; P = 0.118), DFS (hazard ratio, 0.709; 95% CI, 0.468–1.076; P = 0.104), DMFS (hazard ratio, 1.006; 95% CI, 0.491–2.059; P = 0.987), or BCSS (hazard ratio, 0.445; 95% CI, 0.111–1.786; P = 0.659). Conclusion: In this propensity score-matched analysis of oncologic outcomes in patients with primary breast cancer who underwent immediate breast reconstruction with nipple-/skin-sparing mastectomy, no significant differences were observed between the IBR and AFR groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: This study was undertaken to investigate the role of postoperative radiotherapy (PORT) including post‐breast conserving radiotherapy (PBCRT) and post‐mastectomy radiotherapy (PMRT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR). Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence‐free survival (LRRFS) and distant progression‐free survival (DPFS). Results: At a median follow‐up of 48.9 months (range, 3.5‐183.4 months), the median OS was 54.9 months (range, 5.3‐185.9 months) with a 5 year OS rate of 59.6%. Lower clinical T stage, Luminal A or B type tumors and PBCRT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. In multivariate analysis for LRRFS, the PBCRT arm demonstrated significant superiority compared to the No PORT arm. A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. PBCRT arm demonstrated significantly superior LRRFS of 100% while PMRT and No PORT arm demonstrated 81.5% and 84.0%, respectively Conclusions: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT, especially PBCRT was predictive of LRRFS, suggesting that patients may benefit from this treatment. [ABSTRACT FROM AUTHOR]

Background: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. Methods: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. Results: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392–1.707, p < 0.001) and 1.405 (95% CI 1.183–1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476–2.328, p < 0.001) and 1.807 (95% CI 1.186–2.752, p = 0.006), respectively. Conclusions: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: A 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. Methods: Overall, 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. Results: After 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. Conclusions: A 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. [ABSTRACT FROM AUTHOR]

Background: Few data are available on the risk factors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NACT) and immediate breast reconstruction (IBR) in breast cancer. Herein, we evaluated the factors predicting LRR in a large series of patients who underwent either nipple- (NSM) or skin-sparing mastectomy (SSM) with IBR after NACT. Methods: We retrospectively analyzed 609 breast cancer patients who underwent NACT and NSM/SSM with IBR between February 2010 and June 2017. Factors associated with an increased risk of LRR were analyzed by univariate (chi-square or Fisher's exact test) and multivariate (Cox proportional hazard regression model) analyses. Results: During a median follow-up of 63 months, LRR as the first event occurred in 73 patients, and the 5-year cumulative LRR rate was 10.8%. Multivariate analysis revealed post-NACT Ki67 ≥ 10% [hazard ratio (HR), 2.208; 95% confidence interval (CI), 1.295-3.765; P = 0.004], high tumor grade (HR, 1.738; 95% CI, 1.038-2.908; P = 0.035), and presence of lymphovascular invasion (LVI) (HR, 1.725; 95% CI, 1.039-2.864; P = 0.035) as independently associated with increased LRR risk. The 10-year LRR rate was 8.5% for patients with none of the three associated risk factors, 11.6% with one factor, 25.1% with two factors, and 33.7% with all three factors (P < 0.001). Conclusions: Post-NACT Ki67 ≥ 10%, high tumor grade, and presence of LVI are independently associated with an increased risk of developing LRR after NACT and NSM/SSM with IBR. Future prospective trials are warranted to decrease the risk of LRR in patients with associated risk factors. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1–3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC). Method: We retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1–4, cN0–3, cM0 breast cancer at the time of diagnosis and 1–3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n = 188) and ALND (n = 295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups. Result: At a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.43–2.05, p = 0.876) and 5-year overall survival (97.7% vs. 97.3%, HR = 1.65, 95% CI = 0.58–4.65, p = 0.347) between the two groups. Conclusion: Our analysis suggests that SLNB alone may be a possible option for patients with 1–3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival. [ABSTRACT FROM AUTHOR]

Background: Although the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea. Methods: A nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan–Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model. Results: Between 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person–years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged ≥60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185–11.613], 50–59 years (HR, 4.343; 95% CI, 2.122–8.891), and 40–49 years (HR, 2.121; 95% CI, 1.068–4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person–years (PY); HR, 12.460; 95% CI, 2.698–57.522] and aged 40–49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966–18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more. Conclusion: Young breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether the outcome to neoadjuvant chemotherapy (NAC) can be predicted by analyzing p53 expression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients. Methods: We retrospectively reviewed 594 patients diagnosed with stage I–III HR-positive, HER2-negative breast cancer, and treated with NAC at the Asan Medical Center between 2008 and 2014. Expression of p53 was assessed, and overall survival (OS) and breast cancer-specific survival (BCSS) were investigated and compared between groups. Results: At a median follow-up period of 69.8 months, OS and BCSS were higher in the p53-negative (p53(−)) group than in the p53-positive (p53(+)) group. Five-year OS was 95.4% in the p53(−) and 92.1% in the p53(+) group (p = 0.005). BCSS was 96.2% in the p53(−) group and 93% in the p53(+) group (p = 0.008). Conclusion: High expression of immunohistochemically detected p53 was strongly and significantly associated with decreased OS and BCSS than low p53 expression, suggesting that p53 may be a powerful prognostic factor in HR-positive, HER2-negative breast cancer patients receiving NAC. [ABSTRACT FROM AUTHOR]

Purpose: We compared oncologic outcomes between breast cancer patients who underwent immediate implant-based breast reconstruction (IBBR) and those who underwent autologous flap reconstruction (AFR) after neoadjuvant chemotherapy (NACT). Methods: The study group comprised 536 patients with primary breast cancer who underwent NACT followed by immediate IBBR or AFR. After propensity score matching, 138 patients in the IBBR group and 276 patients in the AFR group were selected for comparisons of locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS). Results: No significant differences were observed between the matched groups in locoregional recurrence rates (IBBR vs. AFR: 12.3% vs. 12%; P = 0.915) and distant metastasis (13% vs. 17%; P = 0.293). There was also no significant difference between the groups in LRRFS (P = 0.956), DFS (P = 0.606), DMFS (P = 0.283), or BCSS (P = 0.121). The 5- and 10-year LRRFS rates were 87.6% and 85.9% in the IBBR group, and 87.7% and 86.1% in the AFR group; the 5- and 10-year DFS rates were 79% and 77.5% in the IBBR group, and 77% and 75% in the AFR group; the 5- and 10-year DMFS rates were 85.9% and 85.9% in the IBBR group, and 83.2% and 81.8% in the AFR group; and the 5- and 10-year BCSS rates were 97.8% and 91.3% in the IBBR group, and 91.8% and 86% in the AFR group, respectively. Conclusions: In this propensity score-matched analysis of oncologic outcomes in breast cancer patients who underwent immediate reconstruction after NACT, no significant differences were observed between the IBBR and AFR groups. [ABSTRACT FROM AUTHOR]

Survival of breast cancer patients has improved, and treatment-related changes regarding metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivors. We sought to compare metabolic profile changes and the neutrophil-to-lymphocyte ratio (NLR) between patients undergoing neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) 3 years after the treatment. In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR. The mean age of patients was 42 years. The changes in BMI, serum glucose, and TC during NST and after 3 years were significantly different between NCT and NET. The proportion of overweight + obese group and the mean BMI were significantly increased during NCT (26.6% to 37.5%, 22.84 kg/m2 to 23.87 kg/m2, p < 0.05), and these attributes found to have normalized at the 3-year follow-up. In the NET group, BMI changes were not observed (p > 0.05, all). There were no differences in changes over time among in the Hypertension group during NCT and NET (p = 0.96). The mean value of serum TC and fasting glucose significantly increased (< 0.05, both) during NCT and decreased 3 years after NCT (p < 0.05); however, no significant changes were observed in the NET group. The NLR was increased from 1.83 to 3.18 after NCT (p < 0.05) and decreased from 1.98 to 1.43 (p < 0.05) after NET. Compared with minimal metabolic effect of NET, NCT worsens metabolic profiles, which were recovered over 3 years. The NLR was increased after NCT but decreased after NET. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prognosis of breast cancer patients who received neoadjuvant chemotherapy and underwent sentinel lymph node biopsy (SLNB) alone as axillary surgery regardless of their clinical and pathological lymph node status. We reviewed the records of 1,795 patients from Asan Medical Center who were diagnosed with stage I–III breast cancer and received neoadjuvant chemotherapy during 2003–2014. We selected 760 patients who underwent SLNB alone as axillary surgery and divided these patients into four groups according to their clinical lymph node (cN) and pathological lymph node (pN) status: cN(-)pN(-) (n = 377), cN(-)pN(+) (n = 33), cN(+)pN(-) (n = 242), and cN(+)pN(+) (n = 108). We then compared axillary lymph node recurrence, locoregional recurrence (LRR), distant metastasis-free survival (DMFS), and overall survival (OS) among the four groups using Kaplan–Meier analysis. We compared prognosis between the cN(-)pN(-) and cN(+)pN(-) groups to determine whether SLNB alone is an adequate treatment modality even in patients with cN positive pathology before neoadjuvant therapy but SLNB-negative pathology after NAC. The 5-year axillary recurrence rates in the cN(-)pN(-) and cN(+)pN(-) groups were 1.4% and 2.9%, respectively, and there was no significant difference between the two groups (p = 0.152). The axillary recurrence and LRR rates were significantly different among the four groups, with the pN-negative groups (cN[–]pN[–], cN[+]pN[–]) showing lower recurrence rates. DMFS and OS were also significantly different among the four groups, with the cN negative groups (cN[–]pN[–], cN[–]pN[+]) showing improved survival rates. Our study findings suggest that SLNB alone was associated with lower LRR rates even in patients with cN positive pathology before neoadjuvant therapy but cN negative pathology after SLNB. Moreover, recurrence and survival rates differ significantly according to clinical and pathological lymph node status. [ABSTRACT FROM AUTHOR]

Background: In patients with hormone receptor-positive (HR+)/premenopausal breast cancer, luteinizing hormone-releasing hormone analogs (LHRHas) are used as standard endocrine treatment. Based on previous clinical studies, 1-month formulations are recommended in most breast cancer treatment guidelines, but long-acting formulations facilitate reductions in side effects and patient discomfort caused by frequent administration. However, few efficacy studies have been conducted on 6-month formulations. Therefore, this study aimed to evaluate the efficacy of 6-month formulations of LHRHas. Methods: This retrospective study was conducted from January 2018 to December 2019 and involved premenopausal patients with HR+ breast cancer administered 6-month LHRHas as adjuvant treatment after surgery, and those previously administered chemotherapy or other LHRHa types were excluded. Patients' estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured before surgery, and their E2 levels were also measured at 3, 6, 12, 18, and 24 months at periodic postsurgical examinations. Results: A total of 228 patients were included, and the median patient age was 44 (range, 25–54) years. The mean serum E2 and FSH levels before surgery were 69.7 (range, 4–683) pg/mL and 7.3 (range, 0.4–88.9) mIU/mL, respectively, whereas the mean serum E2 level monitored at intervals during the 6-month LHRHa administration was 5.5 (range, 4.0–52) pg/mL. No women menstruated during the follow-up period after the LHRHas administration, and the E2 levels were less than 30 pg/mL in all patients except one. Conclusions: The 6-month LHRHa formulation adequately suppressed ovarian function in premenopausal patients with HR+ breast cancer. This indicates that long-acting LHRHas can be effectively used for patient convenience and that there is high compliance with long-term use. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We used 3D printed-breast surgical guides (3DP-BSG) to designate the original tumor area from the pre-treatment magnetic resonance imaging (MRI) during breast-conserving surgery (BCS) in breast cancer patients who received neoadjuvant systemic therapy (NST). Targeting the original tumor area in such patients using conventional localization techniques is difficult. For precise BCS, a method that marks the tumor area found on MRI directly to the breast is needed. In this prospective study, patients were enrolled for BCS after receiving NST. Partial resection was performed using a prone/supine MRI-based 3DP-BSG. Frozen biopsies were analyzed to confirm clear tumor margins. The tumor characteristics, pathologic results, resection margins, and the distance between the tumor and margin were analyzed. Thirty-nine patients were enrolled with 3DP-BSG for BCS. The median nearest distance between the tumor and the resection margin was 3.9 cm (range 1.2–7.8 cm). Frozen sections showed positive margins in 4/39 (10.3%) patients. Three had invasive cancers, and one had carcinoma in situ; all underwent additional resection. Final pathology revealed clear margins. After 3-year surveillance, 3/39 patients had recurrent breast cancer. With 3DP-BSG for BCS in breast cancer patients receiving NST, the original tumor area can be identified and marked directly on the breast, which is useful for surgery. Trial Registration: Clinical Research Information Service (CRIS) Identifier Number: KCT0002272. First registration number and date: No. 1 (27/04/2016). [ABSTRACT FROM AUTHOR]

To facilitate precise tumor resection at the time of breast-conserving surgery (BCS), we developed and implemented a magnetic resonance imaging (MRI)-based three-dimensional-printed (3DP) breast surgical guide (BSG). This prospective cohort study was conducted at a single institution from July 2017 to February 2019 on women with breast cancer who underwent partial breast resection using patient-specific 3DP BSGs. Eighty-eight patients with invasive cancer were enrolled, of whom 1 patient had bilateral breast cancer. The mean size of the tumor long-axis on MRI before surgery was 2.8 ± 0.9 cm, and multiple tumors were observed in 34 patients. In 16 cases (18.0%), the resection margin was tumor-positive according to intraoperative frozen biopsy; all of these tumors were ductal carcinoma in situ and were re-excised intraoperatively. In 93.3% of the cases, the resection margin was tumor-free in the permanent pathology. The mean pathological tumor size was 1.7 ± 1.0 cm, and the mean distance from the tumor to the border was 1.5 ± 1.0 cm. This exploratory study showed that the tumor area on the MRI could be directly displayed on the breast when using a 3DP BSG for BCS, thereby allowing precise surgery and safe tumor removal. Trial Registration Clinical Research Information Service (CRIS) Identifier (No. KCT0002375, KCT0003043). [ABSTRACT FROM AUTHOR]

Background: Prostaglandin is one of the key metabolites for inflammation-related carcinogenesis. Despite the microRNA-155 is implicated in various types of cancers, it's function in prostaglandin metabolism is largely unknown. Methods: A targeted profiling of eicosanoids including prostaglandin, leukotriene and thromboxanes was performed in miR-155 deficient breast tumors and cancer cells. The molecular mechanism of miR-155-mediated prostaglandin reprogramming was investigated in primary and cancer cell lines, by analyzing key enzymes responsible for the prostaglandin production. Results: We found miR-155-deficient breast tumors, plasma of tumor-bearing mouse and cancer cells show altered prostaglandin level, especially for the prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2). Subsequent analysis in primary cancer cells, 20 triple-negative breast cancer (TNBC) specimens and breast cancer cell lines with miR-155 knockdown consistently showed a positive correlation between miR-155 level and PGE2/PGD2 ratio. Mechanistically, we reveal the miR-155 reprograms the prostaglandin metabolism by up-regulating PGE2-producing enzymes PTGES/PTGES2 while down-regulating PGD2-producing enzyme PTGDS. Further, we show the up-regulation of PTGES2 is driven by miR-155-cMYC axis, whereas PTGES is transactivated by miR-155-KLF4. Thus, miR-155 hires dual-regulatory mode for the metabolic enzyme expression to reprogram the PGE2/PGD2 balance. Lastly, we show the miR-155-driven cellular proliferation is restored by the siRNA of PTGES1/2, of which expression also significantly correlates with breast cancer patients' survival. Conclusions: Considering clinical trials targeting PGE2 production largely have focused on the inhibition of Cox1 or Cox2 that showed cardiac toxicity, our data suggest an alternative way for suppressing PGE2 production via the inhibition of miR-155. As the antagomiR of miR-155 (MRG-106) underwent a phase-1 clinical trial, its effect should be considered and analyzed in prostaglandin metabolism in tumor. [ABSTRACT FROM AUTHOR]

Background & aims: Progranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumors (GISTs) with regard to PGRN expression. Methods: A retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression. Results: Fifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33–79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p<0.001). Multivariate analysis showed that high PGRN expression and old age (>60 years) were independent prognostic factors for poor RFS. Conclusions: High PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection. [ABSTRACT FROM AUTHOR]

Purpose: This 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). Methods: We 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. Results: We 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. Conclusions: No 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. [ABSTRACT FROM AUTHOR]

Purpose: Restricted shoulder mobility is a major upper extremity dysfunction associated with lower quality of life and disability after breast cancer surgery. We hypothesized that a poloxamer and sodium alginate mixture (Guardix-SG®) applied after axillary lymph node dissection (ALND) would significantly improve shoulder range of motion (ROM) in patients with breast cancer. Methods: We conducted a double-blind, randomized, prospective study to evaluate the clinical efficacy and safety of Guardix-SG® for the prevention of upper extremity dysfunction after ALND. The primary outcome measure was shoulder ROM at baseline (T0) and 3 (T1), 6 (T2), and 12 months (T3) after surgery. Secondary outcome measures were the Disabilities of the Arm, Shoulder, and Hand score(DASH), pain associated with movement, which was assessed using a numeric rating scale, and lymphedema assessed using body composition analyzer. Results: A total of 83 women with breast cancer were randomly assigned to either the Guardix-SG® group or the control group. In the Guardix-SG® group (n = 37), Guardix-SG® was applied to the axillary region after ALND. In the control group (n = 46), ALND was performed without using Guardix-SG®. Comparing ROM for shoulder flexion before surgery (178.2°) and 12 months after surgery (172.3°), that was restored 12 months after surgery in the Guardix-SG® group, and there was no statistically significant difference between that at before surgery and 12 months after surgery (p = 0.182). No adverse effect was observed in either group. Conclusions: The results of this study have shown that Guardix-SG® help improve shoulder ROM without causing adverse effects in patients who underwent breast cancer surgery. However, there was no statistically significant difference from the control group. A further large-scale study is needed to obtain a more conclusive conclusion. Trial registration: CRISKCT0003386; https://cris.nih.go.kr (20181207) [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options. Methods: The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice. Results: In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line. Conclusion: For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC. [ABSTRACT FROM AUTHOR]