Menekse Göker

Importance: Positive margins occur in 12% to 30% of breast-conserving surgeries and are associated with increased local recurrence risks. Accurate and efficient intraoperative margin assessment, therefore, remains an unmet clinical need. Objective: To evaluate the success rate of intraoperative specimen positron emission tomography (PET)–computed tomography (CT) imaging in addressing positive margins in patients with invasive ductal carcinoma. Design, Setting, and Participants: This was an interventional, multicenter, nonrandomized clinical trial that recruited patients from June 2022 to March 2025. Patients were followed up 2 weeks after surgery. Six European breast cancer centers participated and integrated specimen PET-CT imaging into their routine surgical flow. The analysis included eligible patients with early-stage breast cancer scheduled for breast-conserving surgery. Interventions: Patients received an intravenous injection of low-dose ¹⁸ F-fluorodeoxyglucose (FDG; 0.8 MBq/kg). After tumor excision, the specimen was imaged intraoperatively using a dedicated specimen PET-CT scanner. Surgeons interpreted PET-CT images intraoperatively, and additional tissue was excised when margins were deemed suspicious to achieve final negative margins. Main Outcomes and Measures: The primary outcome was the success rate of specimen PET-CT in addressing positive margins for the invasive component in patients undergoing breast-conserving surgery for invasive ductal carcinoma. Secondary outcomes included success rates in other breast cancer subtypes, final positive margin rates, reoperation rates, and diagnostic performance using histopathology as the reference standard. Results: The analysis cohort consisted of 148 female patients with a median (IQR) age of 65 (53-73) years and a median (IQR) preoperative tumor size of 17 (12-22) mm. For the invasive component of invasive ductal carcinoma, success rates increased from 83.3% (70 of 84 patients) without intraoperative margin assessment (IMA) to 86.9% (73 of 84 patients) with routine margin assessment and to 95.2% (80 of 84 patients) with specimen PET-CT ( P < .001 vs no IMA). Across all study groups, success rates improved from 76.4% (113 of 148 patients) without IMA to 81.8% (121 of 148 patients) with routine margin assessment techniques and to 91.9% (136 of 148 patients) with specimen PET-CT ( P < .001 vs no IMA; P = .009 vs standard-of-care IMA). Conclusions and Relevance: Study findings show that specimen PET-CT imaging was associated with an improvement in the assessment of positive margins for invasive component in patients undergoing conserving surgery for early breast cancer. The use of this integrated approach might lead to a substantial reduction of re-excision rates after breast-conserving surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04999917

Positive surgical margins in breast-conserving surgery (BCS) for breast cancer occur in 20% of cases, making intraoperative margin assessment (IMA) crucial to avoid re-operations. This study evaluated specimen PET-CT imaging for IMA in 41 patients undergoing BCS. Specimen PET-CT imaging was performed with the ß-CUBE/X-CUBE (MOLECUBES) or the AURA 10 (XEOS). Seven physicians, with varying experience, assessed margin status postoperatively as positive, close (≤1 mm), or negative using PET-CT images at 10 min acquisition time and low reconstructed [¹⁸F]FDG dose (0.8MBq/kg). Close margins on PET-CT were analyzed once as positive and once as negative. Histopathology was the gold standard. The proposed technique showed 91% sensitivity and 86% specificity for invasive ductal carcinoma (IDC). Histopathology identified 9 positive margins in 31 IDC cases; 88% were detected by all physicians on specimen PET-CT whereas standard of care identified 44%. Therefore, specimen PET-CT will improve IMA in BCS and potentially reduce re-operation rates. The trial is registered since 20/01/2020 on ClinicalTrials.gov (ID: NCT04343079) with the title: “Intra-operative PET-CT: a Novel Approach to Determine Excision Margins in Lumpectomy Breast Cancer”.

Magnetic resonance imaging (MRI) can be used for the preoperative local staging of endometrial cancer (EC). The presence of ≥pT1b disease (i.e., tumor invasion in ≥50% of the myometrium, into the cervical stroma or spread outside the uterus) has important prognostic value and implications for the decision to perform lymphadenectomy. The purpose of this study was to assess the performance of MRI for the detection of ≥pT1b disease and to evaluate whether tumor size measured via MRI was predictive for ≥pT1b disease, independent of imaging signs of deep invasion. MRI T-staging and tumor diameter and volume were correlated with histopathology of the hysterectomy specimen in 126 patients. MRI had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 70.0%, 83.3%, 79.2%, 75.3% and 77.0%, respectively, for the detection of ≥pT1b disease. A tumor diameter of ≥40 mm and volume of ≥20 mL measured via MRI were predictive for ≥pT1b disease at rates of 78.3% and 87.1%, respectively. An EC size of at least 5 mm upon MRI was predictive for ≥pT1b disease in more than 50% of cases. Our results support the use of MRI in the preoperative staging of EC and suggest including size criteria in EC staging guidelines.

Purpose: The aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC). Methods: Data of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001–2015, were analyzed. Results: ILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan–Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08–2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78–0.91), LVSI (hazard ratio 1.75, 95% CI 1.12–2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03–5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02–1.07), LVSI (hazard ratio 3.62, 95% CI 1.92–6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73–0.89). Conclusion: The histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area using the following cut-offs: 0%; <5%; 5–9%; and 10–50%. The PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections using SP142 and 22C3 antibodies. Results: A total of 82% of the sixty-six patients were hormone receptor positive and 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs (≥1%) were present in 64% of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of ≥1%, and using the 22C3 antibody, 28% had a positive PD-L1 score of ≥1. There was no correlation between sTILs or PD-L1 expression and tumor size, tumor grade, nodal status, expression of estrogen receptor (ER), or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression; however, this was not associated with a survival improvement. Additional large trials are needed to understand immune infiltration in lobular cancer, especially in the pleomorphic subtype.

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs, and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area, using the following cut-offs: 0%; <5%; 5-9%; and 10-50%. PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections, using the SP142 and 22C3 antibodies. Results: 82% of the sixty-six patients were hormone receptor-positive; 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs were present in 64% (1%) of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of 1%, and 28% had a positive PD-L1 score of 1 using the 22C3 antibody. There was no correlation of sTILs or PD-L1 expression with tumor size, tumor grade, nodal status, expression of estrogen receptor (ER) or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression, however this was not associated with survival benefit. Additional large trials are needed to understand the immune infiltration in lobular cancer, even more in the pleomorphic subtype.

Amyloidosis is an uncommon disorder characterized by extracellular accumulation of misfolded proteins in tissues. We report a unique case of localized breast amyloidosis in an asymptomatic 56-year-old woman with systemic lupus erythematosus, presented as suspicious microcalcifications without mass on mammography. Vacuum biopsy confirmed amyloidosis, producing the typical apple-green birefringence under polarized light after staining with Congo-red. Further workup and follow-up to exclude development into systemic amyloidosis or hematologic malignancy is recommended. If negative, the prognosis is very good, thus no further treatment is needed. A brief review of the literature revealed more about the typical findings and recommended management.

Background: One of the current challenges in breast cancer is the appropriate treatment of invasive lobular breast cancer (ILC) and defining the high-risk group within ILC. The biological character of ILC typically translates to a good prognosis, however several studies have indicated that the long-term prognosis is worse than for patients diagnosed with the more commonly invasive ductal carcinoma (IDC). Many genomic tests are now available to determine whether those patients are at high-risk (HR) and enable tailored treatment. Unfortunately, most of the studies in which these genomic tests have been evaluated entail retrospective analysis of a prospective trial. Aim: This review focuses on the validation of the available genomic assays based on trials performed in ILC patients, where in some instances the various subtypes of ILC (classical, pleomorphic, non-classic type) were taken into account. Results: Using Oncotype DX in retrospective studies, only 1.3% to 8% of ILC tumors were categorized as HR tumors. For MammaPrint, 24% of patients were classified as HR, which was associated with poor outcome. In a recent sub-analysis of the Mindact study comprising 487 ILC patients, 16.2% were high genomic risk. Endopredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, and the Breast Cancer Index have been validated in patients receiving only endocrine treatment. Conclusion: Although ILC accounts for the second most common breast cancer subtype in women, none of these tests encompass tumor morphology in their algorithms. Prospective studies on ILC with genomic assays are warranted given the various subtypes of and treatment options for this underestimated, but frequently occurring cancer. Relevance for patients: Genomic assays can be employed in ILC patients to predict the risk of recurrence and identify those patients who might benefit from chemotherapy in addition to their standard treatment regimen.

Purpose The aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC). Methods Data of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001–2015, were analyzed. Results ILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan-Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08–2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78–0.91), LVSI (hazard ratio 1.75, 95% CI 1.12–2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03–5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02–1.07), LVSI (hazard ratio 3.62, 95% CI 1.92–6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73–0.89). Conclusion The histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.