Genomic assays for lobular breast carcinoma

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. 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, and non-classic type) were taken into account. RESULTS: Using Oncotype DX in retrospective studies, only 1.3%–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

Method for direct correlation of high-resolution 18F-FDG-PET/CT images with histopathology in resected breast cancer specimens

Aim/Introduction: While PET/CT imaging has become widely adopted in oncology, the distribution mechanism of one of the most common radiotracers, 18F-FDG, is not yet fully understood. To study the 18F-FDG-distribution in diferent tissue types, accurate correlation of PET/CT images with the gold standard of histopathology is required. However, correlating in vivo PET/CT images with histopathology is challenging, particularly for soft breast tissue that is extremely prone to deformation during histopathological processing. To overcome this problem, we developed a strategy to correlate ex vivo high-resolution 18F-FDG-PET/CT images of resected breast cancer specimens with histopathology with unprecedented accuracy. Materials and Methods: We used a compact PET/CT scanner with a spatial resolution of 800µm and 400µm, respectively, to acquire high-resolution PET/CT images of two breast cancer specimens obtained after breast-conserving surgery of patients who received a preoperative injection with 4MBq/kg 18F-FDG. These specimens included one invasive lobular carcinoma and one invasive ductal carcinoma, treated with neoadjuvant chemotherapy. First, a pathologist sliced the specimens into ±2mm-thick lamellas, which were enclosed in tissue cassettes. Next, high-resolution PET/CT images of the cassettes containing the lamellas were acquired. Afterwards, the tissue was processed according to the local standard protocol: (1) the lamellas were fxated and embedded in parafin while still inside the cassettes; (2) a ±5µm-thin section was obtainedfrom every lamella and (3) was H&E-stained. Finally, the pathology slides were digitized using a section scanner, and these images were digitally correlated with the PET/CT images of the lamellas. Results: PET/CT images of the fresh breast lamellas were successful in all cases. The efects of tissue deformation were minimized by using the framework of tissue cassettes. A clear correlation between the high-resolution PET/CT images and histopathology was immediately visible, allowing us to study the 18F-FDG-distribution in breast tissue at a sub-millimetric scale. In both cases, a higher 18F-FDG-uptake was detected in tumorous glandular tissue compared to healthy glandular tissue. Conclusion: We developed a novel method to correlate high-resolution 18F-FDG-PET/CT images with histopathology in resected breast cancer specimens with increased accuracy. The proposed method could provide a better understanding of 18F-FDG-distribution in healthy and tumorous breast tissue on a previously uncharted scale. To our knowledge, this is the frst time high-resolution PET/CT images of breast tissue are directly correlated with its corresponding histopathology. To further improve this correlation, mathematical co-registration algorithms will be developed to optimize the alignment between the high-resolution PET/CT images and histopathology images

Tumor-infiltrating lymphocytes and PD-L1 expression in pleomorphic lobular breast carcinoma

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

Safety of pre- or postoperative accelerated radiotherapy in 5 fractions : a randomized pilot trial

Objective: Neo-adjuvant radiotherapy (NART) for breast cancer has shown promising survival results in retrospective trials. However, there are some obstacles such as a chemotherapy delay, an increased overall treatment time (OTT) and the risk of increasing surgical morbidity. Accelerated radiotherapy (RT) in 5 fractions allows to deliver NART in a very short time span and minimizes the delay of surgery and chemotherapy. This trial investigates this NART schedule for safety, feasibility and OTT. Material and methods: Twenty patients eligible for neo-adjuvant chemotherapy (NACT) and breast conserving surgery, were randomized between NART before NAG or NAG and postoperative RT. In both arms, RT treatment was given in 5 fractions to the whole breast with a simultaneously integrated boost (SIB) on the tumor(bed). Lymph node irradiation was given concomitantly in case of lymph node involvement. OTT was defined as the time from diagnosis to last surgery in the intervention group, while in the control group the time between diagnosis and last RT-fraction was used. In the intervention group NACT-delay was defined as time between diagnosis and start of chemotherapy. Results: 20 patients were included, and 19 patients completed treatment. OTT was significantly shorter in the intervention group (mean 218 days, range 196-253) compared to the control group (mean 237, range 211-268, p = 0.001). The difference in mean duration from diagnosis to the first treatment was a non-significant 4 days longer (31 vs 27 days, p = 0.28), but the start of NAG after diagnosis was delayed by 21 days (48 vs 27 days, p < 0.001). NART did not result in additional surgery complications. Conclusion: This pilot trial is the first to report on accelerated NART in 5 fractions with SIB. NART before NACT resulted in a shorter OTT with good safety results. (C) 2022 The Authors. Published by Elsevier Ltd