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Several studies have revealed a possible association between antibiotic use and breast cancer in the Western population of women. However, its association with the Asian population remains unclear. Data utilized in this nationwide population-based retrospective cohort study were obtained from the Korean National Health Insurance Service database. The study population consisted of 4,097,812 women who were followed up from January 1, 2007, to December 31, 2019. Cox proportional hazards regression was utilized to calculate adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the risk of breast cancer according to cumulative days of antibiotic use and the number of antibiotic classes used. It was discovered that women who used antibiotics for more than 365 days had a higher risk of breast cancer (aHR, 1.15; 95% CI, 1.09-1.21) in comparison with those who did not use antibiotics. In addition, an association was found among women who used five or more classes of antibiotics, showing a higher risk of breast cancer (aHR, 1.11; 95% CI, 1.05-1.17) compared with nonusers. Furthermore, compared with antibiotic nonusers, only users of cephalosporins (aHR, 1.09; 95% CI, 1.02-1.17) and lincosamides (aHR, 1.70; 95% CI, 1.20-2.42) had a higher risk of breast cancer. These findings support epidemiologic evidence that long-term use of antibiotics may be associated with a higher risk of breast cancer. This underscores the need for further studies to address the potential for residual confounding, confirm causation, and elucidate the underlying mechanisms. Prevention Relevance: This study found a probable duration-dependent association between antibiotic prescriptions and breast cancer risk. The findings indicate that long-term antibiotic use could be associated with an increased risk of breast cancer and highlight the need for further research to confirm causality and mechanisms., (©2024 American Association for Cancer Research.)

Background: Pathology reports provide important information for accurate diagnosis of cancer and optimal treatment decision making. In particular, breast cancer has known to be the most common cancer in women worldwide., Objective: For the data extraction of breast cancer pathology reports in a single institute, we assessed the accuracy of methods between regular expression and natural language processing (NLP)., Methods: A total of 1,215 breast cancer pathology reports were annotated for NLP model development. As NLP models, we considered three BERT models with specific vocabularies including BERT-basic, BioBERT, and ClinicalBERT. K-fold cross-validation was used to verify the performance of the BERT model. The results between the regular expression and the BERT model were compared using the named entity recognition (NER) techniques., Results: Among three BERT models, BioBERT was the most accurate parsing model (average performance =  0.99901) for breast cancer pathology when set to k = 5. BioBERT also had the lowest error rate for all items in the breast cancer pathology report compared to other BERT models (accuracy for all variables ≥ 0.9). Therefore, we finally selected BioBERT as the NLP model. When comparing the results of BioBERT and regular expressions using NER, we identified that BioBERT was more accurate than regular expression method, especially for some items such as intraductal component (BioBERT: 1.0, RegEx: 0.1644), lymph node (BioBERT: 0.9886, RegEx: 0.4792), and lymphovascular invasion (BioBERT: 0.9918, RegEx: 0.3759)., Conclusions: Our results showed that the NLP model, BioBERT, had higher accuracy than regular expression, suggesting the importance of BioBERT in the processing of breast cancer pathology reports., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To compare mammography, breast ultrasound (US), high-resolution diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced breast MRI (DCE-MRI), and their combinations for detecting clinically occult early breast cancers (EBCs), including ductal carcinoma in situ (DCIS)., Methods: Three hundred and three consecutive women with screening imaging-detected early breast cancers (60 pure DCIS, 36 DCIS with microinvasion, and 207 invasive carcinoma less than 20 mm) who underwent breast MRI at 3 T including DW-MRI (b-values of 0, 800 and 1200 s/mm 2 ; in-plane resolution, 1.1 × 1.1 mm 2 or 1.3 × 1.3 mm 2 ; section thickness, 3 mm) were retrospectively reviewed. Three radiologists independently reviewed each examination. Statistical analysis included Chi-square test, McNemar test for comparison of cancer detection rates, and Fleiss' Kappa for interreader agreement. Mixed-effect logistic regression analysis was employed to evaluate factors associated with cancer detection on DW-MRI., Results: The overall cancer detection rates were 54.8% on mammography, 71.0% on breast US, 81.5% on DW-MRI, and 87.1% on DCE-MRI. On McNemar test, DW-MRI detected more cancers than mammography (adjusted p < 0.001), and its combination with mammography showed a similar cancer detection rate to DCE-MRI combined with mammography (adjusted p = 0.808). On multivariable analysis, histologic type, lesion size, ADC and CNR on DW-MRI were independent factors for cancer detection on DW-MRI. The interreader agreement for cancer detection was moderate to substantial (Fleiss' kappa: 0.52-0.65) across each modality., Conclusion: High-resolution DW-MRI plus mammography showed comparable cancer detection rate to DCE-MRI plus mammography for detecting clinically occult EBCs including DCIS., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethical approval: This retrospective study received approval from the Institutional Review Board of our institution and was performed in accordance with the relevant guidelines and regulations. The requirement for informed patient consent was waived., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy. This retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT. 203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2-96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences. The application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We investigated the safety and performance of the Da Vinci SP single-port robot (SP robot) in nipple-sparing mastectomy (NSM) with immediate reconstruction. Medical records of 60 women aged ≥ 19 years who had undergone SP robot-assisted unilateral or bilateral NSM with immediate reconstruction between October 2020 and August 2021 were retrospectively analyzed. Stage I (31, 47.1%) was the most common pathological tumor-node-metastasis stage, followed by stages II (22, 33.3%), 0 (7, 10.6%), and III (4, 6.0%). The median total duration of NSM performed by a breast surgeon and reconstruction performed by a plastic surgeon was 154.0 min (interquartile range [IQR], 130.5-206.0 min) and 133.0 min (IQR, 80.0-255.0 min), respectively. The median length of hospitalization was 5.5 days (IQR, 3.0-9.0 days). Conversion to robotic multiport or open surgery was not required in any case. The median duration to drain removal was 5.0 days (IQR, 4.0-6.0 days). Recurrence of cancer within 6 months was not observed in any patient. SP robot-assisted NSM with immediate reconstruction was performed successfully in all patients without conversion to open surgery or the incidence of significant perioperative complications, indicating its precision and ability to minimize the size of the surgical incision., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was waived because the study was based on retrospective clinical data., (© 2024. The Author(s).)

Extracellular vesicles (EVs) from brain-seeking breast cancer cells (Br-EVs) breach the blood-brain barrier (BBB) via transcytosis and promote brain metastasis. Here, we defined the mechanisms by which Br-EVs modulate brain endothelial cell (BEC) dynamics to facilitate their BBB transcytosis. BEC treated with Br-EVs show significant downregulation of Rab11fip2, known to promote vesicle recycling to the plasma membrane and significant upregulation of Rab11fip3 and Rab11fip5, which support structural stability of the endosomal compartment and facilitate vesicle recycling and transcytosis, respectively. Using machine learning and quantitative global proteomic, we identified novel Br-EV-induced changes in BECs morphology, motility, and proteome that correlate with decreased BEC cytoplasm and cytoskeletal organization and dynamics. These results define early steps leading to breast-to-brain metastasis and identify molecules that could serve as targets for therapeutic strategies for brain metastasis., (© 2025 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Purpose: During breast cancer surgery, the use of dyes such as indigo carmine, methylene blue, or indocyanine green (ICG) for targeting axillary lymph nodes (ALNs) under ultrasound guidance can result in rapid diffusion, complicated tissue differentiation, and disruption of staining. LuminoMark™, a novel ICG-hyaluronic acid mixture, can provide real-time visualization and minimize dye spread, thereby ensuring a clear surgical field. The aim of our study was to evaluate the efficacy of LuminoMark™ for targeting ALNs in patients with breast cancer., Methods: A total of 13 patients with breast cancer (mean age 56.5 years; 92.3% female) and suspicious ALNs underwent targeted axillary surgery (TAS) with activated charcoal and LuminoMark™ injected into the LNs in the surgical field. The clinicopathological variables of the patients and diagnostic performance were assessed. The LNs injected with LuminoMark™ were examined for consistency with sentinel LNs (SLNs) and non-SLNs, as well as with charcoal-tattooed LNs., Results: The identification of SLNs took approximately 15.6 min from the start of skin incision, and it required 25.6 and 17.7 min, for charcoal-tattooed and LuminoMark TM -illuminated LNs, respectively. The identification rate was 92.3% with charcoal and 100% with LuminoMark™. The concordance rate between LuminoMark™ illumination and SLNs was higher than that between charcoal tattooing and SLNs. The concordance rate between the two methods was 76.9% (n = 10). Three months after surgery, the charcoal tattoo remained visible on the skin; however, LuminoMark™ was not visible., Conclusion: Although both methods demonstrated high detection rates, the rate was higher using LuminoMark™. As LuminoMark™ was administered directly into LNs, this improved the accuracy of identifying LNs., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Kyungpook National University Chilgok Hospital (KNUCH 2023-12-029). The specific inclusion and exclusion criteria were defined according to an approved institutional review board protocol. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

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 (< 35 vs. 45, HR 7.85, 95% CI 4.63-13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37-2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 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., (© 2024. The Author(s).)

Background Breast nonmass lesions (NMLs) are observed at screening and diagnostic US. However, knowledge is limited on imaging features of NMLs at screening US. Purpose To identify features of NMLs at screening US that are suspicious for malignancy based on mammographic findings. Materials and Methods This retrospective, multicenter study included asymptomatic women who underwent screening US between January 2012 and December 2019. Eligible women had NMLs at US, concurrent screening mammography, and record of a final diagnosis. Logistic regression analyses were used to identify factors associated with malignancy. The diagnostic performance of each sonographic feature according to mammographic findings was calculated. A reader study was performed to assess interreader agreement for sonographic features. Results Among 993 NMLs in 993 patients (mean age, 50 years ± 9 [SD]), 914 (92.0%) were benign and 79 (8.0%) were malignant. Mean size was larger for malignant NMLs than for benign NMLs (2.6 cm ± 1.1 vs 1.9 cm ± 0.8; P < .001). In multivariable analysis, associated calcifications (odds ratio [OR], 21.6 [95% CI: 8.0, 58.2]; P < .001), posterior shadowing (OR, 6.9 [95% CI: 2.6, 18.4]; P < .001), segmental distribution (OR, 6.2 [95% CI: 2.7, 14.4]; P < .001), mixed echogenicity (OR, 5.0 [95% CI: 1.8, 14.0]; P < .001), and size (OR, 1.5 [95% CI: 1.1, 2.1]; P = .01) at US were associated with malignancy. Associated calcifications, posterior shadowing, segmental distribution, and mixed echogenicity showed positive predictive values (PPVs) of 44%, 22%, 22.9%, and 16.6%, respectively. Having a negative mammogram was associated with a lower malignancy rate (2.8% vs 28.8%) and lower PPVs for sonographic features (0.7%-10.4% vs 24%-55%) than having a positive mammogram. Interreader agreement for sonographic features was good to excellent (Fleiss κ 95% CI lower bound range, 0.63-0.81). Conclusion Calcifications, posterior shadowing, segmental distribution, and mixed echogenicity associated with NMLs can be considered suspicious features for malignancy at screening US. As malignancy rates and PPVs differ according to mammographic abnormalities, combined assessment is mandatory. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

The clinical impact of 16α- 18 F-fluoro-17β-estradiol ( 18 F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18 F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18 F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor-positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18 F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18 F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18 F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18 F-FES PET/CT. In 139 (40%) patients, 18 F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18 F-FES-negative (44% [36/81]) than 18 F-FES-positive (30% [51/172]) or mixed 18 F-FES-positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18 F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Ipsilateral breast tumor recurrence (IBTR) remains a concern despite standard treatments. Advances in early detection have shifted surgical paradigms towards less invasive approaches. While repeat sentinel lymph node biopsy (rSLNB) emerges as a viable option according to the 2023 National Comprehensive Cancer Network (NCCN) guidelines, its efficacy remains uncertain. This study aimed to assess lymphatic drainage patterns in IBTR and evaluate the feasibility of rSLNB, along with analyzing oncologic outcomes., Methods: A retrospective analysis involving 78 patients with IBTR who had prior breast-conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) and adjuvant whole breast irradiation (WBI) at Samsung Medical Center was conducted. Data on patient characteristics, lymphatic mapping techniques, and oncologic outcomes were collected and analyzed., Results: Among 78 patients with IBTR, 82.1 % underwent successful rSLNB, predominantly detecting lymphatic drainage to the ipsilateral axilla (80.8 %). The initial tumor location correlated significantly with failed lymphatic mapping (p = 0.019). A third event occurred in 28.8 % of invasive IBTR cases, notably associated with postmenopausal status, higher T stages, and HR(-)/HER2(-) subtype (p < 0.001). The risk of a third event increased by over 50 % within a 2-year interval post-IBTR., Conclusion: rSLNB in patients with IBTR, particularly for tumors initially located outside the upper-outer quadrant, demonstrated technical feasibility. The combined use of blue dye with lymphoscintigraphy may enhance rSLNB success rates. Active surveillance, especially for triple negative IBTR cases, may be important due to their aggressive nature and rapid progression potential within a short interval post-IBTR., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In this study, the authors compared conventional and robot-assisted mastectomy and breast reconstruction. To the authors' knowledge, this study is the first to report the results of robot-assisted mastectomy and breast reconstruction and provide a comparison of patient-reported outcomes., Method: This retrospective study included 473 breasts of 423 patients who underwent conventional mastectomy and breast reconstruction and 164 breasts of 153 patients who underwent robot-assisted mastectomy and breast reconstruction from July of 2019 to October of 2021. Demographic and oncologic data, reconstructive outcomes, and patient-reported outcomes (BREAST-Q) were evaluated. The results of implant-based and autologous breast reconstruction were evaluated separately., Results: Skin necrosis requiring surgical débridement occurred significantly more frequently in the conventional group (8.0%) than in the robot-assisted group (2.0%) in implant-based reconstruction ( P = 0.035). At 6 to 12 months, patients who underwent robot-assisted breast reconstruction showed a higher Sexual Well-being score for implant-based reconstruction and a higher Physical Well-being score for autologous breast reconstruction than conventional breast reconstruction according to the BREAST-Q questionnaire., Conclusions: Robot-assisted mastectomy and breast reconstruction was associated with less skin necrosis and better patient-reported outcomes (Sexual Well-being for implant-based reconstruction and Physical Well-being for autologous breast reconstruction) than the conventional option. Robotic surgery could be a good option for mastectomy and breast reconstruction., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Objectives: To evaluate the use of a commercial artificial intelligence (AI)-based mammography analysis software for improving the interpretations of breast ultrasound (US)-detected lesions., Methods: A retrospective analysis was performed on 1109 breasts that underwent both mammography and US-guided breast biopsy. The AI software processed mammograms and provided an AI score ranging from 0 to 100 for each breast, indicating the likelihood of malignancy. The performance of the AI score in differentiating mammograms with benign outcomes from those revealing cancers following US-guided breast biopsy was evaluated. In addition, prediction models for benign outcomes were constructed based on clinical and imaging characteristics with and without AI scores, using logistic regression analysis., Results: The AI software had an area under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI, 0.79-0.82) in differentiating between benign and cancer cases. The prediction models that did not include AI scores (non-AI model), only used AI scores (AI-only model), and included AI scores (integrated model) had AUROCs of 0.79 (95% CI, 0.75-0.83), 0.78 (95% CI, 0.74-0.82), and 0.85 (95% CI, 0.81-0.88) in the development cohort, and 0.75 (95% CI, 0.68-0.81), 0.82 (95% CI, 0.76-0.88), and 0.84 (95% CI, 0.79-0.90) in the validation cohort, respectively. The integrated model outperformed the non-AI model in the development and validation cohorts (p < 0.001 for both)., Conclusion: The commercial AI-based mammography analysis software could be a valuable adjunct to clinical decision-making for managing US-detected breast lesions., Clinical Relevance Statement: The commercial AI-based mammography analysis software could potentially reduce unnecessary biopsies and improve patient outcomes., Key Points: • Breast US has high rates of false-positive interpretations. • A commercial AI-based mammography analysis software could distinguish mammograms having benign outcomes from those revealing cancers after US-guided breast biopsy. • A commercial AI-based mammography analysis software may improve interpretations for breast US-detected lesions., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer., Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival., Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index., Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive., Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities., Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy., Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients., (© 2024. The Author(s).)

Purpose: The use of advanced energy devices for mastectomy and axillary lymph node dissection can reduce perioperative blood loss, seroma formation, and drainage duration/volume. Retraction using fiberoptic retractors can help visualize deep and narrow surgical fields. We aimed to compare the postoperative outcomes between single-incision breast-conserving surgery (SIBCS) and conventional breast-conserving surgery (CBCS) with axillary staging using advanced energy devices and conventional equipment, respectively., Materials and Methods: We retrospectively reviewed the medical records of 244 patients who underwent BCS with axillary surgery between March 2018 and September 2019 at Severance Hospital. The patients were grouped based on the device used to aid in axillary staging: CBCS group (n=117) used conventional electrocautery; and SIBCS group (n=127) used advanced energy devices and fiberoptic retractors. The two groups were compared for postoperative outcomes., Results: The mean patient age was 55.9 and 53.1 years in the CBCS and SIBCS groups, respectively. Incision size was significantly smaller in the SIBCS group than in the CBCS group (6.3±2.1 cm vs. 7.5±2.5 cm, p =0.044). There were no significant differences between the two groups in terms of operating time (126.0±40.0 min vs. 127.0±63.0 min, p =0.828), operative blood loss (11.0±31.0 mL vs. 7.0±18.0 mL, p =0.100), drainage duration (7.0±3.0 d vs. 8.0±4.0 d, p =0.288), and complications (1.70% vs. 2.36%, p =0.523)., Conclusion: Using advanced energy devices for SIBCS with axillary staging reduced incision size and provided better cosmetic outcomes compared to those using the conventional method. Advanced energy devices may offer better surgical outcomes in patients who undergo BCS with axillary staging., Competing Interests: Hyung Seok Park has received honoraria from AstraZeneca, Takeda, Ethicon, Medtronic, and Intuitive Surgical. The rest of co-authors have no conflict of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Objective: Dual-layer CT (DLCT) can create virtual monochromatic images (VMIs) at various monochromatic X-ray energies, particularly at low keV levels, with high contrast-to-noise ratio. The purpose of this study was to assess the clinical feasibility of contrast-enhanced chest DLCT with a low keV VMI for preoperative breast cancer staging, in comparison to breast MRI., Materials and Methods: A total of 152 patients with 155 index breast cancers were enrolled in the study. VMIs were generated from contrast-enhanced chest DLCT at 40 keV and maximum intensity projection (MIP) with three-dimensional (3D) reconstruction was performed for both bilateral breast areas. Two radiologists reviewed in consensus the 3D MIP images of the chest DLCT with VMI and breast MRI in separate sessions with a 3-month wash-out period. The detection rate and mean tumor size of the index cancer were compared between the chest DLCT with VMI and breast MRI. Additionally, the agreement of tumor size measurement between the two imaging modalities were evaluated., Results: Of all index cancers, 84.5% (131/155) were detected in the chest DLCT with VMI, while 88.4% (137/155) were detected in the breast MRI ( P = 0.210). The Bland-Altman agreement between the chest DLCT with VMI and breast MRI was a mean difference of -0.05 cm with 95% limits of agreement of -1.29 to 1.19 cm. The tumor size in the chest DLCT with VMI (2.3 ± 1.7 cm) was not significantly different from that in the breast MRI (2.4 ± 1.6 cm) ( P = 0.106)., Conclusion: The feasibility of chest DLCT with VMI was demonstrated for preoperative tumor staging in breast cancer patients, showing comparable cancer detectability and good agreement in tumor size measurement compared to breast MRI. This suggests that chest DLCT with VMI can serve as a potential alternative for patients who have contraindications to breast MRI., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes., Patients and Methods: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]., Results: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype)., Conclusions: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence., (© 2024. The Author(s).)

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11-6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18-2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92-3.68; IC = 1.53, 95%CrI = 1.35-1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions., (© 2024. The Author(s).)

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863)., Methods: We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise., Findings: Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months)., Interpretation: Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors., (© 2024. The Author(s).)

Purpose: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC)., Methods: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020., Results: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011)., Conclusion: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To determine the optimal angular range (AR) for digital breast tomosynthesis (DBT) systems that provides highest lesion visibility across various breast densities and thicknesses., Method: A modular DBT phantom, consisting of tissue-equivalent adipose and glandular modules, along with a module embedded with test objects (speckles, masses, fibers), was used to create combinations simulating different breast thicknesses, densities, and lesion locations. A prototype DBT system operated at four ARs (AR ±7.5° , AR ±12.5° , AR ±19° , and AR ±25° ) to acquire 11 projection images for each combination, with separate fixed doses for thin and thick combinations. Three blinded radiologists independently assessed lesion visibility in reconstructed images; assessments were averaged and compared using linear mixed models., Results: Speckle visibility was highest with AR ±7.5° or AR ±12.5° , decreasing with wider ARs in all density and thickness combinations. The difference between AR ±7.5° and AR ±12.5° was not statistically significant, except for the tube-side speckles in thin-fatty combinations (5.83 [AR ±7.5° ] vs. 5.39 [AR ±12.5° ], P = 0.019). Mass visibility was not affected by AR in thick combinations, while AR ±12.5° exhibited the highest mass visibility for both thin-fatty and thin-dense combinations (P = 0.032 and 0.007, respectively). Different ARs provided highest fiber visibility for different combinations; however, AR ±12.5° consistently provided highest or comparable visibility. AR ±12.5° showed highest overall lesion visibility for all density and thickness combinations., Conclusions: AR ±12.5° exhibited the highest overall lesion visibility across various phantom thicknesses and densities using a projection number of 11., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Evaluating the performance of a binary diagnostic test, including artificial intelligence classification algorithms, involves measuring sensitivity, specificity, positive predictive value, and negative predictive value. Particularly when comparing the performance of two diagnostic tests applied on the same set of patients, these metrics are crucial for identifying the more accurate test. However, comparing predictive values presents statistical challenges because their denominators depend on the test outcomes, unlike the comparison of sensitivities and specificities. This paper reviews existing methods for comparing predictive values and proposes using the permutation test. The permutation test is an intuitive, non-parametric method suitable for datasets with small sample sizes. We demonstrate each method using a dataset from MRI and combined modality of mammography and ultrasound in diagnosing breast cancer., Competing Interests: Seo Young Park, who holds the respective position of Statistical Consultant of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. The remaining authors have declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

Purpose: This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea., Materials and Methods: We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing., Results: From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively., Conclusion: The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Breast cancer patients experience significant distress relating to their diagnosis and treatment. Managing this distress is critical for improving the lifespan and quality of life of breast cancer survivors. This study aimed to assess the level of distress in breast cancer survivors and analyze the variables that significantly affect distress using machine learning techniques. A survey was conducted with 641 adult breast cancer patients using the National Comprehensive Cancer Network Distress Thermometer tool. Participants identified various factors that caused distress. Five machine learning models were used to predict the classification of patients into mild and severe distress groups. The survey results indicated that 57.7% of the participants experienced severe distress. The top-three best-performing models indicated that depression, dealing with a partner, housing, work/school, and fatigue are the primary indicators. Among the emotional problems, depression, fear, worry, loss of interest in regular activities, and nervousness were determined as significant predictive factors. Therefore, machine learning models can be effectively applied to determine various factors influencing distress in breast cancer patients who have completed primary treatment, thereby identifying breast cancer patients who are vulnerable to distress in clinical settings., (© 2024. The Author(s).)

Purpose: To compare the performance of mammography, high-resolution DW-MRI, DCE-MRI, and their combinations in detecting clinically occult breast cancer in women with dense breasts., Method: 544 breasts from 281 consecutive asymptomatic women with dense breasts were retrospectively identified. They underwent breast MRI for preoperative evaluation of breast cancers (n = 214) or as supplemental screening (n = 67) including DCE-MRI and DW-MRI (b values, 0 and 1000 sec/mm 2 ; in-plane resolution, 1.1 × 1.1 mm 2 and 1.3 × 1.3 mm 2 ; section thickness, 3 mm), in addition to mammography. Three readers independently reviewed each examination on a per-breast basis. Histopathology and at least two year of imaging follow-up served as the gold standard. The sensitivities and specificities of different imaging modalities were compared using McNemar test., Results: 230 of 544 breasts (42 %) had malignant lesions. The sensitivity of DW-MRI was higher than that of mammography (77.0 % vs 57.9 %; adjusted p < 0.001), but lower than that of DCE-MRI (84.8 %; adjusted p = 0.014). The specificity of DW-MRI was comparable to those of mammography (98.1 % vs 99.1 %; adjusted p > 0.999) and DCE-MRI (97.1 %; adjusted p > 0.999). DW-MRI plus mammography had a comparable sensitivity and specificity to those of DCE-MRI plus mammography (88.6 % vs 90.9 % and 97.1 % vs 96.2 %; adjusted p > 0.999 for both)., Conclusions: High-resolution DW-MRI had a sensitivity higher than mammography and lower than DCE-MRI. Nevertheless, DW-MRI plus mammography showed a comparable sensitivity and specificity to DCE-MRI plus mammography for detecting clinically occult cancers in women with dense breasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the improvement of mammography interpretation for novice and experienced radiologists assisted by two commercial AI software., Methods: We compared the performance of two AI software (AI-1 and AI-2) in two experienced and two novice readers for 200 mammographic examinations (80 cancer cases). Two reading sessions were conducted within 4 weeks. The readers rated the likelihood of malignancy (range, 1-7) and the percentage probability of malignancy (range, 0-100%), with and without AI assistance. Differences in AUROC, sensitivity, and specificity were analyzed., Results: Mean AUROC increased in both novice (0.86 to 0.90 with AI-1 [p = 0.005]; 0.91 with AI-2 [p < 0.001]) and experienced readers (0.87 to 0.92 with AI-1 [p < 0.001]; 0.90 with AI-2 [p = 0.004]). Sensitivities increased from 81.3 to 88.8% with AI-1 (p = 0.027) and to 91.3% with AI-2 (p = 0.005) in novice readers, and from 81.9 to 90.6% with AI-1 (p = 0.001) and to 87.5% with AI-2 (p = 0.016) in experienced readers. Specificity did not decrease significantly in both novice (p > 0.999, both) and experienced readers (p > 0.999 with AI-1 and 0.282 with AI-2). There was no significant difference in the performance change depending on the type of AI software (p > 0.999)., Conclusion: Commercial AI software improved the diagnostic performance of both novice and experienced readers. The type of AI software used did not significantly impact performance changes. Further validation with a larger number of cases and readers is needed., Clinical Relevance Statement: Commercial AI software effectively aided mammography interpretation irrespective of the experience level of human readers., Key Points: • Mammography interpretation remains challenging and is subject to a wide range of interobserver variability. • In this multi-reader study, two commercial AI software improved the sensitivity of mammography interpretation by both novice and experienced readers. The type of AI software used did not significantly impact performance changes. • Commercial AI software may effectively support mammography interpretation irrespective of the experience level of human readers., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC)., Methods: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM)., Results: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant., Conclusion: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In recognition of the distinct clinical challenges and research gaps in young breast cancer (YBC) patients, we established the Comprehensive Young Age Breast Cancer (CHARM) registry to collect prospective data., Methods: This prospective cohort included patients who were newly diagnosed with histologically confirmed breast cancer without prior treatment at the Samsung Medical Center (SMC) in April 2013. We included patients who were either 40 years old or younger at the time of diagnosis, pregnant at breast cancer diagnosis or diagnosed with breast cancer within 1 year of delivery. All data were collected using Medidata's Rave Electronic Data. Clinical data were obtained from electronic medical records. Two experienced pathologists reviewed the pathologic data. Bone mineral densitometry tests have been conducted annually. To obtain multi-omics data, tumor tissues and blood samples were prospectively collected from consenting patients in the registry during surgery. The fertility-related factor also collected collaborated with the Department of Obstetrics and Gynecology. Anti-Müllerian hormone, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were measured using an additional blood sample from baseline to last follow-up. Patient-reported outcomes were assessed using mobile questionnaires., Results: A total of 1868 participants were included in the SMC YBC study. The average (standard deviation) age was 35.57 (3.79) and 99.8% of the participants were premenopausal. Among them, 1062 participants completed the PRO questionnaires., Conclusions: The SMC YBC cohort serves as a comprehensive registry for YBC to optimize care and improve knowledge regarding the management of YBC., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Opinion Statement: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life., (© 2024. The Author(s).)

The prognostic role of the recurrence score (RS) based on the 21-gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21-gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer-free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95-3.73], P = .069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49-5.82], log-rank P < .001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log-rank P = .51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years., (© 2023 UICC.)

Purpose: To estimate the diagnostic yield (DY) of abdominal staging CT for detecting breast cancer liver metastasis (BCLM) in patients with initially diagnosed breast cancer and to determine the indications for abdominal staging CT., Methods: Patients with newly diagnosed breast cancer who underwent abdominal CT as an initial staging work-up between January 2019 and December 2020 were retrospectively analyzed. DY was calculated and analyzed according to patient age, type of treatments, histologic type, histologic grade, lymphovascular invasion, Ki-67 status, hormone receptor status, subtype, and the American Joint Committee on Cancer anatomical staging., Results: A total of 2056 patients (mean age, 51 ± 11 years) were included. The DY of abdominal staging CT for detecting BCLM was 1.1 % (22 of 2056). DY was significantly higher in stage III than in stage I or II cancers (3.9 % [18 of 467] vs. 0 % [0 of 412] or 0.4 % [4 of 1158], respectively, p < .001), and in human epidermal growth factor receptor-2 (HER2)-enriched cancers than in luminal or triple negative cancers (2.9 % [16 of 560] vs. 0.4 % [4 of 1090] or 0.5 % [2 of 406], respectively, p < .001)., Conclusions: The DY of abdominal staging CT for detecting BCLM was low among all patients with initially diagnosed breast cancer. However, although abdominal staging CT for detecting BCLM is probably unnecessary in all patients, it can be clinically useful in patients with stage III or human epidermal growth factor receptor-2-enriched breast cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: MammaPrint assigns chemotherapeutic benefits to patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and 1 to 3 node-positive invasive breast cancer. However, its cost and time-consuming nature limit its use in certain clinical settings. We aimed to develop and validate the prediction models for the low MammaPrint risk group using clinicopathologic and MRI features., Patients and Methods: Overall, 352 women with ER-positive, HER2-negative, and 1 to 3 node-positive invasive breast cancer were retrospectively reviewed and assigned to development (n = 235) and validation sets (n = 117). Univariate and multivariate analyses identified features associated with the low MammaPrint risk group. The area under the receiver operating characteristic curves (AUROCs) of models based on clinicopathologic, MRI, and combined features were evaluated., Results: Development set multivariate analysis showed that clinicopathologic features including low histologic grade (odds ratio [OR], 5.29; P = .02), progesterone receptor-positivity (OR, 3.23; P = .01), and low Ki-67 (OR, 6.05; P < .001) and MRI features, including peritumoral edema absence (OR, 2.24; P = .04) and a high proportion of persistent components (OR, 1.15; P = .004) were significantly associated with the low MammaPrint risk group. The AUROCs of models based on clinicopathologic, MRI, and combined features were 0.77, 0.64, and 0.80 in the development and 0.66, 0.60, and 0.70 in the validation sets, respectively., Conclusion: The combined model incorporating clinicopathologic and MRI features showed potential in predicting the low MammaPrint risk group, and may support decision-making in clinical settings with limited access to MammaPrint., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au 3+ coordination), cellular glutathione depletion, and O 2 production from cellular H 2 O 2 . ICG can generate singlet oxygen from O 2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers., Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers., Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023., Exposure: Pregnancy after breast cancer., Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes., Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival., Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival., Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI)., Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm² was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive. The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC)., Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4-79.9), 90.8% (95% CI: 85.6-94.2), and 83.5% (95% CI: 78.6-87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8-97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9-89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1-79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52-0.63) before training and 0.68 (95% CI: 0.62-0.74) after training, with a difference of 0.11 (95% CI: 0.02-0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69-0.74) before training and 0.79 (95% CI: 0.76-0.80) after training ( P = 0.002)., Conclusion: Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI., Competing Interests: Vivian Youngjean Park and Woo Jung Choi, the editor board member of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. All authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Background: The World Health Organization's fifth edition of tumor series classification was published in 2019 and adopted the term 'Neuroendocrine neoplasm (NEN)' to encompass all tumor classes with predominant neuroendocrine differentiation (NED). Based on the updated classification of the NEN, we conducted a case series using the Clinical Data Warehouse platform of SMC., Methods: In this retrospective study, breast NENs and invasive breast carcinomas no special type (IBCNST) with NED, were defined as 'NENS'. Based on pathology slide findings, a pathologist reclassified the diagnoses. Clinical presentation, tumor characteristics, and clinical outcomes of breast 'NENS' were reviewed retrospectively., Results: A total of 34,370 patients were diagnosed with breast cancer from 1995 to 2022 in SMC, and 14 (0.04 %) patients were diagnosed with breast 'NENS': eight NECs, three NETs, and three IBCNST with NED. The patients' median age was 48.5 years. All patients were treated with curative intent surgery; five patients received neoadjuvant chemotherapy, twelve patients received radiotherapy, six patients received adjuvant chemotherapy, and eight patients received hormone therapy. The median follow-up period for the eight patients with breast NEC was 20.4 months. The median disease-free and overall survival were 14.2 months and 23.6 months, respectively. Patients with NET or IBCNST with NED (n = 6) had an overall favorable outcome, with no deaths, with only one case of disease recurrence., Conclusion: The incidence of primary breast NENS' was very low (0.04 %) in this single-center study. Among them, primary breast NEC was associated with poor overall survival. Novel treatments are thus required to improve the prognosis of primary breast NEC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND)., Methods: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed., Results: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3-4 tumor. In the subgroup analysis, we showed that in the T1-2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group., Conclusion: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Metastatic breast cancer refractory to anthracycline and taxanes often shows rapid progression. The development of effective and tolerable combination regimens for these patients is needed. This phase II trial investigated the efficacy of pemetrexed plus vinorelbine in patients with metastatic breast cancer., Methods: This randomized, open-label, phase II trial was conducted in 17 centers in Korea. Patients with advanced breast cancer who had previously been treated with anthracyclines and taxanes were randomly assigned in a 1:1 ratio to receive either vinorelbine or pemetrexed plus vinorelbine. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included the objective response rate, overall survival, safety, and quality of life., Results: Between March 2017 and August 2019, a total of 125 patients were enrolled. After a median follow-up duration of 14.1 months, 118 progression events and 88 death events had occurred. Sixty-two patients were assigned to the pemetrexed plus vinorelbine arm, and 63 were assigned to the vinorelbine arm. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine (5.7 vs. 1.5 months, p < 0.001). The combination arm had higher disease control rate (76.8% vs. 45.9%, p = 0.001) and a tendency toward longer overall survival (16.8 vs. 10.5 months, p = 0.102). Anemia was more frequent in the pemetrexed plus vinorelbine arm per cycle compared with vinorelbine (7.9% vs. 1.9%, p < 0.001), but there was no difference in the incidence of grade 3-4 neutropenia per cycle between the pemetrexed plus vinorelbine arm and the vinorelbine single arm (14.7% vs. 19.5%, p = 0.066)., Conclusions: This phase II study showed that pemetrexed plus vinorelbine led to a longer PFS than vinorelbine. Adverse events of pemetrexed plus vinorelbine were generally manageable., Competing Interests: Declaration of Competing Interest S-A Im received research fund from AstraZeneca, Boryung Pharm, Daewoong Pharm, Eisai, Pfizer, and Roche outside of the current work and have been work as advisory board for AstraZeneca, Amgen, Bertis, Eisai, GSK, Hanmi Corp., Lilly, MSD, Novartis, Pfizer, and Roche outside of the current work. Keun Seok Lee has consulting or advisory role for AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, Everest Medicine, Bixink, Daiichi Sankyo, and Roche; has received research funding from Novartis; has received research drug supply from Dong-A ST. All remaining authors have declared no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study., Materials and Methods: Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes., Results: The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis., Conclusion: In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

Importance: Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients., Objective: To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery., Design, Setting, and Participants: This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years)., Main Outcomes and Measures: The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status., Results: A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group)., Conclusions and Relevance: In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Aim: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations., Methods: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m 2 ) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated., Results: Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression ≥1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs., Conclusion: Nivolumab plus eribulin showed promising efficacy and tolerable safety in previously treated HER2- metastatic BC., Trial Registration: NCT04061863., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ono Pharmaceutical Co. provided the study drug (nivolumab) and provided funding to Seoul National University Bundang Hospital for study conduct. Eisai Korea inc. provided the study drug (eribulin) for study conduct. The companies were not involved in trial data analysis and manuscript writing. SHK has a consulting or advisory role with Ono Pharmaceutical. SI reports receiving research grant from AstraZeneca, Daewoong Pharm, Eisai, Roche, and Pfizer and personal consultation fees from AstraZeneca, Eisai, GSK, Hanmi, Lilly, MSD, Idience, Novartis, Roche, and Pfizer. The research group received drugs from Eisai and Boryung. KL reports receiving honorarium from AstraZeneca, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, Roche. JS reports receiving research funding from MSD, Roche, Novartis, Lilly, Pfizer, Daiichi Sankyo, AstraZeneca, GlaxoSmithKline, Sanofi, and Boehringer Ingelheim. KHP has a consulting or advisory role with Eisai, Eli Lilly, Novartis, Daiichi Sankyo/Astra Zeneca, Pfizer, IMBDx, Celltrion and Roche and has received research funding from Astra Zeneca. JHK has a consulting or advisory role with Bixink, Eisai, Yuhan, Novartis, Daiichi Sankyo/Astra Zeneca, Pfizer, and Roche and has received research funding from Ono Pharmaceutical and Roche. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We investigated the effects of sevoflurane exposure on the expression of matrix metalloproteinase (MMP), expression and ablation of natural killer group 2, member D (NKG2D) ligands (UL16-binding proteins 1-3 and major histocompatibility complex class I chain-related molecules A/B), and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells., Methods: Three human breast cancer cell lines (MCF-7, MDA-MB-453, and HCC-70) were incubated with 0 (control), 600 (S6), or 1200 μM (S12) sevoflurane for 4 h. The gene expression of NKG2D ligands and their protein expression on cancer cell surfaces were measured using multiplex polymerase chain reaction (PCR) and flow cytometry, respectively. Protein expression of MMP-1 and -2 and the concentration of soluble NKG2D ligands were analyzed using western blotting and enzyme-linked immunosorbent assays, respectively., Results: Sevoflurane downregulated the mRNA and protein expression of the NKG2D ligand in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells but did not affect the expression of MMP-1 or -2 or the concentration of soluble NKG2D ligands in the MCF-7, MDA-MB-453, and HCC-70 cells. Sevoflurane attenuated NK cell-mediated cancer cell lysis in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells (P = 0.040, P = 0.040, and P = 0.040, respectively)., Conclusions: Our results demonstrate that sevoflurane exposure attenuates NK cell-mediated cytotoxicity in breast cancer cells in a dose-dependent manner. This could be attributed to a sevoflurane-induced decrease in the transcription of NKG2D ligands rather than sevoflurane-induced changes in MMP expression and their proteolytic activity.

The internal mammary lymph nodes (IMLNs) are a main pathway of metastasis in breast cancer, and breast magnetic resonance imaging (MRI) plays an important role in staging that disease. We investigated the MRI parameters that can predict metastatic IMLNs and evaluated their diagnostic performance by comparing the breast MRI findings for metastatic and benign IMLNs. From January 2016 to December 2020, 474 cases of enlarged IMLNs on breast MRI were identified. By cytopathology or integrated positron emission tomography/computed tomography (PET/CT), 168 IMLNs were confirmed as metastatic, and 81 were confirmed as benign. Breast MRIs were reviewed by 2 radiologists, and various parameters (node axes, fatty hilum, necrosis, margin characteristics, restricted diffusion, and involved levels; primary tumor location and skin involvement) were assessed. Independent t-tests, receiver operating characteristic (ROC) curve analyses, chi-square tests, and Fisher exact tests were performed to compare and evaluate the diagnostic accuracy of the imaging findings. Significant differences in the breast MRI findings for the short and long axes, fatty hilum, necrosis, margin characteristics, diffusion restriction, and tumor location were observed between benign and metastatic IMLNs. Compared with the long axis and the ratio of the axes, the short axis had the best diagnostic value (higher area under the ROC curve) for predicting metastatic IMLNs. In conclusion, breast MRI parameters such as short axis, presence of fatty hilum, necrosis, margin characteristics, and diffusion restriction can be used to evaluate and differentiate benign from metastatic IMLNs, offering valuable insights to improve diagnosis and treatment planning in breast cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: The disparate prognostic implications between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have been demonstrated. However, information on premenopausal patients remains insufficient., Objective: To examine long-term survival outcomes of ILC and IDC in premenopausal patients using national databases., Design, Setting, and Participants: This cohort study used the Surveillance, Epidemiology, and End Results (SEER), Korean Breast Cancer Registry (KBCR), and Asan Medical Center Research (AMCR) databases to identify premenopausal patients with stage I to III ILC or IDC between January 1, 1990, and December 31, 2015. The median follow-up time was 90 (IQR, 40-151) months in the SEER database, 94 (IQR, 65-131) months in the KBCR database, and 120 (IQR, 86-164) months in the AMCR database. Data were analyzed from January 1 to May 31, 2023., Main Outcomes and Measures: The primary outcome was breast cancer-specific survival (BCSS), which was analyzed according to histological type, and the annual hazard rate was evaluated. Survival rates were analyzed using a log-rank test and a Cox proportional hazards regression model with time-varying coefficients. Multivariable analysis was performed by adjusting for tumor characteristics and treatment factors., Results: A total of 225 938 women diagnosed with IDC or ILC and younger than 50 years were identified. Mean (SD) age at diagnosis was 42.7 (5.3) years in the SEER database, 41.8 (5.5) years in the KBCR database, and 41.8 (5.5) years in the AMCR database. In terms of race (available for the SEER database only), 12.4% of patients were Black, 76.1% were White, 11.0% were of other race (including American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), and 0.5% were of unknown race). Patients with ILC had better BCSS in the first 10 years after diagnosis than those with IDC (hazard ratios [HRs], 0.73 [95% CI, 0.68-0.78] in the SEER database, 1.20 [95% CI, 0.91-1.58] in the KBCR database, and 0.50 [95% CI, 0.29-0.86] in the AMCR database), although BCSS was worse after year 10 (HRs, 1.80 [95% CI, 1.59-2.02] in the SEER database, 2.79 [95% CI, 1.32-5.88] in the KBCR database, and 2.23 [95% CI, 1.04-4.79] in the AMCR database). Similar trends were observed for hormone receptor-positive tumors (HRs, 1.55 [95% CI, 1.37-1.75] in the SEER database, 2.27 [95% CI, 1.01-5.10] in the KBCR database, and 2.12 [95% CI, 0.98-4.60] in the AMCR database). Considering the annual hazard model of BCSS, IDC events tended to decline steadily after peaking 5 years before diagnosis. However, the annual peak event of BCSS was observed 5 years after diagnosis for ILC, which subsequently remained constant., Conclusions and Relevance: These findings suggest that premenopausal women with ILC have worse BCSS estimates than those with IDC, which can be attributed to a higher late recurrence rate of ILC than that of IDC. Histological subtypes should be considered when determining the type and duration of endocrine therapy in premenopausal women.

Importance: The number of patients with breast cancer who have children is substantial. However, the emotional burden of this disease and its implication for childhood development remain largely unknown., Objective: To investigate the clinical factors in parenting stress in mothers with breast cancer and the association of maternal depression and parenting stress with their children's emotional development., Design, Setting, and Participants: This cross-sectional study involved a survey of females with stage 0 to 3 breast cancer and was conducted from June 2020 to April 2021 in Seoul, South Korea. Participants were aged 20 to 45 years and completed the Center for Epidemiologic Studies Depression-Revised scale and basic questionnaires on demographic and clinical characteristics. Participants with children completed the Korean Parenting Stress Index Short Form (K-PSI-SF), Child Behavior Checklist, Junior Temperament and Character Inventory, and Children's Sleep Habits Questionnaire., Exposure: Having children in patients with breast cancer., Main Outcomes and Measures: Multivariable logistic and linear regression analyses were performed to investigate the association between maternal depression and parenting stress., Results: A total of 699 females (mean [SD] age, 39.6 [4.6] years) were included, of whom 499 had children (mean [SD] age of children, 8.0 [2.7] years). Depression was more common in patients with children (odds ratio [OR], 2.25; 95% CI, 1.01-5.05) and patients who had gonadotropin-releasing hormone treatment (OR, 1.68; 95% CI, 1.15-2.44). Disease duration was inversely associated with depression (OR, 0.85; 95% CI, 0.76-0.96). Cancer-related factors were not associated with the K-PSI-SF score. Having children aged 6 years or older (β = 3.09; 95% CI, 0.19-5.99); being the sole primary caregiver (β = -3.43; 95% CI, -5.87 to -0.99); and reporting certain temperament (eg, novelty seeking: β = 0.58; 95% CI, 0.46-0.71), emotional problems (eg, anxious/depressed: β = 8.09; 95% CI, 3.34-12.83), and sleeping pattern (eg, bedtime resistance: β = 0.57; 95% CI, 0.15-0.99) subscale scores in their children were associated with parenting stress. Depression and parenting stress were correlated (β = 0.56; 95% CI, 0.45-0.66; P < .001). The emotional challenges encountered by children of mothers with breast cancer were not significantly different from reference values., Conclusions and Relevance: This study found that in patients with breast cancer, child-related factors and depression were significantly associated with parenting stress, but breast cancer-related factors were not correlated. The findings suggest that mothers with breast cancer are susceptible to both depression and parenting stress and that tailored counseling and support are needed.

Background: This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method. To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM)., Methods: The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values., Results: In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods., Conclusions: NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes., (© 2023. Society of Surgical Oncology.)