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The lifetime risk of breast and ovarian cancer increases substantially for individuals with mutations in BRCA1/2. The evidence indicates that BRCA1/2 mutation carriers benefit from early cancer detection and prevention strategies. However, data on the patterns of risk-reducing interventions are lacking. This study investigated the patterns of surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. A cohort of unaffected BRCA1/2 mutation carriers was identified from the Korean Hereditary Breast cAncer (KOHBRA) study database, and a telephone survey was conducted. The survey included questions on the incidence of new cancers, patterns of cancer (breast, ovarian, prostate, other) surveillance, chemoprevention, risk-reducing surgery, and reasons for participating in risk-reducing strategies. Between November 2016 and November 2020, 192 BRCA1/2 mutation carriers were contacted, of which 83 responded. After excluding 37 responders who refused to participate, 46 participants (15 males, 31 females) were included in the analysis. The mean ± SD follow-up time was 103 ± 17 months (median 107, range 68~154), and the mean ± SD age was 31 ± 8 years. Ten BRCA1/2 mutation carriers developed breast cancer, one developed ovarian cancer, and three developed other cancers. Six BRCA1/2 mutation carriers (19.4%) underwent annual breast cancer surveillance as recommended by guidelines, while none underwent ovarian or prostate cancer surveillance. Three carriers (9.7%) used chemoprevention for breast cancer. Risk-reducing salpingo-oophorectomy was performed on only one BRCA1/2 mutation carrier. The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort’s relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed.

Abstract Background Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients. Methods In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels. Results The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age ( 90 days, HR 1.32, 95% CI 1.01–1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation. Conclusion This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy.

Abstract Background This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden. Methods In the multicenter retrospective cohort, 388 individuals with cN1–3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included. Primary outcome was the false-negative rates (FNRs) of SLNB according to the MRI response and subtypes. We defined complete MRI responders as patients who experienced disappearance of suspicious features in the breast and axilla after NAST. Results In the multicenter retrospective cohort, 130 (33.5%) of 388 patients were of cN2-3, and 55 (14.2%) of 388 patients showed complete MRI responses. In hormone receptor-positive HER2− (n = 207), complete and non-complete responders had a high FNRs (31.3% [95% CI 8.6–54.0] and 20.9% [95% CI 14.1–27.6], respectively). However, in HER2+ or TNBC (n = 181), the FNR of complete MRI responders was 0% (95% CI 0–0), whereas that of non-complete responders was 33.3% (95% CI 20.8–45.9). When we validated our findings in the external cohort with HER2+ or TNBC (n = 267), of which 34.2% were cN2-3, the FNRs of complete were 7.1% (95% CI 0–16.7). Conclusions Our findings suggest that SLNB can be a reliable option for nodal status evaluation in selected patients who have responded well to NAST, especially in HER2+ and TNBC patients who show a complete MRI response.

Abstract Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10–20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3–152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P

Abstract Background Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. Methods A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. Results There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160–23.190) in non-pCRw/mic group and 5.970 (1.840–19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130–34.090) in non-pCRw/mic group, 9.120 (2.850–29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230–21.500) without statistical significance (p = 0.486). Conclusions Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Abstract Background Robotic nipple-sparing mastectomy (RNSM) has emerged as a new treatment option for breast cancer and risk-reducing mastectomy (RRM) for women who have a high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that it should only be performed by specialized surgeons, and data on oncologic outcomes and patient-reported outcomes (PROs) are limited. Recently, the United States Food and Drug Administration and several surgeons warned that robotic breast surgery should be performed only by specialized surgeons and recommended that the benefits, risks, and alternatives of all available treatment options be discussed with patients so they can make informed treatment decisions. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and teach this state-of-the-art procedure. We have designed a multicenter prospective cohort study entitled Mastectomy with Reconstruction Including Robot Endoscopic Surgery (MARRES) to report surgical, PRO, and oncologic outcomes. Methods MARRES is a multi-institution cohort study prospectively collecting data from patients undergoing mastectomy and reconstruction. The patient inclusion criteria are adult women older than 19 with breast cancer or a high risk of breast cancer (patients with BRCA1/2, TP53, PALB2 mutations, etc.), who have scheduled therapeutic or RRM and want immediate reconstruction. Surgical outcomes, including pre- and postoperative photos, oncologic outcomes, cost-effectiveness, and PRO, are collected. The primary endpoints are postoperative complication rates within 30 postoperative days and the Clavien-Dindo grade of postoperative complications within 180 postoperative days. The secondary endpoints are 5-year postoperative recurrence-free survival and cancer incidence rate (for those who underwent RRM), patient satisfaction with reconstruction expectations preoperative (baseline) and results within 6 to 12 postoperative months, surgeon satisfaction with postoperative results in 6 postoperative months, and cost-effectiveness of the definitive surgery. Patient recruitment will be completed in April 2025, and the target number of enrolled patients is 2000. Discussion This study will provide evidence about the surgical outcomes, oncologic outcomes, and patient satisfaction with RNSM and endoscopic nipple-sparing mastectomy (NSM), compared with conventional NSM. Trial registration ClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020.

Conclusion: The use of endocrine therapy without surgery could be a potential treatment strategy in patients with DCIS or ADH. Further validation in larger cohorts and in the context of clinical trials is needed.

Aim: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. Methods: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. Results: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. Conclusion: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Abstract Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.

Aim: Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease. Methods: We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR. Results: With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001). Conclusion: We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.

ObjectivePathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR.MethodsThis study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study.ResultsIn total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073).ConclusionResults in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

BackgroundBreast cancer is the most common cancer and the most common cause of cancer death in women. Although survival rates have improved, unmet psychosocial needs remain challenging because the quality of life (QoL) and QoL-related factors change over time. In addition, traditional statistical models have limitations in identifying factors associated with QoL over time, particularly concerning the physical, psychological, economic, spiritual, and social dimensions. ObjectiveThis study aimed to identify patient-centered factors associated with QoL among patients with breast cancer using a machine learning (ML) algorithm to analyze data collected along different survivorship trajectories. MethodsThe study used 2 data sets. The first data set was the cross-sectional survey data from the Breast Cancer Information Grand Round for Survivorship (BIG-S) study, which recruited consecutive breast cancer survivors who visited the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, between 2018 and 2019. The second data set was the longitudinal cohort data from the Beauty Education for Distressed Breast Cancer (BEST) cohort study, which was conducted at 2 university-based cancer hospitals in Seoul, Korea, between 2011 and 2016. QoL was measured using European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 questionnaire. Feature importance was interpreted using Shapley Additive Explanations (SHAP). The final model was selected based on the highest mean area under the receiver operating characteristic curve (AUC). The analyses were performed using the Python 3.7 programming environment (Python Software Foundation). ResultsThe study included 6265 breast cancer survivors in the training data set and 432 patients in the validation set. The mean age was 50.6 (SD 8.66) years and 46.8% (n=2004) had stage 1 cancer. In the training data set, 48.3% (n=3026) of survivors had poor QoL. The study developed ML models for QoL prediction based on 6 algorithms. Performance was good for all survival trajectories: overall (AUC 0.823), baseline (AUC 0.835), within 1 year (AUC 0.860), between 2 and 3 years (AUC 0.808), between 3 and 4 years (AUC 0.820), and between 4 and 5 years (AUC 0.826). Emotional and physical functions were the most important features before surgery and within 1 year after surgery, respectively. Fatigue was the most important feature between 1 and 4 years. Despite the survival period, hopefulness was the most influential feature on QoL. External validation of the models showed good performance with AUCs between 0.770 and 0.862. ConclusionsThe study identified important factors associated with QoL among breast cancer survivors across different survival trajectories. Understanding the changing trends of these factors could help to intervene more precisely and timely, and potentially prevent or alleviate QoL-related issues for patients. The good performance of our ML models in both training and external validation sets suggests the potential use of this approach in identifying patient-centered factors and improving survivorship care.

Abstract Background Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients. Methods We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort. Results From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p

Due to the rarity of primary angiosarcoma of the breast, optimal management is based on expert opinion. The aim of this study was to review all primary angiosarcomas of the breast obtained from a single center in terms of clinicopathologic characteristics, treatment, and survival outcomes. From 1997 to 2020, 15 patients with primary angiosarcoma of the breast underwent either mastectomy or wide excision. We analyzed the clinicopathologic data to assess disease-free survival and overall survival. Fifteen women with primary angiosarcoma of the breast were identified. The mean age at diagnosis was 33 years (range: 14–63 years). The overall mean tumor size was 7.7 cm (range 3.5–20 cm). Upon histological grading, there were three cases of low grade, five intermediate grade, six high grade, and one unidentified grade. The five-year disease-free survival rate was 24.4%, and the five-year survival rate was 37.2%. The survival rate of the low-grade patient group was statistically higher than that of the intermediate- or high-grade patient groups (p = 0.024). Primary angiosarcoma of the breast is a rare aggressive tumor characterized by high grade and poor outcome. Histologic grade appears to be a reliable predictor of survival. There are no standard treatment guidelines; thus, optimal R0 surgical resection remains the best approach. The roles of neoadjuvant, adjuvant chemotherapy, and radiotherapy remain unclear.

Abstract 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.

PurposeThe incidence of early tumor detection is increasing due to popularization of breast cancer screening and the development of imaging techniques. Thus, suitable preoperative localization is required for proper diagnosis and treatment of non-palpable breast lesions. The purpose of this study was to evaluate the efficacy and safety of indocyanine green (ICG)-hyaluronic acid (HA) mixture for lesion localization compared to activated charcoal.MethodsThis was a multicenter, randomized, open-label, parallel phase 3 clinical trial performed at four centers in Korea. Female patients scheduled for surgery to remove non-palpable breast lesions were enrolled. One hundred and nine patients were randomly assigned to a control group (activated charcoal: 0.3. – 1 mL) or a study group (ICG-HA mixture, 0.2 mL) for the localization of a breast lesion. The primary endpoint was the accuracy of resection. Secondary endpoints included the technical success rate, histopathological accuracy, skin pigmentation rate, and adverse event rate.ResultsA total of 104 patients were eligible for per-protocol analysis (control group, n = 51; study group, n = 53). The accuracy of resection in the study group was not inferior to that of the control group (90.57% vs. 98.04%, 95% confidence interval (CI): -2.31 – 18.91, p = 0.21). There was no statistically significant difference in technical success rate between the two groups (marking on breast skin: p = 0.11, marking on the excised specimen: p = 0.12). However, there were statistically significant differences in histopathological accuracy (0.26 ± 0.13 vs. 0.33 ± 0.17, p = 0.01) and skin pigmentation rate (0.00% vs. 30.77%, p< 0.01). Adverse events were not reported in either group.ConclusionsWhen localization was performed using ICG-HA, the accuracy of resection was not inferior to that of activated charcoal. However, skin pigmentation rate was significantly lower. In conclusion, ICG-HA is effective and safe for localizing of non-palpable breast lesions.

Abstract Robotic nipple-sparing mastectomy (RNSM) provides better cosmetic outcomes and improves the quality of life of women with breast cancer. However, this has not been widely adapted due to the lack of well-structured training programs. The present study aimed to report the establishment of cadaveric and animal skill laboratory training programs for RNSM and the participants’ perception on the training programs. We performed 24 RNSMs using 11 cadavers and one porcine model. Then, the skill laboratory characteristics were reviewed. Five trainers and 10 trainees participated in the programs. The first four cadaveric RNSMs with latissimus dorsi flaps and implants were performed using the da Vinci Si® system. We performed 14 and six RNSMs using the Xi® and SP® systems, respectively. The scores for questionnaires on the satisfaction with the training consisted of the trainees’ perceived goals in attending the course, teaching/learning environment, and teaching staff performance. The scores were excellent. Cadaveric or porcine RNSM skill laboratory training may be essential programs that can provide safe and efficient training.

Abstract We hypothesized that a deep-learning algorithm using HE images might be capable of predicting the benefits of adjuvant chemotherapy in cancer patients. HE slides were retrospectively collected from 1343 de-identified breast cancer patients at the Samsung Medical Center and used to develop the Lunit SCOPE algorithm. Lunit SCOPE was trained to predict the recurrence using the 21-gene assay (Oncotype DX) and histological parameters. The risk prediction model predicted the Oncotype DX score > 25 and the recurrence survival of the prognosis validation cohort and TCGA cohorts. The most important predictive variable was the mitotic cells in the cancer epithelium. Of the 363 patients who did not receive adjuvant therapy, 104 predicted high risk had a significantly lower survival rate. The top-300 genes highly correlated with the predicted risk were enriched for cell cycle, nuclear division, and cell division. From the Oncotype DX genes, the predicted risk was positively correlated with proliferation-associated genes and negatively correlated with prognostic genes from the estrogen category. An integrative analysis using Lunit SCOPE predicted the risk of cancer recurrence and the early-stage hormone receptor-positive breast cancer patients who would benefit from adjuvant chemotherapy.

Abstract Decision to undergo risk-reducing mastectomy (RRM) needs to consider several factors, including patient’s preference, surgeon’s preference, family history, and genetic predisposition. The aim of this study was to examine whether preoperative diagnosis of BRCA1/2 mutation status could influence surgical decision-making in newly diagnosed breast cancer patients. We retrospectively reviewed ipsilateral breast cancer patients with BRCA1/2 mutation who underwent primary surgery between January 2008 and November 2019 at a single institution in Korea. Of 344 eligible patients, 140 (40.7%) patients were aware of their mutation status ‘prior to surgery’, while 204 (59.3%) did not. Contralateral RRM rate was significantly higher in the group with BRCA1/2 mutation status identified ‘prior to surgery’ compared to the group with mutation status identified ‘after surgery’ [45.0% (63/140) vs. 2.0% (4/204)] (p

Purpose: This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC). Materials and Methods: We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45-65 Gy in 15--30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan--Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model. Results: During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis- free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00-3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57-14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI. Conclusion: In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients. [ABSTRACT FROM AUTHOR]

Abstract Background Increasing rates of breast cancer screening have been associated with an increasing frequency of non-palpable breast lesions detection. Preoperative breast lesion localization is essential for optimizing excision accuracy. This study aimed to evaluate the efficacy and safety of indocyanine green (ICG) hyaluronic acid injection as a novel mixture for localization. Methods We performed a prospective clinical trial with female patients who underwent surgery for non-palpable breast lesions. All patients were sequentially assigned to the control group (localization with activated charcoal), Test Group 1 (ICG-hyaluronic acid mixture 0.1 mL), or Test Group 2 (ICG-hyaluronic acid mixture 0.2 mL) by 1:1:1 ratio. Results A total of 44 patients were eligible for this study (Control Group = 14, Test Group 1 = 15, Test Group 2 = 15 patients). Fibroadenoma (n = 17, 38.6%) accounted for the largest proportion of diagnoses, and five patients (11.4%) were diagnosed with malignancies. There were no statistically significant differences in baseline characteristics among the three groups. The marking rate was over 86% in all groups, with no significant intergroup differences. Skin pigmentation was only observed in the control group. The mean accuracy of resection (the greatest diameter of the excised specimen divided by the greatest diameter of the preoperative lesion as observed using ultrasonography, with values closer to 1 reflecting a higher accuracy) was 3.7 in the control group, 2.2 in Test Group 1, and 2.1 in Test Group 2 (p = 0.037 between Controls and Test Group 1, p = 0.744 between Test Group 1 and Test Group 2, and p = 0.026 between Controls and Test Group 2). Conclusion ICG-hyaluronic acid injection is a novel method that was shown to accurately localize non-palpable breast lesions and was associated with no skin pigmentation. Further research is required to apply this method to malignant breast lesions. Trial registration “A Multicenter Open-label, Parallel, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of LuminoMark™ Inj. (Conc. for Fluorescence) Localization in Patients with Non-palpable Breast Lesions” was prospectively registered as a trial (ClinicalTrials. gov Identifier: NCT03743259, date of registration: May 29, 2018, https://clinicaltrials.gov/ct2/show/NCT03743259 )

Abstract Background Immediate breast reconstruction with tissue expander in breast cancer patients who were expected to receive adjuvant therapy, such as chemotherapy or radiotherapy, has been a topic of debate. Postoperative complications from tissue expander procedures can delay the timing of adjuvant treatment and subsequently increase the probability of recurrence. The purpose of this study was to identify the impact of chemotherapy and radiotherapy on postoperative complications in patients who underwent immediate reconstruction (IR) using tissue expander. Methods We conducted a retrospective study of 1081 breast cancer patients who underwent mastectomy and IR using tissue expander insertion between 2012 and 2017 in Samsung Medical Center. The patients were divided into two groups based on complications (complication group vs. no complication group). Complication group was regarded to have surgical removal or conservative treatment based on clinical findings such as infection, capsular contracture, seroma, hematoma, rupture, malposition, tissue viability, or cosmetic problem. The complication group had 59 patients (5.5%) and the no complication group had 1022 patients (94.5%). Results In univariate analysis, adjuvant radiotherapy and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, only higher pathologic N stage was significantly associated with postoperative complications (p

BackgroundEndocrine therapy is administered to hormone-positive breast cancer patients to prevent distant metastasis. It is important to evaluate the risk of recurrence and to determine which patients are viable candidates for such treatment because hormone therapy has side effects that can include postmenopausal symptoms. The Clinical Treatment Score post–five years (CTS5), a simple tool for identifying candidates for endocrine therapy, was recently introduced; however, CTS5 only has been applied in validation studies with postmenopausal women. We aimed to validate CTS5 among premenopausal breast cancer patients.MethodsWe identified patients treated between 1994 and 2014 at Samsung Medical Center in Seoul, Korea, and followed their treatment outcomes for more than 60 months after surgery using clinicopathologic parameters. According to menopausal status, we divided the study population into two groups: pre- and postmenopausal women. After calculating CTS5 values based on some parameters, we stratified the rate of late distant recurrence (DR) and analyzed the correlation between CTS5 value and late DR by risk.ResultsAmong 16,904 patients treated surgically for breast cancer, 2,605 with hormone receptor–positive breast cancer who received endocrine therapy were included. Of these, 1,749 (67.14%) patients were premenopausal women, and the median age was 44.00 years. When categorizing study participants according to CTS5-related risk for late DR, 86.79% were categorized as low risk, 5.95% were categorized as intermediate risk, and 7.26% were categorized as high risk. The annual rate of DR was 1.41% for those in the present study and was similar between pre- and postmenopausal participants (1.40 vs. 1.42). Distant metastasis-free survival was not different between the two groups (hazard ratio: 0.817, 95% confidence interval [CI]: 0.547–1.221). The area under the receiver operating characteristic curve at 10 years for premenopausal and postmenopausal patients was 61.75 (95% CI: 52.97–70.53) and 72.71 (95% CIs: 63.30–82.12), respectively.ConclusionsAlthough CTS5 was able to predict late DR, it should be applied with caution in premenopausal women. A CTS5 calculator for premenopausal women might be needed to not underestimate the risk of recurrence in Korea.

BackgroundThe prognostic or predictive value of commonly used multigene assays in young patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer is unclear. In this study, we assessed the prognostic value of the GenesWell BCT assay according to age group.MethodsWe identified patients with pN0-1, HR+/HER2− breast cancer in a prospective cohort of women who underwent surgery between 2005 and 2017. The GenesWell BCT assay was performed on tissue samples from selected patients. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the risk groups assigned by the BCT score.ResultsA total of 712 patients were eligible for analysis. The median follow-up time was 7.47 years. The BCT score was prognostic in patients aged ≤50 years (n = 404) and those aged >50 years (n = 308). In both age groups, the 10-year DMFS and DFS rates for patients classified as high risk by the BCT score were significantly lower than those for patients classified as low risk. A multivariate analysis revealed that the BCT score was an independent prognostic factor for DFS in patients aged ≤50 years (hazard ratio, 1.28; 95% CI, 1.05–1.56; P = 0.015), as well as those aged >50 years.ConclusionThe BCT score could be used to identify low-risk patients who will not benefit from adjuvant chemotherapy to treat HR+/HER2− early breast cancer regardless of age. A further prospective study to assess the prognostic and predictive value of the BCT score is required.

Background: While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor (ER)-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to antihormone therapy. The authors investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial. Materials and methods: The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor-positive breast cancer after chemotherapy. The authors updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging-Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference. Results: The authors evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups [TAM-only group (106/476 (22.3%)) vs. TAM +OFS group (89/468 (19.0%)); P=0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM +OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR: 0.37; 95% CI: 0.16-0.85; P=0.019), but not in the TAM-only group (Pinteraction=0.039). MDR-positive patients who received TAM+ OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR: 0.30; 95% CI: 0.13-0.70; P= 0.005). Conclusion: Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+ OFS group. [ABSTRACT FROM AUTHOR]

Purpose Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant. Materials and Methods This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants were reviewed. Results A younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All seven cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected. Conclusion We suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1. [ABSTRACT FROM AUTHOR]

Purpose Little is known about the impact of financial toxicity in disease-free breast cancer survivors. We aim to validate the COmprehensive Score for financial Toxicity in Korean (COST-K) and evaluate financial toxicity among disease-free breast cancer survivors. Materials and Methods We conducted linguistic validation following a standardized methodology recommended by Functional Assessment of Chronic Illness Therapy multilingual translation (FACITtrans). For psychometric validation, we conducted a cross-sectional survey with 4,297 disease-free breast cancer survivors at a tertiary hospital in Seoul, Korea between November 2018 and April 2019. Survivors were asked to complete the COST-K and European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) questionnaires. The test-retest reliability, internal consistency, and validity of the COST-K were assessed using standard scale construction techniques. Results The COST-K demonstrated good internal consistency, with a Cronbach’s α of 0.81. The test-retest analysis revealed an intraclass correlation coefficient of 0.78. The COST-K had moderate correlation (r=–0.60) with the financial difficulty item of the EORTC QLQ-C30 and week correlation with the items on acute and chronic symptom burdens (nausea/vomiting, –0.18; constipation, –0.14; diarrhea, –0.14), showing good convergent and divergent validity. The median COST-K was 27 (range, 0 to 44; mean±standard deivation [SD], 27.1±7.5) and about 30% and 5% of cancer survivors experienced mild and severe financial toxicity, respectively. Younger age, lower education, lower household income was associated with higher financial toxicity. Conclusion The COST-K is a valid and reliable instrument for measuring financial toxicity in disease-free breast cancer survivors. Considering its impact on the health-related quality of life, more studies need to be conducted to evaluate financial toxicity in cancer survivors and design interventions. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. Materials and Methods: The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer-related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. Results: The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. Conclusion: L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P. [ABSTRACT FROM AUTHOR]