Fondazione IRCCS Istituto Nazionale dei Tumori

Breast surgery is a cornerstone of breast cancer (BC) treatment and has distinctive features that distinguish it from other subspecialties within general surgery. BC management requires multidisciplinary competencies, with specialized training and dedicated care shown to improve patient outcomes. Breast surgery training should become a critical priority within residency programs. We conducted a cross-sectional survey during the 2025 Italian Society of Breast Surgeon (ANISC) annual meeting, to explore the opinions of breast surgery consultants and residentsregarding the current state of breast surgery training, as well as future perspectives for its improvement. A total of 126 participants (77% consultants, 23% residents) completed the survey. Most of the participants (49.2%) worked in medium-volume Breast Units and had > 10 years of clinical practice (45.2%). Overall, 67.5% of respondents judged their training only partially satisfactory, while 23.8% were completely dissatisfied. The majority (58.7%) supported a hybrid model with three years of general surgery followed by two years exclusively dedicated to breast surgery. Most respondents endorsed mandatory training periods in complementary specialties (79.4%) and rotations in peripheral Breast Units (69.8%). Notably, 88.1% favored the development of a vertical breast surgeon profile, capable of independently managing both oncologic and reconstructive procedures. This is the first national survey exploring breast care professionals’ perspectives on surgical training in Italy. Only 8.7% considered the current system adequate to meet clinical needs. The strong demand for structured and specialized programs, together with the recognition of a vertical breast surgeon figure, highlights the urgent need to redefine breast surgery training pathway.

Advanced tumors harboring SWI/SNF mutations are rare and aggressive. Often presenting in young patients, treatment options are limited. This phase II basket study (NCT02601950) assessed oral tazemetostat, an EZH2 inhibitor, at 800 mg twice daily (N = 129). Cohorts included malignant rhabdoid tumors (n = 32, Cohort 1), synovial sarcoma (n = 33, Cohort 2), INI1-negative tumors (n = 32, Cohort 3), renal medullary carcinoma (n = 14, Cohort 4), and poorly differentiated chordoma (n = 18, Cohort 7). Efficacy assessments used a 2-stage Green-Dahlberg design. Stage 1 futility was predefined as objective responses (complete/partial [CR/PR]) <5% (Cohorts 1, 3, 4, 7) or 16-week progression-free survival (PFS) <15% (Cohort 2). Sufficient clinical activity was declared in Stage 2 if ≥5 patients had a CR/PR (Cohorts 1,3,4,7) or ≥9 patients had a CR/PR, or stable disease (Cohort 2; primary endpoints). Responses were observed in malignant rhabdoid tumors (9%; n = 2 PR, n = 1 CR), INI1-negative tumors (9%; n = 3 PR, n = 0 CR), and poorly differentiated chordoma (6%; n = 1 PR, n = 0 CR) but not the remaining 2 cohorts (both 0%). 16-week PFS for synovial sarcoma was 15.2% (n = 5). Grade ≥3 treatment-related adverse events occurred in 10% of patients. Tazemetostat demonstrated preliminary antitumor activity in a subset of poor-prognosis cancers, underscoring the need for combination strategies when EZH2 signaling is not the sole disease driver.

Avelumab, pembrolizumab, and enfortumab vedotin (EV) demonstrated efficacy in mUC following platinum-based chemotherapy. However, real-world data in patients with urothelial carcinoma with squamous differentiation (UCSD) are limited. The aim of this study is to assess the real-world clinical outcomes of avelumab, pembrolizumab, or EV in mUCSD patients. The ARON-2EV study is a retrospective, international, multicenter analysis in patients with mUC treated with avelumab, pembrolizumab, or EV across 79 centers in 21 countries. Patients were divided into three cohorts: 1 (avelumab), 2 (pembrolizumab), and 3 (EV). Primary endpoints were overall survival (OS) and time on treatment (ToT). Secondary objectives included evaluating clinical factors associated with outcomes and exploring the impact of UCSD histology on response to therapy. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and chi-square tests, and Pearson's correlation coefficients. A total of 1918 patients, 1696 with advanced pure UC (pUC) and 222 with mUCSD (36 in cohort 1, 111 in cohort 2, and 75 in cohort 3), were included. Median OS was shorter in patients with UCSD compared to patients with pUC histology in the three cohorts (1: 13.0 vs 26.8months, HR 2.66,p = 0.003; 2: 10.2 vs 18.5months, HR 1.52,p = 0.008; and 3: 7.6 vs 13.1months, HR 1.68,p = 0.011). Median ToT was shorter in patients with UCSD compared to patients with pUC histology in cohort 1 (3.5 vs 5.6months, HR 1.57,p = 0.044) and 3 (7.6 vs 13.6months, HR 1.83,p = 0.005) but not in cohort 2 (3.7 vs 4.7months, HR 1.19,p = 0.177). Response to therapy was negatively correlated with UCSD histology in cohorts 2 (correlation coefficient 0.094,p = 0.008) and 3 (correlation coefficient 0.107,p = 0.021), while response to avelumab was not correlated with UCSD (correlation coefficient 0.072,p = 0.263). UCSD is a histology with a poor prognosis and response to treatments compared to pUC. Treatments activity and effectiveness in divergent differentiations should be addressed in dedicated prospective studies. NCT05290038.

The performance of breast MRI (bMRI) depends on image quality, varying due to patient-related or technical/protocol factors. The resulting artifacts can heavily reduce sensitivity and specificity. We developed a bMRI quality scoring system (bMRI-QUAL) for the bMRI standard protocol. Two independent readers with 3 years of experience evaluated 133 consecutive 1.5-T examinations (sample size calculated to ensure reproducibility). Each sequence was rated on a 4-point scale: 0 = not diagnostic; 1 = relevant artifacts with conserved diagnostic value; 2 = slight artifacts with conserved diagnostic value; 3 = excellent image quality. Each score was weighted in the following formula: (T2-weighted * 1) + (diffusion weighted imaging with b = 0 * 0.5) + (apparent diffusion coefficient maps * 0.5) + (T1-weighted-precontrast * 1) + (T1-weighted-postcontrast * 2) + (T1-weighted-subtracted * 3). This sum was divided by 2.4, obtaining a 0-to-10 global score (GS), with < 6 considered insufficient. The average GS between the two readers was 8.3 ± 1.0, with 102/133 examinations (76.7%) receiving a score ≥ 7 from both readers. Only one case (0.8%) was scored < 6 by both readers. The Bland-Altman analysis showed bias of -0.12, with limits of agreement ranging from -2.52 to +2.29. The difference in GS between the two readers (coverage probability) was 72/133 (54.1%) within ±1 and 123/133 (92.5%) within ±2. Coverage probability within ±1 point ranged from 94.0% to 99.2% across sequences. Average evaluation time/examination was 3 min. bMRI-QUAL is a reproducible quality scoring system. Breast MRI image quality at a tertiary cancer center was good to excellent in approximately 80% of cases. QuestionBreast MRI image quality varies widely and can compromise diagnostic accuracy. A standardized, clinically weighted scoring system is needed to guide repeat-scan decisions and facilitate quality assurance. FindingsIn 133 breast MRIs, the bMRI-QUAL 0-to-10 scoring system proved to be reproducible. Readers assigned a good-to-excellent mean score (8.3) with a 3-min evaluation time. Clinical relevancebMRI-QUAL provides a relatively fast and reproducible evaluation of breast MRI image quality, with each sequence weighted according to its clinical relevance for lesion detection/characterization. It can support decision-making regarding insufficient image quality and facilitate quality assurance protocols.

Metastasis is the leading cause of death in patients with breast cancer (BC), but the mechanisms underlying metastasis formation are still poorly understood. Circulating tumor cells (CTCs) are considered the main seed of metastasis with demonstrated prognostic impact in patients with BC. They are conventionally identified as cells positive for epithelial markers and lacking leukocyte markers. Nonetheless, circulating cells expressing both markers [dual-positive cells (DPcells)] have been reported but poorly investigated. Here, we evaluated, in a cohort of 340 patients with advanced BC, the prognostic impact of DPcells, showing their association with worse survival, particularly in patients with less than five CTCs. Their prognostic value varied among BC subtypes, with greater relevance observed in triple-negative and HER2-positive BC. Moreover, by performing single-cell genomic profiling of DPcells isolated from patients, we detected genomic aberrations in 28 and 93% of analyzed DPcells and CTCs, respectively. In vivo, DPcells were detected only in the blood of immunocompetent but not immunodeficient mice and no differences in the lung metastatic colonization ability of DPcells versus control cancer cells were observed. Our findings highlight the importance of studying this overlooked subpopulation of CTCs as a prognostic biomarker in BC, which might be particularly important in specific BC subtypes. Moreover, our results support the malignancy and metastasis-forming capability of DPcells and underline the need for future studies better defining the origin of these cells.