PURPOSE: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in 40%-70% of women with breast cancer. These patients may not need surgery as all local tumor has already been eradicated by NST. However, nonsurgical approaches, including imaging or vacuum-assisted biopsy (VAB), were not able to accurately identify patients without residual cancer in the breast or axilla. We evaluated the feasibility of a machine learning algorithm (intelligent VAB) to identify exceptional responders to NST.METHODS: We trained, tested, and validated a machine learning algorithm using patient, imaging, tumor, and VAB variables to detect residual cancer after NST (ypT+ or in situ or ypN+) before surgery. We used data from 318 women with cT1-3, cN0 or +, human epidermal growth factor receptor 2–positive, triple-negative, or high-proliferative Luminal B–like breast cancer who underwent VAB before surgery (ClinicalTrials.gov identifier: NCT02948764 , RESPONDER trial). We used 10-fold cross-validation to train and test the algorithm, which was then externally validated using data of an independent trial (ClinicalTrials.gov identifier: NCT02575612 ). We compared findings with the histopathologic evaluation of the surgical specimen. We considered false-negative rate (FNR) and specificity to be the main outcomes.RESULTS: In the development set (n = 318) and external validation set (n = 45), the intelligent VAB showed an FNR of 0.0%-5.2%, a specificity of 37.5%-40.0%, and an area under the receiver operating characteristic curve of 0.91-0.92 to detect residual cancer (ypT+ or in situ or ypN+) after NST. Spiegelhalter's Z confirmed a well-calibrated model ( z score –0.746, P = .228). FNR of the intelligent VAB was lower compared with imaging after NST, VAB alone, or combinations of both.CONCLUSION: An intelligent VAB algorithm can reliably exclude residual cancer after NST. The omission of breast and axillary surgery for these exceptional responders may be evaluated in future trials.
Axillary ultrasound (AUS) is a standard procedure in the preoperative clinical identification of axillary metastatic lymph node (LN) involvement. It guides decisions about local and systemic therapy for patients with early breast cancer (EBC). But there is only weak evidence on the diagnostic criteria and standard interpretation. The aim of this study was to assess the performance of AUS in the detection and exclusion of LN metastases. In a retrospective single-center study, 611 consecutive EBC patients with 622 axillae underwent AUS +/- core needle biopsy (CNB) plus axillary surgery, i.e. sentinel lymph node biopsy and/or axillary lymph node dissection. For all patients, AUS image documentation of at least the most suspicious LN was saved during the initial diagnostic work-up. The diagnostic outcome measures were sensitivity, specificity, accuracy, Youden-index (YI), and diagnostic odds ratio (DOR) on the basis of the daily routine interpretation and on the basis of previously recommended diagnostic criteria by two blinded examiners. On the basis of the daily routine interpretation, AUS had a sensitivity (95 % CI) of 53.3 % (46.4-60.1), a specificity (95 % CI) of 93.6 % (90.8-95.8), an accuracy (95 % CI) of 79.7 % (76.4-82.8), a YI (95 % CI) of 0.47 (0.40 - 0.54), and a DOR (95 % CI) of 16.75 (10.37-27.05). Systematic application of previously recommended diagnostic criteria did not improve the diagnostic accuracy of routinely interpreted AUS. AUS performance alone is not sufficient to accurately identify or exclude axillary metastatic disease in unselected patients with EBC.
Objective: This retrospective cohort study compares surgical outcomes among patients with endometrial carcinoma (EC) after the implementation of a robotic-assisted (RA) surgical program at a tertiary care center. Methods: A total of 122 EC patients who underwent surgery between March 2022 and February 2025 were included. Patients were divided into two cohorts based on the implementation of RA surgery: Group 1 (March 2022–August 2023) and Group 2 (September 2023–February 2025). Data collected included demographics, surgical approach, operative time, hospital stay, completion of staging procedures, and 30-day postoperative complications. Results: RA laparoscopy was used predominantly in Group 2, replacing conventional laparoscopy (CL). Laparotomy was significantly less frequent in group 2 (11.9% vs. 36.4%; p < 0.001). Among patients with FIGO stage I, all patients underwent minimally invasive surgery (MIS) in Cohort 2 (100% vs. 71.9%; p < 0.001). Median hospital stay was significantly shorter in Group 2 (3 days vs. 4 days; p < 0.001). A 30-day mortality occurred in one patient (n = 1) within the total study cohort (0.82%) and was attributed to pulmonary embolism on postoperative day 14 after RA laparoscopy. Rates of Grade ≥3 postoperative complications were similar (7.3% vs. 7.5%), as were wound complications (5.5% vs. 3%). The use of sentinel lymph node (SLN) mapping increased significantly in Group 2 (91% vs. 54.5%; p < 0.001). Completion staging procedures were significantly reduced in group 2 (9.1% vs. 0%; p = 0.017). Conclusions: The integration of RA laparoscopy significantly reduced laparotomy rates and hospital stays while increasing SLN mapping. These results support the continued adoption of RA laparoscopy to enhance MIS and improve patient outcomes.
Adenomyosis, a prevalent gynecologic condition involving invasion of endometrial tissue into the myometrium, remains poorly understood in terms of its molecular pathogenesis. Numb, an important regulator of cellular destiny and stem cell maintenance, has been implicated in numerous proliferative diseases; however, the role for Numb in adenomyosis has not yet been investigated. This research examines the degree to which Numb protein may play a role in the pathogenesis of adenomyosis and additional invasive endometrial diseases. This study analyzed Numb protein expression in tissues from 21 adenomyosis patients and 14 controls using immunohistochemistry. Numb levels were evaluated in eutopic endometrium, ectopic lesions, and myometrium. Additionally, comprehensive bioinformatics analyses were performed including TCGA expression analysis, STRING protein–protein interaction network analysis, and Kaplan–Meier survival analysis to elucidate the clinical significance and mechanistic role of NUMB in endometrial pathology linked to invasive growth. Compared to controls (p < 0.001), adenomyosis patients’ eutopic endometrium and myometrium showed considerably higher levels of numb expression. It was predominantly observed in single cells rather than clusters. No significant variation was noted across menstrual cycle phases. Elevated Numb levels in the myometrium suggest a potential role in tissue invasion. TCGA analysis revealed significant associations between NUMB alterations and expression patterns in endometrial carcinoma, with copy number alterations showing a dose-dependent relationship with the expression levels. STRING network analysis identified NUMB as a central hub protein with 20 high-confidence interactions, particularly enriched in Notch signaling pathway components (FDR = 1.0 × 10−15). Kaplan–Meier survival analysis demonstrated that endometrial carcinoma patients with NUMB alterations had significantly better overall survival compared to unaltered cases (p = 9.119 × 10−3), with 92% vs. 73% survival at 100 months. This study presents new evidence of elevated Numb expression in adenomyosis, suggesting that it may play a part in the pathophysiology of the disease and that it is a useful marker for dysregulation of endometrial stem cells. The comprehensive bioinformatics analyses establish NUMB as a central regulator of endometrial homeostasis with significant prognostic value in endometrial malignancies, providing mechanistic insights into the pathogenesis of invasive endometrial diseases and identifying potential therapeutic targets.
6 September 2025 in Breast Cancer: Basic and Clinical Research
Juvenile fibroadenoma typically is seen in the adolescent patient and has distinctive clinical and histopathological features that are related to the early onset of the benign tumor. Only rarely can juvenile fibroadenoma occur as a prepubertal lesion or may be detected earlier in childhood, raising questions about differential diagnosis and management of the lesion. We present a case of very early first manifestation of juvenile fibroadenoma in a 2-year-old patient. Under clinical observation and conservative management over a 7-year period, there was no progression. At the age of 9 years, rapid growth of the lesion occurred causing clinical symptoms. Complete surgical excision resulted in a good clinical outcome. Histologically, the diagnosis of juvenile fibroadenoma was made. In summary, juvenile fibroadenoma is the most common breast neoplasia in adolescents and may cause excessive unilateral growth resulting in gross asymmetry and pain. However, it can be detectable in early childhood and after a dormant period of several years, as in this case, lead to sudden massive growth at the onset of puberty. The clinical management should include an interdisciplinary treatment approach with gynecology, pediatrics, and pediatric surgery to balance the risks and benefits of conservative management. Surgical removal can be safely postponed until it becomes necessary due to clinical symptoms.