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Backgrounds/Aims: Nipple sparing mastectomy (NSM) is popularly performed as this surgical technique is oncological safety and better cosmetic outcomes. Robot assisted NSM (RANSM) is emerging because of its exceptional advantages: hidden incisions, high resolution, wider visualization and ergonomically moving. Although several studies reported that RANSM has shown a short learning curve, there were few reports about learning curve of this cutting-edge surgical technique. In this study, we reported the learning curve and feasibility of RANSM. Methods: A retrospective and prospective study was conducted for women who underwent RANSM with immediate breast reconstruction at Samsung Medical Center from July 2019 to April 2022. All RANSM were performed by a single surgeon. We divided the total cases in half and set up two phases; an early phase (case 1st to 23th) and a late phase (case 24th to 46th). The total operation time, mastectomy time, docking time, pre-console time and console time was defined as the interval between the creation of the skin incision and the end of the reconstructive surgery, the interval between the time of skin incision and the time of the specimen out of the operation field, the interval between the preparation for docking and the end of docking, the interval between the creation of the skin incision and the end of robot docking, and the time spent by a surgeon to operate the console for mastectomy. To evaluate the impact of case experience accumulation on the operation time of RANSM, the cumulative sum (CUSUM) method was used to analyze the learning curve. Clinicopathologic characteristics, perioperative complications, and operation time were collected. Results: Overall, 42 women underwent 46 RANSM procedures conducted. The median patient age was 44.5 years old (26-59 years) and the median breast weight was 338.5 gram (101.4-817 gram). BRCA 1 mutation carriers were 2 patients and BRCA 2 mutation carriers were 3 patients. 5 patients with BRCA 1/2 mutation carriers underwent contralateral risk-reducing RANSM. Clinicopathologic characteristics of patients between the early phase and late phase were summarized in Table 1. There were no significant differences in almost clinicopathologic characteristics. Median time of total operation, mastectomy, docking time, pre-console time, and console time was 344.0 minutes (254.0-480.0 minutes), 238.5 minutes (166-394 minutes), 6.5 minutes (1-25 minutes), 61.5 minutes (29-180 minutes), and 64.5 minutes (33-134 minutes), respectively. Comparing the early phase and the late phase, median total operation time was 357 minutes (273-480 minutes) and 321 minutes (254-459 minutes), (p = 0.067); median mastectomy time was 245 minutes (204-394 minutes) and 229 minutes (166-376 minutes), (p = 0.070); docking time 7.0 minutes (3-25 minutes) and 5.0 minutes (1-20 minutes),(p = 0.093); pre-console time was 70.0 minutes (49-162 minutes) and 54.0 minutes (29-180 minutes),(p = 0.028); console time was 71.0 minutes (40-134 minutes) and 60.0 minutes (33-105 minutes), (p = 0.095). In the learning curve analysis, it took the 21th procedure in RANSM to decrease the breast operation time. Clavien-Dindo grade III postoperative complication was two cases (8.6%, one case was infection and one case was nipple ischemia) in only early phase and none in the late phase. Clavien-Dindo grade II postoperative complication was absent in all phases. Clavien-Dindo grade I postoperative complications were seven cases (30.4%, all cases were nipple crust) in the early phase and one case (4.3%, one case was nipple crust) in the late phase. Nipple ischemia was found in two cases (8.6%) but only one case required nipple excision given in the early phase. Conclusions: It has shown that the breast operation time improved from the 21th procedure of RANSM. RANSM is technically feasible and acceptable with a short learning curve. TABLE 1. Basic characteristics of patients between the early phase and late phase Citation Format: Yeon JIn Kim, Soo Yeon Chung, Byung Joo Chae, Jonghan Yu, Jeong Eon Lee, Jai Min Ryu. Learning curve for Robotic assisted nipple sparing mastectomy: a single institution experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-03.

Purpose Docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist.Materials and Methods We retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020.Results Of 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%).Conclusion Neoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.

Robotic nipple-sparing mastectomy (RNSM) has been developed to reduce conspicuous scar and increase the quality of life in women. This study aimed to evaluate the surgical and oncologic outcomes of RNSM with immediate breast reconstruction (IBR) compared with conventional nipple-sparing mastectomy (CNSM).This international multicenter, pooled analysis of individual patient-level data enrolled a total of 755 procedures in 659 women (609 had breast cancer and 50 underwent risk-reducing mastectomy) who underwent nipple-sparing mastectomy with IBR. Surgical and oncologic outcomes, including 30-days postoperative (POD 30d) complication rate, nipple necrosis rate, grade of Clavien-Dindo classification, disease-free survival, and overall survival, were evaluated. Propensity score-matched analyses were performed to adjust for confounding factors.The median age of both the RNSM and CNSM groups was 45 years. The RNSM group had lower body mass index (BMI) and a higher proportion of benign disease compared with the CNSM group. POD 30d complications and postoperative complication grade III rates were lower in the RNSM group than in the CNSM group (p0.05). The nipple necrosis rate was 2.2% and 7.8% for RNSM and CNSM, respectively (p = 0.002). After propensity score matching, significantly lower rates of POD 30d complications, nipple necrosis, and postoperative complication grade III occurred in the RNSM group than in the CNSM group (all p0.05). Oncologic outcomes were not significantly different between the two groups.RNSM can provide better cosmetic results with favorable surgical and oncologic outcomes for women with early breast cancer or BRCA mutation.

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.

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.

Background: Robot nipple sparing mastectomy (RNSM) has emerged for breast cancer treatment and for risk reducing mastectomy in women who have high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that RNSM are only performed by several specialized surgeons and there is only limited data reporting about the oncologic outcome and patient reported outcome (PRO). Recently, the United States Food and Drug Administration and several surgeons have warned that robot breast surgery should be performed only by specialized surgeons and the benefits, risks, and alternatives of all available treatment options should be discussed with patients to make the most informed treatment decision. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and developing education program this cutting-edge procedure. We designed a multicenter prospective cohort study of Mastectomy with Reconstruction including Robot Endoscopic Surgery (MARRES) to report surgical outcome, PRO, and oncologic outcome. Methods: The MARRES study is a multi-institution cohort study that prospectively collects data from patients undergoing mastectomy and reconstruction. Patients' inclusion criteria are as below; adult women over the age of 19, with breast cancer or high risk of breast cancer (patients with a BRCA1/2 mutation, TP53 mutation, and PALB2 mutation), who scheduled therapeutic or prophylactic mastectomy, and who want immediate reconstruction. Surgical outcomes, oncologic outcomes, cost-effectiveness, and PRO were collected. The primary endpoints were postoperative complication rates in postoperative 30 days and Clavien-Dindo grade of postoperative complications in postoperative 180 days. The secondary endpoints were recurrence free survival in postoperative 5 years, cancer incidence rate in postoperative 5 years for those who underwent risk reducing mastectomy, patient's satisfaction within preoperative 4 weeks and results within postoperative 6 months to 12 months, surgeon's satisfaction about the postoperative results in postoperative 6 months, and cost-effectiveness of the definitive surgery. Patient recruitment will be finished in April 2025 and the goal number of enrolled patients is 2,000. Discussion: This study will provide evidence of the surgical outcome, PRO, and oncologic outcome of RNSM and endoscopic NSM compared to conventional NSM. Trial registration: ClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020. Citation Format: Jeea Lee, Jai Min Ryu, Jee Yeon Lee, Beom Seok Ko, Saebyeol Lee, Joo Heung Kim, Hee Jun Choi, Hyuk-Jae Shin, Young Woo Chang, Hye Yoon Lee, Hong-Kyu Kim, Hyung Seok Park. Mastectomy with reconstruction including robot endoscopic surgery (MARRES): A prospective cohort study of the Korea robot-endoscopy minimal access breast surgery study group (KoREa-BSG) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-12-01.

We provide evidence for the reclassification of theThis study included breast or ovarian cancer patients tested forWe present 10 breast cancer patients and 7 ovarian cancer patients from 15 families identified as havingWe presented clinical evidence for the reclassification of

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.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.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).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.

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 Conclusions This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.

Introduction Adding pertuzumab(P) on trastuzumab(H) with cytotoxic chemotherapy increased pathologic complete response (pCR) of early or locally advanced HER2 positive breast cancer (EBC) with neoadjuvant chemotherapy. Since 63.6% of pCR rate has been reported from TRYPHAENA trial, TCHP regimen has been used as a standard of neoadjuvant treatment regimen for patients with HER2 positive EBC. However, this regimen has profound toxicities in terms of myelosuppression, neurotoxicity, and etc. Furthermore we still need more information on clinical outcomes and toxicities with this regimen. Therefore, we report real world experience of EBC patients treated with neoadjuvant TCHP followed by curative surgery. Methods We retrospectively reviewed electronic medical record of EBC patients who received neoadjuvant TCHP. Information which we gathered included patients’ and tumor characteristics at the time of diagnosis, details of neoadjuvant chemotherapy, pathologic assessment of tumor response to neoadjuvant TCHP and recurrence free survival after curative surgery. pCR was defined as absence of residual invasive cancer on pathologic evaluation of the resected breast specimen and all sampled regional lymph nodes (ypT0/isN0). Results Between February 2016 and August 2019, 447 patients were treated with neoadjuvant TCHP followed by curative surgery. Median age at BC diagnosis was 56. In clinical stage, stage II was 54.6% and 45.4% of stage III and hormone receptor (HR) positive BC was 48.3%. Most commonly reported adverse event(AE) was mucositis (84%) followed by diarrhea (77%). In terms of Grade 3 AE, anorexia(6%), diarrhea(2%) were frequently observed and 9(2%) of febrile neutropenia occurred despite of prophylactic use of peg-filgrastim. Forty percent of patients experienced dose reduction due to AEs. Of 447 patients, 29% of patients underwent total mastectomy and 71% of breast conserving surgery. In terms of clinical outcome, pCR rate was 64%; 77% of HR negative BCs and 50% of HR positive BCs. Among baseline characteristics, high nuclear grade, high histologic grade, HR stats affected to pCR status (Ps Key words: neoadjuvant chemotherapy, HER2+ breast cancer, pertuzumab, pathologic complete response Citation Format: Ji-Yeon Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park. Real Would Evidence (RWE) of neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) in patients with HER2 positive early or locally advanced breast cancer treated Single institutional experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-38.

Background The aim of this study was to examine the accuracy of radiologic complete response (rCR) in predicting pathologic complete response (pCR), and determine whether rCR is a predictor of favorable survival outcomes. Materials and methods We retrospectively reviewed breast cancer patients treated with neoadjuvant chemotherapy (NAC) followed by surgery from September 2007 to June 2016. Breast lesions and axillary nodes were measured by MRI and categorized into either disappeared (breast rCR) or residual disease (breast non-rCR) and either normalized (axillary rCR) or abnormal findings (axillary non-rCR) in the axillary nodes. Correlation between rCR and pCR were compared using Cohen’s Kappa statistics, and the recurrence-free survival (RFS) and overall survival (OS) rates were calculated by the Kaplan-Meier method. Results Out of the 1017 eligible patients, 287 (28.2%) achieved breast pCR, 165 (16.2%) achieved breast rCR, 529 (52.0%) had axillary pCR, and 274 (26.9%) achieved axillary rCR. The correlation between a breast rCR and pCR showed a Cohen’s Kappa value of 0.459, and between axillary rCR and pCR, the value was 0.384. During a median follow-up time of 48.0 months, the 5-year RFS rates were 90.6% for breast rCR, and 69.2% for breast non-rCR. The 5-year RFS rates were 82.3% for axillary rCR, and 68.8% for axillary non-rCR. Patients without breast rCR had a 2.4-fold significant increase in the risk of recurrence (p = 0.004) compared to patients with breast rCR. Conclusion Although rCR correlated with pCR by only moderate to fair degrees, breast rCR was a strong predictor for a favorable RFS outcome.

To examine the association between obesity measured by body mass index (BMI) and waist circumference (WC) according to menopausal status in Korean women. We identified 6,467,388 women, using the Korean National Health Insurance System Cohort. Cox-proportional hazard models were used to generate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for breast cancer risk in relation to BMI and WC. In postmenopausal women, the risk of breast cancer increased with BMI. Compared to women with a BMI of 18.5–23 kg/m two, the risk of invasive breast cancer was lower in patients with BMI

Objective The aim of this study was to present the results of early experience of RANSM. Background Robot-assisted nipple-sparing mastectomy (RANSM) improves cosmetic outcomes over conventional nipple-sparing mastectomy (CNSM). However, data on the feasibility and safety of the RANSM are limited. Methods Patients who underwent RANSM with immediate breast reconstruction (IBR) as part of the Korea Robot-Endoscopy & Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. Clinicopathologic characteristics, perioperative complications, and operation time were collected. Results Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at eight institutions. The median patient age was 45.0 years old (20-66 years), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage I, 11 cases were stage II, and four cases were stage III, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, three patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 11.7 days (5.0-24.0 days). The incision location was the mid-axillary line and the median incision length was 46.3 mm (30.0-60.0 mm). Median total operation time, median total mastectomy time, and median reconstruction time was 322.0 minutes (163.0-796.0 minutes), 190.8 minutes (97.5-325.0 minutes), and 133.6 minutes (45.0-689.0 minutes). Only two cases (2.5%) required re-operation. Nipple ischemia was found in nine cases (10.9%) but only one case (1.2%) required nipple excision given that eight cases (9.7%) resolved spontaneously. Skin ischemia was observed in five cases (6.1%) and only two (2.4%) cases needed skin excision whereas three cases (3.6%) resolved spontaneously. There was no conversion to open surgery or cases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). Conclusion This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.

PurposeRecent 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 MethodsThe 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.ResultsThe 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.ConclusionL1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

Background Triple-negative breast cancer (TNBC) is known to have a higher risk of early recurrence and relatively low risk of late recurrence compared to luminal type breast cancer. Among all subtypes of breast cancer, TNBC is more likely to have BRCA1/2 germline mutation which showed prevalence rate from about 10% to 20% in previous reports. To date, there are only few studies about the effect of BRCA1/2 mutations on the long-term oncologic prognosis in TNBC patients. We analyzed long-term oncologic outcome in unselected TNBC patients according to BRCA1/2 mutations in a comprehensive single institution. Methods Among 11,994 patients who underwent primary breast cancer surgery at Samsung Medical Center (SMC) between June 2008 and January 2016, 1,628 (13.6%) were TNBC patients. Of those, patients with inadequate and unavailable samples at SMC biobank and patients with follow-up duration less than 12 months and who had distant metastasis at presentation were excluded from the study, and 953 patients were enrolled. A retrospective study was conducted and BRCA1/2 genetic testing was done with SMC biobank samples through Next Generation Sequencing (NGS). Results Among 953 unselected TNBC patients, 122 patients (12.8%) had BRCA1/2 mutations: 91 (9.5%) were in BRCA1, and 32 (3.4%) were in BRCA2. One patient had both BRCA1/2 mutations. BRCA1/2 carriers were more likely to have personal history of ovarian cancer (9.0% vs. 0.5%, p < 0.0001), family history of breast cancer and/or ovarian cancer (40.2% vs. 9.4%, p < 0.0001), bilateral breast cancer (4.9% vs. 1.2%, p = 0.0105), and higher nuclear grade (86.0% vs. 74.0%, p = 0.0250). The median follow-up duration was 80.9 months. There were no significant differences in disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) (p = 0.375, 0.268, 0.413, and 0.133, respectively) between BRCA1/2 carriers and non-carriers. However, BRCA1/2 carriers showed significantly worse contralateral breast cancer (CBC)-free survival than non-carriers (p < 0.0001). Sixty and 120-months cumulative recurrence rate were 18.5% and 31.2% for BRCA1/2 carriers versus 19.3% and 22.7% for non-carriers (p = 0.834 and 0.136, respectively). However, cumulative recurrence rate at 150 months showed absolute but not statistically significant difference between BRCA1/2 carriers and non-carriers (36.2% versus 23.5%, p = 0.080). Cumulative CBC recurrence rate on 60, 120- and 150-months estimates were 6.7%, 18.7% and 25.5% for BRCA1/2 carriers versus 1.1%, 2.7% and 5.2% for non-carriers which showed statistically meaningful difference (p = 0.025, 0.006 and 0.018, respectively). Sixty months, 120- and 150-months cumulative expire rate were 11.2%, 15.6% and 27.7% for BRCA1/2 carriers versus 14.3%, 20.7% and 20.7% for non-carriers (p = 0.319, 0.202 and 0.549, respectively). Discussion In this unselected cohort of patients with TNBC, we found 12.8% (122 patients among 953) prevalence of BRCA1/2 mutations. The median follow-up duration was 80.9 months. There was no significant difference in DFS, DMFS, OS and BCSS by BRCA1/2 mutation status in long-term follow up. However, BRCA1/2 carriers showed significantly worse CBC recurrence rate at 60, 120- and 150- months. And also, BRCA1/2 carriers had 12.7% higher risk of recurrence than non-carriers at 150 months, which was not statistically meaningful but showed absolute difference. Among patients with CBC recurrence, 41.3% (12 patients among 29) were BRCA1 carriers, over 85% had TNBC type of recurred CBC and approximately 80% underwent chemotherapy. In conclusion, we demonstrated that CBC recurrence risk is relatively high in TNBC patients with BRCA1 mutation and showed high chance to receive chemotherapy. Therefore, long-term follow up and appropriate genetic counseling, risk assessment should be done properly for BRCA1/2 mutation carriers in TNBC patients. Citation Format: Soo Yeon Chung, Jai Min Ryu, You Jin Jung, Yeon Jin Kim, Hye Jin Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Jeong Eon Lee, Se Kyung Lee, Sung-Won Kim, Eun Young Kim. Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-01.

The GenesWell™ breast cancer test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and human epidermal growth factor-2 negative (HER2-) early breast cancer (BC). The ability of this assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date.Biopsy specimens from HR+/HER2- BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified BCT score was developed and patients classified into high-and low-response groups. A total of 88 patients were available for the BCT score among the 108 eligible patients. The median follow-up duration was 35.9 (7.8-128.5) months.Among them, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or cT2 disease. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%). Among the 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high BCT score group and 9 (18.0%) were in the low BCT score group. Among the 38 patients with stable or progressive disease, 22 (57.9%) were in the high BCT score group and 16 (42.1%) were in the low BCT score group (We demonstrated that the BCT score predicts NACT responsiveness in HR+/HER2- BC with LN metastasis and might help determine whether NACT should be performed. Further studies are required to validate these results.

In two-stage prosthetic breast reconstruction, autologous fat graft (AFG) is often conducted simultaneously with the second-stage operation, which is usually performed shortly after mastectomy. There is a paucity of studies evaluating whether conducting AFG early, with a relatively short interval from the primary operation, is oncologically safe. This study aimed to evaluate potential associations of AFG with breast cancer prognosis, focusing on its timing.Patients with invasive breast cancer who underwent immediate two-stage prosthetic reconstruction following mastectomy between 2011 and 2016 were identified. They were categorized into two groups by whether AFG was performed during the second-stage operation. Cumulative incidence of oncologic events was compared between the two groups, after stratifying patients by the time interval between mastectomy and the second-stage operation (≤ 12 months vs.12 months).Of 267 cases that met the selection criteria, 203 underwent the second-stage operation within 12 months of mastectomy. AFG was performed for 112 cases and was not performed in 91 cases. The two groups showed similar baseline characteristics including tumor stage and adjuvant treatments. Compared with the control, AFG was associated with lower locoregional recurrence-free survival and disease-free survival, and this difference remained significant after adjusting for other variables including tumor stage. In the 64 cases undergoing the operation after 12 months following mastectomy, oncologic outcomes did not differ between the two groups.Our results suggest that AFG timing in relation to mastectomy may be associated with risks for breast cancer recurrence.

A significant number of hereditary breast or ovarian cancers are caused by germline variants, mostly BRCA1/BRCA2 genes. Because genetic predispositions vary by ethnicity, several studies have reported founder variants of BRCA1/BRCA2 genes. Such founder variants were reported primarily based on their relevant population frequencies. We reviewed the variant data relating to BRCA1 and BRCA2 genes from January, 2012 to March 2019 at Samsung Medical Center, Seoul, Korea. Among the cases with pathogenic variants (PVs) or likely pathogenic variants (LPVs), we defined recurrent variants as those found in more than five unrelated patients. Using single nucleotide polymorphisms, we analyzed patient haplotypes. There were 14 recurrent variants in the BRCA1 gene and seven variants in the BRCA2 gene. Of note, three variants in each gene were primarily detected in Korean populations. Among them, the c.5339T > C BRCA1 variant had a long block sized 74.5 kb. In BRCA2, the c.1399A > T variant had a long block sized 35.5 kb. We suggest that BRCA1 c.5339T > C and BRCA2 c.1399A > T are founder variants of the Korean population. These two recurrent variants were ethnicity-prevalent, primarily found in Korean populations, and the sizes of the linkage disequilibrium blocks are longer than others.

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.

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.

Background: Most of breast cancer patients survive for a long-term period. The existing assessment of survivors’ prognosis has had some limitations in breast cancer because it is based on an evaluation at the time of diagnosis. Conditional survival reflects change over time after diagnosis and treatment of cancer. Conditional disease-free survival (CDFS) and conditional overall survival (COS) can provide more accurate prognosis to breast cancer patients. In this study, we aimed to determine 5-years CDFS and COS according to disease-free period after diagnosis and treatment of breast cancer in Korea. Method: We retrospectively reviewed clinical data of 5664 patients aged 16 to 86 who underwent curative surgery for breast cancer between January 2000 and December 2008 at Samsung Medical Center, a single tertiary hospital in Korea. The CDFS and COS rates were based on cumulative DFS and OS estimates up to 15 years using the Kaplan-Meier method. Results: At baseline, each 5-years DFS and OS were 88.0% and 93.8%. For patients who kept disease free status from 1 to 9 years after surgery, the 5-years CDFS rates were calculated as 88.7%, 90.7%, 91.6%, 91.1%, 91.5%, 91.0%, 89.5%, 86.1% and 86.1%, respectively. The 5-year COS rates of the patients who had survived from 1 to 9 years after surgical treatment were calculated as 92.6%, 92.1%, 91.2%, 91.0%, 89.4%, 85.6%, 80.7%, 75.3%, and 73.0%, respectively. Conclusion: Our study showed that 5-years CDFS and COS for most patients who have breast cancer in Korea seemed to be good prognosis for a long time. However, cancer recurrence tended to occur after a long period postoperatively. Further study is required to identify risk factors associated with recurrence after several years in Korean breast cancer patients. Citation Format: Jee Hyun Ahn, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jonghan Yu. The 5-years conditional disease free survival and overal survival for breast cancer patients in Korea [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-25.

Objective Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. Methods The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at Results All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P Conclusions BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.

Many breast cancer patients receive sentinel lymph node biopsy after neoadjuvant chemotherapy (NAC). We evaluated the axillary pathologic complete response (pCR) in relation to achievement of breast pCR. We evaluated 1044 patients who were diagnosed with invasive breast cancer and were treated with NAC followed by curative surgery at the Samsung Medical Center between January 2008 and December 2016. The pathologic node-positive rates in breast pCR patients were compared for different breast cancer subtypes and clinical nodal stages. Axillary pCR was achieved in 51.9% of the patients after NAC. In this case, the axillary pCR was associated with a biologic subtype (P

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (

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 (PVs/LPVs) were reviewed.ResultsA younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer (TNBC) and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All 7 cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected.ConclusionWe 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.

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.

The GenesWell™ BCT (BCT score) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and HER2 negative (HER2-) early breast cancer (BC). The ability of the assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date. Biopsy specimens of HR+/HER2- BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified breast cancer test (BCT) score was developed and classified into high-and low-response groups. A total of 88 patients were available for the BCT score among 108 eligible patients. The median follow-up duration was 35.9 (7.8-128.5) months. Among these, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or T2. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%) patients. Among 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high-response group, and 9 (18.0%) were in the low-response group. Among 38 patients with stable disease or progressive disease, 22 (57.9%) patients were in the high-response group, and 16 (42.1%) were in the low-response group (p = 0.025). Ki-67 before NACT was a significant factor for predicting tumor response (p = 0.006; 3.81 [1.50-10.16]). The BCT score showed a significant response to NACT (p = 0.016; 4.18 [1.34–14.28]). A significant difference was found in distant metastasis-free survival between the high and low response groups (p = 0.004). We demonstrated that the BCT score predicts NACT responsiveness of HR+/HER2- BC with LN metastasis and might help determine whether to undergo NACT or not. Further studies are warranted to validate these findings.

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)

531 Background: While the relationship between mammographic breast density (MD) decline and anti-hormone therapy efficacy has been reported in estrogen-receptor (ER)-positive breast cancer, it is still unclear in premenopausal women and in the case of adding ovarian function suppression (OFS) to anti-hormone therapy. We aimed to investigate the MD reduction (MDR) rate and impact of MDR on prognosis stratified by treatment from the updated result of the ASTRRA trial. Methods: ASTRRA trial, a randomized phase 3 study, showed that adding ovarian function suppression (OFS) to tamoxifen (TAM) improved survival in premenopausal women with ER+ breast cancer after chemotherapy. We updated survival outcomes with a median follow-up of 108 months. We assessed mammography taken before treatment and the follow-up mammography taken annually for up to five years after initiation of treatment. MD was classified into four categories based on the Breast Imaging Reporting and Data System. MDR positivity was defined as a downgrade in MD among follow-up mammography up to two years after randomization, with the pretreatment MD grade as a reference. Results: Among the 1,293 patients from ASTRRA trial, we successfully evaluated MDR in 947 patients, of which 796 (83.4%) belong to high MD (grade C or D). The patient characteristics were similar between the entire ASTRRA trial and the subgroup with available MDR. There was no difference in MDR-positive rate between two treatment groups (106 of 477 [22.2%] in TAM-only group vs. 87 of 470 [18.5%] in TAM + OFS group, P =.156). MDR-positivity was significantly associated with better disease-free survival (DFS) in TAM + OFS group (estimated 8-year DFS: 92.9% in MDR-positive vs. 82.2% in MDR-negative, P =.013), but did not in TAM-only group (estimated 8-year DFS: 80.3% in MDR-positive vs. 80.2% in MDR-negative, P =.927; Pinteraction =.025). Simialr trends were observed in terms of recurrence-free survival, distant metastasis-free survival (DMFS), locoregional-free survival, and overall survival. In addition, MDR-positivity was an independent factor for favorable DFS (adjusted hazard ratio [HR], 0.37; 95% CI, 0.16 to 0.86; P =.021) and DMFS (adjusted HR, 0.35; 95% CI, 0.13 to 0.98; P =.045) in TAM + OFS group. Conclusions: Although the proportion of patients with MDR-positive was comparable between the two treatment groups, MDR-positive was independently associated with favorable outcomes only in TAM + OFS group. Future work is warranted to verify the mechanism by which the association between MDR and clinical benefit differs according to the treatment group. Clinical trial information: NCT00912548.

506 Background: Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial, at 63 months median follow-up, showed that the addition of 2 years of ovarian function suppression (OFS) to Tamoxifen (TAM) significantly improved disease-free survival (DFS) compared with TAM alone in patients with hormone receptor–positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. We report updated long-term outcomes from ASTRRA trial with 106.4 months median follow-up. Methods: This study is a post-trial follow-up of the ASTRRA trial, which randomly assigned 1,298 patients with breast cancer in a 1:1 ratio to receive TAM only (n = 647) or TAM + OFS (n = 635). The primary endpoint was DFS and secondary endpoint was overall survival (OS). We used Kaplan-Meier estimates for time to event endpoints and hazard ratios (HR) with 95% confidence interval (CI) from Cox-regression model. Results: At 106.4 months of median follow-up, there continues to be a statistically significant reduction in DFS event rate in favor of the TAM+OFS group. The estimated 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (HR 0.67; 95% CI, 0.51 to 0.87). There were no significant differences in OS between two groups. The estimated 8-year OS rate was 96.5% in the TAM + OFS group and 95.3% in the TAM-only group (HR, 0.78; 95% CI, 0.49 to 1.25). The results of DFS and OS between the two groups defined from the time of random assignment to the time of events were also similar. Conclusions: These data demonstrate consistent survival advantages of adding OFS 2 years to TAM treatment over time, with the long-term follow-up reported to date. This study finding suggest that adding OFS to TAM should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy. Longer follow-up is needed to fully evaluate the OS benefit.

576 Background: To obtain a clear resection margin during breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NCT), accurate targeting of the location and assessment extent of the tumor are essential. However, conventional targeting methods such as USG/MMG guided hook wire insertion have disadvantages in that they could only localize the tumor, not reflecting its extent. To assess this problem, we developed an MRI-based 3D printed breast surgical guide (3DP-BSG) and conducted a multicenter randomized clinical study to prove its clinical effectiveness. Methods: In this multicenter, randomized (1:1), controlled trial (KCT0004469), we assigned 566 patients who underwent NCT and planned to undergo BCS, to use customized 3DP-BSG for lumpectomy, or not to use 3DP-BSG for lumpectomy. We assumed that 3DP-BSG group achieve non-inferior outcomes compared with control group with conventional targeting method. The primary endpoint was the margin positivity of the first resected margin. Under the assumption that the proportion of margin positivity would be 23% in both groups, a total of 438 patients were calculated to have 80% power to establish non-inferiority with a margin of 10% at a one-sided significance level of 0.05. Efficacy was assessed in the intention-to-treat (ITT) population. Results: Between 2019 and 2021, 282 (49.8%) patients were assigned to 3DP-BSG group, and 284 (50.2%) patients were assigned to control group with conventional targeting method. The median age was 51 years. In the ITT analysis, first resected margin was positivity in 5 (2.1%) of 235 patients in 3DP-BSG group and 7 (2.9%) of 244 patients in control group (difference -1.15 [95% CI -3.58 to -1.28], pnon-inferiority

10586 Background: Enabling equitable access to healthcare services among women remains a challenge in Asia. Differences in the presentation and treatment stage contribute to disparities in cancer outcomes. Genetic testing provides accurate risk assessment to help guide personalised preventative and treatment options. However, there is a critical need for research to further our understanding of barriers in leveraging optimal benefits of genetic testing and counselling (GT&C) to address cancer among women. Methods: A team of multinational experts was assembled to form the Asian Consensus and Recommendations on Genetic Testing and Counselling (ACROSS) Consortium to assess the challenges in adoption of GT&C for patients with breast and ovarian cancer in Asia. Critical publications were identified, and a pre-meeting questionnaire was developed. The questionnaire was refined to align with the objectives over iterations, and final approval was obtained from the steering committee. Survey responses were gathered from oncologists from ten countries across Asia. The expert committee discussed the survey results to highlight (1) current knowledge, attitude, and practices; (2) unmet needs and gaps; and (3) recommendations for addressing critical obstacles. Results: Adoption of GT&C for cancer is low in Asia. Lack of time, resources, and access to genetic counsellors are major difficulties faced. In most cases, the practising oncologists provide pre-test genetic counselling and communicate test results. For breast cancer (BC), most experts preferred germline testing only, with few opting for somatic testing if germline testing was negative. The agreement was lower among the ovarian cancer (OC) experts, with advocates for either germline or somatic testing or both. There was a lack of consensus on clinical criteria for selecting suitable candidates for genetic testing and the use of multiple gene panel germline testing. The need for government-aided subsidies and training programmes was highlighted. Conclusions: Recommendations from the expert panel included (1) development of guidelines and criteria to identify candidates suitable for GT&C; (2) training healthcare professionals with required competencies; (3) improving accessibility and affordability; (4) increased patient education and awareness; and (5) adoption of GT&C into the national healthcare system. The consortium agreed that a multifaceted plan of action combining the expertise of clinicians, scientists, and policymakers is required to facilitate uptake of GT&C in Asia. [Table: see text]

Purpose The purpose of this study was to investigate risk factors for post-metastasis overall survival (PMOS), and to analyze the effect of early detection of distant metastases before symptoms occur on survival in breast cancer patients under intensive surveillance.Methods A total of 7,840 patients underwent surgery for breast cancer from January 2010 to December 2014 at Samsung Medical Center; of these, we retrospectively studied 316 metastatic breast cancer patients. The patients were divided into two groups based on method of metastases detection, routine surveillance without symptoms (asymptomatic group) or follow-up for new-onset symptoms (symptomatic group).Results Multivariate analysis of PMOS showed that the patients with multiple metastases had a 1.872 fold risk of PMOS (p = 0.011) compared to the patients with bone metastasis only. The hazard ratio for the symptomatic group was higher than that for the asymptomatic group (p < 0.001). When patients were stratified by tumor subtype, patients who were HR-positive and asymptomatic on diagnosis of distant metastasis had a better prognosis than those who were HR-positive and symptomatic on diagnosis. However, patients who were HER2-positive showed no significant survival difference between two groups.Conclusion Breast cancer patients who were diagnosed with distant metastasis after symptoms occurred had a poorer prognosis than patients who were diagnosed before symptoms had developed. It is important to follow up patients regularly for symptoms related to distant metastases. Our findings validate the need for intensive surveillance, suggesting reconsideration of the guidelines for metastases screening in breast cancer patients.

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 p = 0.775) or radiotherapy (p = 0.825) were not risk factors for postoperative complications. Conclusions IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR. Trial registration Patients were selected and registered retrospectively, and medical records were evaluated.

Background: The predictive value of adjuvant chemotherapy for early-stage hormone receptor-positive breast cancer has been only validated by a 21-gene expression assay. We hypothesized that deep-learning prediction from HE images, called Lunit-SCOPE, is a potential prognostic and predictive biomarker of adjuvant chemotherapy.Methods: We retrospectively collected HE slides from 1153 de-identified breast cancer patients at the Samsung Medical Center (SMC) in order to develop a deep-learning algorithm called Lunit-SCOPE. The histological parameters from 255 patients, deciphered by Lunit-SCOPE, were trained to predict the recurrence score (RS) using the 21-gene assay from Oncotype DX. We validated the model’s performance using the recurrence survival of 898 patients and The Cancer Genome Atlas (TCGA) cohort, and examined related biological functions through RNA sequence data.Results: The histologic parameter-based RS prediction model predicted the oncotype DX score (R2=0.96) and the recurrence survival analysis on the validation (pppConclusion: An integrative analysis using Lunit-SCOPE predicts a high risk of recurrence and those who would benefit from adjuvant chemotherapy for early-stage hormone-positive breast cancer.

Purpose Restricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND. Methods We designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period). Results A total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (-30.04 ± 27.76 vs. -42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (-3.92 ± 9.80 vs. -10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group. Conclusion We suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND. Trial registration ClinicalTrials.gov Identifier: NCT02967146.

BACKGROUND In hereditary breast and ovarian cancer (HBOC), family communication of genetic test results is essential for cascade genetic screening, that is, identifying and testing blood relatives of known mutation carriers to determine whether they also carry the pathogenic variant, and to propose preventive and clinical management options. However, up to 50% of blood relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively within family networks. Technology can facilitate communication and genetic education within HBOC families. OBJECTIVE The aims of this study are to develop the K-CASCADE (Korean–Cancer Predisposition Cascade Genetic Testing) cohort in Korea by expanding an infrastructure developed by the CASCADE (Cancer Predisposition Cascade Genetic Testing) Consortium in Switzerland; develop a digital health intervention to support the communication of cancer predisposition for Swiss and Korean HBOC families, based on linguistic and cultural adaptation of the Family Gene Toolkit; evaluate its efficacy on primary (family communication of genetic results and cascade testing) and secondary (psychological distress, genetic literacy, active coping, and decision making) outcomes; and explore its translatability using the reach, effectiveness, adoption, implementation, and maintenance framework. METHODS The digital health intervention will be available in French, German, Italian, Korean, and English and can be accessed via the web, mobile phone, or tablet (ie, device-agnostic). K-CASCADE cohort of Korean HBOC mutation carriers and relatives will be based on the CASCADE infrastructure. Narrative data collected through individual interviews or mini focus groups from 20 to 24 HBOC family members per linguistic region and 6-10 health care providers involved in genetic services will identify the local cultures and context, and inform the content of the tailored messages. The efficacy of the digital health intervention against a comparison website will be assessed in a randomized trial with 104 HBOC mutation carriers (52 in each study arm). The translatability of the digital health intervention will be assessed using survey data collected from HBOC families and health care providers. RESULTS Funding was received in October 2019. It is projected that data collection will be completed by January 2023 and results will be published in fall 2023. CONCLUSIONS This study addresses the continuum of translational research, from developing an international research infrastructure and adapting an existing digital health intervention to testing its efficacy in a randomized controlled trial and exploring its translatability using an established framework. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Culturally sensitive web-based interventions that enhance family communication and understanding of genetic cancer risk are timely. This collaboration creates a research infrastructure between Switzerland and Korea that can be scaled up to cover other hereditary cancer syndromes. CLINICALTRIAL ClinicalTrials.gov NCT04214210; https://clinicaltrials.gov/ct2/show/NCT04214210 and CRiS KCT0005643; https://cris.nih.go.kr/cris/ INTERNATIONAL REGISTERED REPORT PRR1-10.2196/26264

Background: Immediate breast reconstruction with tissue expander in 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 1,081 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 1,022 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 < 0.001). Chemotherapy (p = 0.775) or radiotherapy (p = 0.825) were not risk factors for postoperative complications.Conclusions: IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR.

Purpose Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. Methods Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. Results Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. Conclusion As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Background: Immediate breast reconstruction with tissue expander in 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.Method: We conducted a retrospective study of 1,081 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). The complication group had 59 patients (5.5%) and the no complication group had 1,022 patients (94.5%). Results: In univariate analysis, lymphovascular invasion (LVI), pathologic N stage, pathologic prognostic stage, axillary lymph node dissection (ALND), adjuvant radiotherapy, and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, higher pathologic N stage was significantly associated with postoperative complications. Chemotherapy or radiotherapy were not risk factors for postoperative complications.Conclusions: IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid preoperative counseling to patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy.

To examine the association between obesity measured by body mass index (BMI) and waist circumference (WC) according to menopausal status in Korean women.We identified 6,467,388 women, using the Korean National Health Insurance System Cohort. Cox-proportional hazard models were used to generate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for breast cancer risk in relation to BMI and WC.In postmenopausal women, the risk of breast cancer increased with BMI. Compared to women with a BMI of 18.5-23 kg/m two, the risk of invasive breast cancer was lower in patients with BMI 18.5 (aHR 0.82, 95% CI 0.75-0.89), while it increased linearly in those with BMI 23-25 (1.11, 1.08-1.14), BMI 25-30 (1.28, 1.25-1.32), and BMI ≥ 30 (1.54,1.47-1.62). In contrast, the risk of breast cancer decreased with BMI in premenopausal women. Compared to women with a BMI of 18.5-23, the risk of IBC was similar in those with a BMI 18.5 (1.02, 0.94-1.11) and BMI 23-25 (1.01, 0.97-1.05), but was significantly lower in those with a BMI 25-30 (0.95, 0.91-0.98) and BMI ≥ 30 (0.90, 0.82-0.98). A relative increase with BMI was less profound for carcinoma in situ in postmenopausal women, and a relative decrease was more profound in premenopausal women. An analysis using WC showed almost identical results.There was a positive relationship between obesity and breast cancer in postmenopausal women, and an inverse association in premenopausal women.

Introduction Tumor metastasis is a major clinical challenge accounting for the vast majority of cancer related deaths.In previous studies, prediction of distant metastasis was based on subtypes,clinical status and sometimes gene expression were used however clinical application was difficult. In this study, we develop the easy to use prediction tool for distant metastasis using clinical characteristics and gene profiles which came from CancerSCANTM, Next Generation Sequencing based targeted-sequencing platform designed at Samsung Medical Center(SMC). Methods We performed a retrospective chart review of 326 breast cancer patients who underwent surgery and CancerSCAN TM between Jan 2001 and Dec 2014 at SMC. Median follow up period was 83 months (Range 1˜190). Cancer scanTM cover 381 genes but 27 genes and 34 occasions (loss of function, mutation or copy number variation) were selected for analysis through gradient boosting and Wilcoxon Signed rank test. Azure Machine Learning is a cloud service that enables the execution of machine learning processes.This was accomplished using the steps of (1) edit the data, (2) split the data, (3) train the model, (4) score the model, and (5) evaluate the model. We split the modeling data into training and testing sets using a randomized 50–50 split. Two-class Decision Forest method was used. After deploying the Azure ML predictive model as a web service, we used a Representational State Transfer application programming interface to send data and obtained predictions in real-time. Results No distant metastasis group and distant metastasis group consisted of 267 and 59 patients, respectively. HR-/HER2+ and 50 years old and over patients were higher in metastasis group (p-value = 0.003 and p-value = 0.000). Nuclear grade 3 and N2,3 were higher in metastasis group (p-value = 0.010 and p-value = 0.000, p-value = 0.001 respectively). Stage III was also higher in metastasis group (p-value = 0.000). Among 59 patients with distantmetastasis, multiple sites metastasis was 21 cases (35.6%) and then lung metastasis was 19 cases (32.2%). In the 21 cases of multiple sites metastasis, triple sites was 6 cases (28.6%) and double sites was 15 cases (71.4%). PIK3CA mutation was the most frequent gene variation in all patients (34.5% of no metastasis group and 27.1% of metastasis group) but there was no difference between two groups(p-value = 0.278). BRCA 1 loss of function and BRCA2 loss of function were more frequent in metastasis group than no metastasis group(p-value = 0.033 and p-value = 0.024, respectively) but total counts was too small. We assessed the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for predictive value. The AUC of ROC curve was 1.000 and also accuracy, precision, recall were 1.000. In addition, we conducted internal validation using 83 patients during 2015. When we applied a 0.5 threshold value with our predictive model, true negative was 81 and true positive was 2 among 83 patients. Finally, the accuracy of validation was 1.000. Conclusion Our predicted model could represent a useful and easy-to-access tool for the selection of patients with distant metastasis. After additional evaluation with large data and external validation, worldwide use of our model could be expected. Citation Format: Kim I, Choi HJ, Ryu JM, Lee SK, Yu JH, Kim SW, Nam SJ, Seo SW, Lee JE. A predictive model for distant metastasis in breast cancer patients using machine learning [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-52.

Background: There are many factors that might contribute to the delay of surgery in patients with breast cancer. Previous studies investigate the influence of delay of surgery, but they reported inconsistent results. The purpose of this study was to evaluate the impact of time of surgery on prognosis of breast cancer. Methods: We performed a retrospective review of the patients with breast cancer, who received surgery between 1992 and 2009, by using data from Korea Breast Cancer Society Registry. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the impact of time to surgery in breast cancer and subgroup analyses were performed for each disease stage and molecular subtype. Result: A total 14727 patients were included for analysis. Delay of surgery more than 31 days was associated with worse survival for breast cancer [hazard ratio (HR) = 2.16; 95% confidence interval (CI), 1.936-2.408, p Conclusion: Surgical delay of more than 31 days were independent risk factors for worse outcome of breast cancer in each molecular subtype and breast cancer group except stage 0 and I. Although preoperative evaluation is required, surgical delay should be shortened to enhance survival of breast cancer, especially in patients with tumor size more than 2cm or presence of lymph node metastasis. Citation Format: Kim J-M, Choi HJ, Kim I, Ryu JM, Yu J, Lee JE, Kim SW, Nam SJ, Lee SK. The impact of time interval between diagnosis and surgery in each type and stage of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-29.