The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

Purpose: Radical cystectomy (RC) is associated with substantial postoperative morbidity, and unplanned readmission remains common despite advances in perioperative management. However, the association between postoperative readmission due to complications and oncologic outcomes after RC for bladder cancer has not been clearly defined. We evaluated the impact of postoperative readmission on overall survival (OS) and cancer-specific survival (CSS) after RC for bladder cancer. Materials and Methods: We retrospectively analyzed 3,972 patients who underwent RC for bladder cancer in a multicenter cohort. Postoperative readmission was defined as unplanned hospitalization within 90 days postsurgery due to surgery-related complications. Survival outcomes were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent predictors of OS and CSS. Results: Among the study population, 916 patients (23.1%) experienced postoperative readmission. Baseline and perioperative characteristics were generally comparable between patients with and without readmission. Kaplan-Meier analyses demonstrated significantly worse OS and CSS among patients who experienced postoperative readmission (both log-rank p<0.001). In multivariable analyses adjusting for clinicopathological factors, postoperative readmission remained independently associated with worse OS (hazard ratio [HR], 1.654; 95% confidence interval [CI], 1.464–1.868; p<0.001) and CSS (HR, 1.761; 95% CI, 1.509–2.055; p<0.001). Conclusion Postoperative readmission within 90 days after RC was independently associated with inferior long-term oncologic outcomes. These findings suggest the importance of strategies aimed at preventing postoperative complications and subsequent readmission.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Purpose: Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway. Methods: In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed. Results: Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim. Conclusion Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.

Purpose: Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway. Methods: In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed. Results: Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim. Conclusion Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.