Purpose: Exosome-surface enhanced Raman spectroscopy-artificial intelligence platform (exosome-SERS-AI) is an innovative liquid biopsy method that acquires SERS signals from plasma exosomes and analyzes them using deep learning models to diagnose cancer. This study aimed to evaluate whether exosome-SERS-AI could increase the diagnostic accuracy of ultrasonography (US) for suspicious breast lesions. Methods This prospective multicenter study enrolled 500 patients between November 2024 and December 2025. Eligible participants will be women aged ≥ 40 years who will undergo US performed by specialized breast radiologists and have suspicious breast lesions assigned to a Breast Imaging Reporting and Data System (BI-RADS) category 3–5 assessment. A 6 mL whole blood sample was collected from each participant. After plasma separation, SERS, which is highly sensitive to exosomes, was employed to measure Raman signals, and the acquired data were processed using artificial intelligence algorithms. Following sampling, all patients underwent US-guided core needle biopsy for breast lesions classified as BI-RADS category 4 and 5, and 12-months of follow-up US for lesions classified as BIRADS category 3. Histopathological examination was used as the reference standard for BIRADS 4 and 5 lesions, whereas stability on 12-month follow-up US was used as the reference standard for BI-RADS 3 lesions. The cohort is expected to have an equal distribution of benign and malignant cases. The following outcome measures were compared between US alone and the combination of exosome-SERS-AI with US: sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve. Enrollment is expected to be completed by 2025, and the study results are expected to be presented in 2026.Discussion: This prospective multicenter study will evaluate the performance of exosome-SERSAI compared to US in women with BI-RADS categories 3–5. Participant enrollment is ongoing.

Survival rates of breast cancer, which is the most common cancer among women, continue to improve. Diet after diagnosis has become an area of interest regarding breast cancer survival, and evidence has accumulated over past decades. Although earlier studies did not offer recommendations beyond general cancer prevention guidelines, more recent findings suggest a potential role of dietary factors in breast cancer prognosis. Healthy dietary patterns have been associated with reduced mortality from non-breast cancer causes. However, associations with breast cancer-specific mortality were less consistent in cohort studies of survivors, most of which were conducted in Western populations. Two randomized intervention trials on the effect of low-fat dietary patterns yielded inconsistent findings, with one study reporting a lower risk of breast cancer recurrence and the other showing no association. Because reduced fat intake is often accompanied by weight loss and increased intake of other dietary components, such as higher vegetable consumption, these factors need to be considered when interpreting the results. Both soy food and dietary fiber intakes have been shown to reduce the risk of all-cause mortality after breast cancer diagnosis. High circulating vitamin D levels may confer benefits, particularly among women with suboptimal vitamin D status. However, the current evidence does not support the protective effect of other individual micronutrients or dietary supplements. Sugar and carbohydrate intake, and coffee consumption remain areas of emerging research interest. In addition, the role of dietary factors should be investigated in specific subgroups, such as premenopausal women, users of antihormone therapy, and those with estrogen receptor-positive or -negative tumors.Importantly, most associations were observed predominantly in Western or postmenopausal populations and may not be generalizable to Asian or younger women. Further studies are needed to clarify the population-specific effects and strengthen the evidence base for dietary recommendations for breast cancer survivors.

Purpose: Langer's axillary arch (LAA) is a common muscular variant that may affect the assessment of axillary lymph nodes in breast cancer. We investigated whether the presence of the LAA had a meaningful clinical impact in a large cohort of Korean patients with breast cancer. Methods: The medical records and imaging of 2,904 patients (2,953 cases) who underwent axillary surgery for breast cancer were reviewed. The presence of LAA was determined using chest computed tomography scans. The number of retrieved lymph nodes, the accuracy of axillary ultrasonography, and survival outcomes were compared between the LAA and nonLAA groups. Results: The LAA muscle was identified in 301 patients (10.2%). Preoperative ultrasound evaluation showed a lower specificity in the LAA group (77.9% vs. 83.6%, p = 0.031).Additionally, invasive disease-free survival (iDFS) was significantly worse in the ‘LAA-positive patients’ after adjusting for stage, histologic grade, and treatment (adjusted hazard ratio, 2.00; 95% confidence interval, 1.00–4.01; p = 0.048), with regional axillary recurrence being notably more frequent in patients with the LAA muscle (p = 0.005). Conclusion The presence of the LAA muscle was associated with reduced specificity on preoperative ultrasound. Patients with LAA muscle-associated tumors had worse iDFS, with regional axillary recurrence occurring more frequently. Recognition of the LAA muscle during axillary staging and surgery may improve nodal assessment accuracy and outcomes, especially in the era of axillary surgery de-escalation.

In breast cancer, sentinel lymph nodes (SLNs) represent the first site of interaction between tumor-derived antigens and the host immune system. However, descriptive data on immune cell subsets within the SLN remains limited. This exploratory study evaluated immune cell populations in SLN samples from women with invasive breast cancer (IBC) using flow cytometry, and assessed their distribution according to clinicopathological characteristics.SNL scrapings were collected from 22 patients with IBC. SNL cells were evaluated using flow cytometry, and the results were compared with clinical and pathological variables, such as tumor subtype, axillary status, lymphovascular invasion (LVI), histological grades, and expression of estrogen receptors (ERs) and human epidermal growth factor receptor 2 (HER2). The frequencies of monocytes and neutrophils were not significantly correlated with the clinical variables analyzed. In patients with LVI, there was an increase in the frequency of CD4+ T cells and programmed death-1 (PD-1) expression in CD8+ T-cells.Furthermore, a reduction in central memory CD4+ T cells and an increase in terminal effector memory CD4+ T cells were observed in patients with histological grade III disease compared to those with histological grade I disease. It was also observed that in patients expressing ERs and HER2, there was an increase in PD-1 and programmed death-ligand 1 expression in CD8+ T-cells. These findings provide a descriptive overview of immune cell distribution in SLNs according to their clinicopathological features. These results are preliminary and hypothesis-generating, supporting the need for larger longitudinal studies to further characterize the immune profiles within tumor-draining lymph nodes.

Ado-trastuzumab emtansine (T-DM1) is an effective adjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer; however, its surgical safety profile remains unclear. We observed delayed bleeding with variable and often subtle clinical manifestations during implant-based breast reconstruction (IBBR). Two patients who received adjuvant T-DM1 therapy after IBBR were retrospectively reviewed. The patient in Case 1 developed a recurrent seroma and liquefied hematoma requiring repeated aspirations, with platelet counts decreasing from 218 × 109 /L to 33 × 109 /L before expander removal.The patient in Case 2 experienced an acute massive hematoma on postoperative day (POD) 2, prior to T-DM1 initiation, which resolved after re-exploration; a temporally distinct delayed hemorrhagic event occurred on POD 175 during T-DM1 therapy after radiotherapy, accompanied by a platelet nadir of 34 × 109 /L. Both patients required plateletpheresis and prolonged drainage. Delayed bleeding during T-DM1 therapy may reflect a combination of hematological suppression and vascular vulnerability. Therefore, vigilant surveillance and cautious postoperative rehabilitation are warranted.

Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. Conclusion This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Purpose: Based on the KEYNOTE-522 study, neoadjuvant pembrolizumab plus chemotherapy has become the standard treatment for early-stage triple-negative breast cancer (TNBC).This study evaluated the real-world efficacy, safety, and predictors of pathologic complete response (pCR) in Korean patients. Methods: We conducted a retrospective cohort study of 174 patients with early-stage TNBC who received the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin and cyclophosphamide) at a tertiary cancer center between August 2022 and July 2024. We assessed the primary endpoints, including pCR rate and event-free survival (EFS). We performed univariable and multivariable logistic regression analyses to identify independent predictors of pCR. Results: The median patient age was 50 years (range, 24–74 years). The clinical stages were II and III in 79.3% and 20.1% of patients, respectively, and 10.9% had clinical N3 disease. The overall pCR rate was 62.1%, and the N3 subgroup had a pCR rate of 47.4%. On multivariable analysis, high baseline Ki-67 expression (≥ median, 75%) was significantly associated with pCR (odds ratio, 2.84; 95% confidence interval, 1.45 to 5.66; p = 0.002). At a median followup of 18.4 months, the 12-month EFS rate was 97.4%, with significantly superior outcomes observed in patients who achieved pCR compared with those who did not achieve pCR (100% vs. 93.1%, p = 0.007). The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients. Conclusion In this real-world analysis of one of the largest Asian cohorts of patients with earlystage TNBC treated with neoadjuvant pembrolizumab, the KEYNOTE-522 regimen demonstrated substantial efficacy and manageable toxicity, consistent with the original trial findings.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

Angiosarcoma associated with lymphedema is a rare soft tissue malignancy that occurs owing to chronic lymphedema, primarily following breast cancer surgery. We present a case of an 83-year-old female who developed angiosarcoma 14 years after undergoing breast cancer surgery. Diagnosis was confirmed through excisional biopsy, histopathological evaluation, and imaging. Computed tomography and magnetic resonance imaging revealed diffuse dermal thickening with an enhanced subcutaneous nodular lesion on the right arm. This unusual case emphasizes the importance of vigilant monitoring in patients with chronic lymphedema post-breast cancer surgery, as early radiologic and clinical detection can facilitate timely intervention and improve outcomes.