e13507 Background: Triple negative breast cancer (TNBC) is associated with poor prognosis and complex management, requiring a dedicated and adequate care pathway. To address this need, Fondazione The Bridge and Bridge for Future-University of Pavia, in collaboration with AIOM (Italian Society of Clinical Oncology) and FAVO (Italian Federation of Voluntary Associations in Oncology), developed a patient-centered TNBC Patient Journey (PJ) for the Italian healthcare setting, to provide accessible information to all stakeholders who are not expert in the breast cancer care such as patients (pts), caregivers, patient associations, other healthcare professionals, healthcare managers and politicians. Methods: A multidisciplinary core group of 9 professionals, including a breast oncologist, radiologist, surgeon, geneticist, patient representative, health policy expert and health economist was established. Firstly, they analysed existing guidelines and care pathways present in literature. Secondly, additional professionals (psycho-oncologist, cardio-oncologist, nutritionist, gynaecologist, pathologist, nurse, plastic surgeon, radiation oncologist, general practitioner and specialist in bone, fertility, nuclear medicine, palliative care) from Breast Units (BUs) and pts’ associations were involved through structured interviews to identify best practices. Starting from these interviews, some key statements defining an optimal TNBC care pathway were selected and validated using a modified Delphi process. Besides, a National survey among Italian BUs was performed to assess the relevance of each statement and its real implementation in every BU. Finally, outcomes were translated into a PJ and a Vademecum. Results: From February 2024 to June 2025 the working group developed 2 main documents: a PJ, mainly addressed to pts and caregivers in a less technical language, and a Vademecum containing clinical explanations, best practices and gaps in pts care; this second tool was designed to provide a clear and deep information about the data reported in the PJ. The manuscripts have been enhanced with visual elements and colour images designed to facilitate reading and draw the reader’s attention. Both documents described the ideal journey of pts distinguishing different pathways in relation to BRCA1/2 status mutation (carriers vs non-carriers). The materials were disseminated nationally through online publication on the websites of involved organizations, printed distribution, press events and meetings with policymakers. Conclusions: This initiative highlights the feasibility and value of a multidisciplinary, co-designed approach to develop accessible, patient-centered tools in TNBC care. The PJ supported standardized and informed care while emphasizing the need for adaptable pathways in a rapidly evolving therapeutic landscape.

Breast-conserving surgery (BCS) for non-palpable lesions is technically demanding, often performed by surgical trainees under supervision. Despite extensive literature evaluating localization techniques, only few studies have directly examined the role of surgeon seniority in determining surgical performance in this specific setting. We conducted a retrospective multicenter analysis (LOCALIZATION01 study, NCT05942105) including 3,195 patients who underwent BCS for non-palpable breast lesions between 2016 and 2024 across 12 Breast Units. Four localization techniques were used: wire-guided (WGL), radioguided occult lesion localization (ROLL), magnetic seed localization (MSL), carbon localization (CL). Outcomes included margin status, calculated resection ratio (CRR), operative time, and complications, stratified by surgeon seniority (attending vs resident). Most procedures were performed by attending surgeons (89.3%, n = 2,855) compared to residents (10.7%, n = 340). Margin positivity rates didn't differ significantly across localization techniques (e.g., ROLL 3.7% vs 2.3%, p = 0.30; MSL 9.4% vs 4.4%, p = 0.11, WGL 2.7% vs 5.9 p = 0.16, CL 0% vs 9.6% p = 0.10). Residents achieved better CRR in ROLL procedures (2.0, IQR 3, [1-47] vs 2.8, IQR 5, [1-78], p = 0.006), but had longer operative times, particularly with SLNB (e.g., MSL 60 min, IQR 31, [37-98] vs 55 min, IQR 20, [18-180], p = 0.02). Complication rates were low and comparable between groups. In a supervised setting, surgeon seniority doesn't significantly impact margin status, complication rates, or overall oncologic safety in BCS for non-palpable breast lesions. Localization methods with high reproducibility, such as ROLL and MSL, may mitigate the influence of surgical inexperience. These findings support the safe involvement of trainees in BCS under adequate supervision.

BACKGROUND:The increasing detection of non-palpable breast lesions has made accurate preoperative localization essential to optimize breast-conserving surgery. Although multiple localization methods exist, there is still a lack of robust, large-scale, multicentre evaluations comparing different techniques. METHODS:The LOCALIZATION01 study compares real-world data from 13 breast units in Italy and Switzerland on the impact of localization techniques on breast-conserving surgery for non-palpable lesions between 2016 and 2024. Four localization techniques were compared: wire-guided (WGL), radio-guided (ROLL), magnetic seed (MSL), and carbon (CL). The main outcomes were margin status, calculated resection ratio, postoperative complications, and surgical time. Subgroup analyses were performed for body mass index, lesion morphology and histopathology. RESULTS:In total, 3241 patients were enrolled (ROLL 985, MSL 592, WGL 1079, and CL 585). ROLL achieved the highest rate of negative surgical margins, significantly outperforming MSL, WGL, and CL (97.5% versus 94.7% versus 94.5% versus 90.6%, respectively; P < 0.05). CL was associated with the highest postoperative complications rate (16.7%) versus ROLL (4.1%), MSL (4.5%), and WGL (2.1%) (P < 0.0001). The surgical time for MSL was significantly shorter when compared with WGL (46 versus 70 minutes (min); P < 0.0001) and CL (55 min; P < 0.0001). WGL had the most favourable calculated resection ratio (2.4), followed by MSL (2.6), ROLL (2.7), and CL (3.0). Multivariable analysis identified CL as an independent predictor of positive margins (odds ratio 1.82; P = 0.004), whereas ROLL was protective (odds ratio 0.45; P = 0.009). CONCLUSION:ROLL and MSL outperformed WGL and CL across multiple endpoints. CL data revealed objective limitations that suggest caution in its use. A personalized approach considering lesion morphology, body mass index, and logistics is recommended.

Background: Pure pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ, without concurrent invasive carcinoma (IC) or ductal carcinoma in situ (DCIS), are rare and poorly understood. Their treatment is not standardized due to limited outcome data and lack of management guidelines. We aimed to gather the first large multicentric cohort of cases and analyze oncological outcomes to identify the optimal therapeutic approach. Methods: This international multicentric study (ClinicalTrials.gov ID NCT06133465) collected data from 23 centers. Patients diagnosed with pure PLCIS and/or FLCIS on core biopsy and/or final specimen pathology were included, with concurrent presence of classic (C-) LCIS permitted. Cases with associated (micro-) IC and/or DCIS were excluded. An internal slide review by a dedicated pathologist was required. A minimum follow-up of 2 years was guaranteed. Results: We collected 327 patients diagnosed with pure P-/FLCIS on core biopsy and/or on surgical specimen between 01/2004-06/2022. Of these, 58 showed P-/FLCIS only upon final histology, including 44/58 preoperative B3 lesions (17 CLCIS) and 14/58 misdiagnosed DCIS. The remaining 269 had a preoperative diagnosis of pure P-/FLCIS; of these, 82/269 cases (30.5%) upgraded on surgical specimen, with 72/82 (87.8%) to IC and 10/82 (12.2%) to DCIS (p<0.001). The upgrade rate to IC was 32.4% for PLCIS and 14.9% for FLCIS (p=0.002). Factors significantly associated with upgrade included radiological mass-like aspect, size and multicentric distribution of the lesion, irregular margins on ultrasound, and presence of necrosis on core biopsy. Our analysis focused on the 245 (74.9%) cases diagnosed as pure PLCIS (152/245, 62%) or FLCIS (93/245, 38%) on surgical specimen. Median age was 58 years, and 79.2% of the patients were diagnosed through screening mammogram. MRI was performed in 46% of cases, with 68% showing a non-mass-like enhancement. Median lesion size was 13 mm (IQR 7.5-22). Mastectomy was performed in 22 cases, while 223/245 (91%) patients underwent lumpectomy. Margin involvement (defined as P-/FLCIS on ink) occurred in 52/223 cases (23.3%), leading to 21 re-excisions, 4 mastectomies, and no further intervention in 27 cases. Factors significantly associated with positive margins included pleomorphic form, calcifications and architectural distortion on mammogram, a radiological mass-like aspect, and multicentric distribution. Sentinel lymph node biopsy was performed in 62/245 (25.3%) cases, with no positive lymph nodes found. Adjuvant radiotherapy was administered to 38/245 (15.5%) patients, while 50/245 (20.4%) received adjuvant endocrine therapy. With a median follow-up of 76 months (IQR 34-91), local recurrence (LR) occurred in 35/245 (14.3%) cases, including 16 IC, 2 DCIS and 17 P-/FLCIS. Involved margin (p<0.001) and multicentric radiological distribution (p=0.001) were associated with LR. Adjuvant therapies did not influence recurrence rates (RR) in patients with clear margins (p=0.3), nor in those with involved margins (p=0.06). Among patients with positive margins, local RR was significantly higher in patients who did not have a re-excision (22/27, 81.5%) compared to those who did (2/25, 8%) (p<0.001). RR were similar between pure PLCIS and FLCIS cases (15.1% vs. 12.9%, p=0.427). The 5-year recurrence free survival was 84.6% for the entire cohort (95%CI 78.8-89%). Conclusion: In this cohort, yet the largest collected to date, the upgrade rate of pure P-/FLCIS to IC/DCIS was 30.5%, suggesting careful preoperative assessment. Axillary surgery should be omitted. Involved margins were associated with LR (invasive in nearly half of cases) while adjuvant therapies were not. Surgery with clear margins, and not adjuvant therapies, seem to be the mainstay of treatment for this disease. Citation Format: Massimo Ferrucci, Daniele Passeri, Francesco Milardi, Rocco Cappellesso, Paola Del Bianco, Gian Luca De Salvo, Angelo Paolo Dei Tos, Gianluca Franceschini, Pietro Maria Ferrando, Lucio Fortunato, Matteo Ghilli, Adele Sgarella, Carla Cedolini, Francesca Catalano, Serena Scomersi, Simone Mele, Francesca Muscara, Graziano Meneghini, Eugenia Raffaeli, Donato Casella, Christian Rizzetto, Francesca Pellini, Guido Papaccio, Eleonora Meduri, Michela Stumpo, Simona Grossi, Leonardo Barellini, Alba Di Leone, Cristian Scatena, John Benson, Angela Santoro, Virginia Castagnetta, Isabella Castellano, Jacopo Cumbo, Ada Ala, MD; Gianmarco Piccolino, Chiara Anghelone, Serena Bertozzi, Martina Rapisarda, Margherita Fezzi, Moira Ragazzi, Filippo Cappello, Nicola Rocco, Giacomo Montagna, Walter Paul Weber, Alberto Marchet. Clinical Management and Oncological Outcomes of Pure Pleomorphic and Florid Lobular Carcinoma in Situ of the Breast: Results from the MultiLCIS Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS18-05.

Introduction Multilocus Inherited Neoplasia Allele Syndrome (MINAS) is a condition defined by the presence of germline pathogenic variants in more than one Cancer Susceptibility Gene (CSG). MINAS is still underreported in the literature and public databases. Since MINAS-related phenotypes are difficult to predict, case descriptions may contribute to risk assessment, treatment, and personalized surveillance for proband and relatives. Case Description: Here we report a unique case of early onset, bifocal, non-Triple Negative breast cancer in a 31-year-old woman. Fast metastatic dissemination involving the brain caused the death of the patient in a few months. Her multigene panel testing showed the co-occurrence of pathogenic variants in PALB2 (c.1221del; p.Thr408fs*40), ATM (c.8545C>T; p.Arg2849*), PMS2 (c.1919C>A; p.Ser640*), and MUTYH (c.1103G>A; p.Gly368Asp). The patient inherited the ATM and MUTYH variants from the mother, and PALB2 and PMS2 variants from the father. The brother inherited the maternal ATM and paternal PMS2 variants. A baseline imaging-based family screening excluded malignancies in both parents and in the brother. Tailored monitoring is ongoing based on the risk predicted by pathogenic variants identified in family members. Conclusions: Currently, there are no predictive tools available to determine organ-specific cancer risk in MINAS patients. Given the uncertainty in predicting the phenotypic effect of multiple variants in CSGs, ongoing clinical surveillance and sharing data from complex cases are crucial for improving risk stratification in this condition.

Totally implanted venous access ports (TIVAPs) have been established as effective and safe devices for oncologic patients. In breast cancer setting, the implant of the reservoir at mid-arm allows the absence of additional scars on the chest and the easier access to the port with significant cosmetic and psychological advantages. In the last decades, breast surgery has made great progresses to ameliorate the cosmetic results even in mastectomy techniques. In fact, many studies have demonstrated that negative body image perception affects physical and psychological wellbeing of survivors. Despite this evidence, limited importance is still reserved to TIVAPs placement site, which is traditionally the chest. It is not unusual to see patients after a nipple-sparing mastectomy with excellent cosmetic result who show a disfiguring scar on their upper chest due to TIVAP placement. We report the case of a young woman with BRCA2-related breast cancer who underwent bilateral nipple sparing mastectomy with immediate reconstruction and adjuvant chemotherapy. Her TIVAP was located at the mid-arm, which is still an uncommon site compared to the upper chest. An optimal cosmetic result was obtained both in breast reconstruction and in the arm site of port, with high-rate patient satisfaction. This case presentation aims to raise awareness towards women's body image preservation, particularly in the choice of TIVAP placement: in most cases neckline and upper chest should be avoided for a better patient related outcome.

Accurate evaluation of breast cancer on bioptic samples is of fundamental importance to guide therapeutic decisions, especially in the neoadjuvant or metastatic setting. We aimed to assess concordance for oestrogen receptor (ER), progesterone receptor (PR), c-erbB2/HER2 and Ki-67. We also reviewed the current literature to evaluate our results in the context of the data available at present. We included patients who underwent both biopsy and surgical resection for breast cancer at San Matteo Hospital, Pavia, Italy, between January 2014 and December 2020. ER, PR, c-erbB2, and Ki-67 immunohistochemistry concordance between biopsy and surgical specimen was evaluated. ER was further analysed to include the recently defined ER-low-positive in our analysis. We evaluated 923 patients. Concordance between biopsy and surgical specimen for ER, ER-low-positive, PR, c-erbB2 and Ki-67 was, respectively, 97.83, 47.8, 94.26, 68 and 86.13

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings.Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients.Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units.Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR.Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients.Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC.Registration: Eudract number NCT05798806.

Importance Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent. Objective To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography. Design, Setting, and Participants The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023. Intervention Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group). Main Outcomes and Measures The primary end point of the study was distant disease–free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations. Results Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor–positive ERBB2 (formerly HER2 or HER2/neu ), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group. Conclusions and Relevance In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan. Trial Registration ClinicalTrials.gov Identifier: NCT02167490

Background: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. Patients and methods: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). Results: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2-(OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. Conclusion: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Purpose Breast lesions classified as of “uncertain malignant potential” represent a heterogeneous group of abnormalities with an increased risk of associated malignancy. Clinical management of B3 lesions diagnosed on vacuum-assisted breast biopsy (VABB) is still challenging: surgical excision is no longer the only available treatment and VABB may be sufficient for therapeutic excision. The aim of the present study is to evaluate the positive predictive value (PPV) for malignancy in B3 lesions that underwent surgical excision, identifying possible upgrading predictive factors and characterizing the malignant lesions eventually diagnosed. These results are compared with a subset of patients with B3 lesions who underwent follow-up. Methods A total of 1250 VABBs were performed between January 2006 and December 2017 at our center. In total, 150 B3 cases were diagnosed and 68 of them underwent surgical excision. VABB findings were correlated with excision histology. A PPV for malignancy for each B3 subtype was derived. Results The overall PPV rate was 28%, with the highest upgrade rate for atypical ductal hyperplasia (41%), followed by classical lobular neoplasia (29%) and flat epithelial atypia (11%). Only two cases of carcinoma were detected in the follow-up cohort, both associated with atypical ductal hyperplasia at VABB. Conclusion Open surgery is recommended in case of atypical ductal hyperplasia while, for other B3 lesions, excision with VABB only may be an acceptable alternative if radio-pathological correlation is assessed, if all microcalcifications have been removed by VABB, and if the lesion lacks high-risk cytological features. Key Points • Surgical treatment is strongly recommended in case of ADH, while the upgrade rate in case of pure FEA, especially following complete microcalcification removal by VABB, may be sufficiently low to advice surveillance as a management strategy. • The use of 11-G- or 8-G-needle VABB, resulting in possible complete diagnostic excision of the lesion, can be an acceptable alternative in case of RS, considering open surgery only for selected high-risk patients. • LN management is more controversial: surgical excision may be recommended following classical LN diagnosis on breast biopsy if an additional B3 lesion is concurrently detected while in the presence of isolated LN with adequate radiological-pathological correlation follow-up alone could be an acceptable option.

Recent developments in sentinel lymph node (SLN) and radio occult lesion localization (ROLL) highlight the need for a multimodal contrast agent, providing better presurgical PET imaging and improved intraoperative mapping thanks to fluorescence detection. For this reason, we have studied a trimodal SLN/ROLL targeting agent (99mTc-68Ga-ICG) with commercially available kits of macroaggregated or nanocolloidal albumin (MA/NC-HSA). 68Ga PET imaging does provide better spatial resolution and makes it possible to predict signal intensity during surgery. The presence of 99mTc assesses the efficacy of these compounds in vitro and also during the surgery procedure. The aim of this study was to optimise the labelling and tagging of these two radiopharmaceuticals and assess their yields and stability. Kits of MA/NC-HSA particles (Pulmocis® and NanoAlbumon®) were used for sequential radiolabelling with 99mTc and 68Ga. Fluorescent tagging was performed using indocyanine green, a tricarbocyanine dye. The ITLC radiochemical purity of the trilabelled MA/NC-HSA was >95%. Fluorescent purity was measured by scanning the strips with a PhotoDynamicEye probe. Finally, in vitro stability tests, performed with DTPA and human serum solutions, assessed the efficacy of fluorescent tagging and radiolabelling.