Rationale: Positive surgical margins for invasive breast cancer (BC) treated with breast-conserving surgery (BCS) are defined as ink on tumor. The rate of positive margins is approximately 20%, since a time- and cost-effective method for margin assessment is lacking. In this study, we investigated margin status by intra-operative imaging using high-resolution ¹⁸ F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) and X-ray computed tomography (CT). Methods: Twenty patients were enrolled and received 4 MBq/kg of FDG prior to surgery. Intra-operative imaging of the specimens was performed by the MOLECUBES β-CUBE (PET) and X-CUBE (CT). Margin status was assessed by three surgeons and compared with an algorithm. The sensitivity and specificity were calculated by using histopathological assessment as a gold standard. Results: A region with high FDG uptake was visualized in all specimens. Automated analysis showed a sensitivity of 90%, a specificity of 60%, and an area under the curve (AUC) of 0.86 after ROC analysis. Margin assessment by the surgeons resulted in a mean sensitivity and specificity of 79% and 72%, respectively. Conclusions: This proof-of-concept study demonstrates that high-resolution FDG-PET/CT can facilitate intra-operative margin assessment during BCS. This technique achieves good sensitivity and specificity and may therefore reduce re-operation rates in the future.

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.

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: 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.