Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer

Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC). Recent results of central pathology review of two large randomized clinical trials have demonstrated relative overdiagnosis of ILC, as only similar to 60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons of this discrepancy, we undertook a worldwide survey on the current practice of diagnosing BC as ILC. A survey was drafted by a panel of pathologists and researchers from the European lobular breast cancer consortium (ELBCC) using the online tool SurveyMonkey (R). Various parameters such as indications for IHC staining, IHC clones, and IHC staining procedures were questioned. Finally, systematic reporting of non-classical ILC variants were also interrogated. This survey was sent out to pathologists worldwide and circulated from December 14, 2020 until July, 1 2021. The results demonstrate that approximately half of the institutions use E-cadherin expression loss by IHC as an ancillary test to diagnose ILC and that there is a great variability in immunostaining protocols. This might cause different staining results and discordant interpretations. As ILC-specific therapeutic and diagnostic avenues are currently explored in the context of clinical trials, it is of importance to improve standardization of histopathologic diagnosis of ILC diagnosis

Deep learning analysis of contrast-enhanced spectral mammography to determine histoprognostic factors of malignant breast tumours

To evaluate if a deep learning model can be used to characterise breast cancers on contrast-enhanced spectral mammography (CESM)

Clinical relevance of circulating ESR1 mutations during endocrine therapy for advanced hormone-dependent endometrial carcinoma

Abstract Objective Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and can be monitored using circulating tumor DNA (ctDNA). The aim of this study was to explore the incidence and clinical relevance of circulating ESR1 mutations in patients treated by AI or megestrol acetate (M) for advanced endometrial carcinoma. Methodology This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR + endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AI or M. Analyses were performed before exposure and at progression/during endocrine therapy. Results Twenty-two patients were included: 13 were treated with AI, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed. 68.1% of the patients had low-grade endometrial carcinoma and 54.5% had received chemotherapy in the metastatic setting. The median duration of treatment was 152 days (min 47 – max 629) with AI and 155 days (min 91-max 1297) with M. Under AI, there was no ESR1 mutation at baseline, and one Y537C mutation at progression with a variant allele frequency (VAF) of 0.14%. Under M, one patient had a Y537C (VAF 0.2%) at baseline that disappeared during treatment. Another patient had a Y537S mutation emergence at progression after 91 days of treatment (VAF 1.83%). There was no significant difference between the circulating DNA concentration before and after hormone therapy (p = 0.16). Conclusion ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated

CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma

International audienceThe CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter. Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing. In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p ¼ 0.012 and p 40%) of the CXCL12 promoter was observed in only a few tumoural samples (5/23) and was associated with a lower expression of the gene (p ¼ 0.03). Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases

Delineation of small mobile tumours with FDG-PET/CT in comparison to pathology in breast cancer patients.

International audienceVarious segmentation methods for 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images were correlated with pathological volume in breast cancer patients as a model of small mobile tumours. Thirty women with T2-T3/M0 breast invasive ductal carcinoma (IDC) were included prospectively. A FDG-PET/CT was acquired 4 ± 3d before surgery in prone and supine positions, with/without respiratory gating. The segmentation methods were as follows: manual (Vm), relative (Vt%) and adaptive (Va) standard uptake value (SUV) threshold and semi-automatic on CT (Vct). Pathological volumes (Vpath) were measured for 26 lesions. The mean (±SD) Vpath was 4.1 ± 2.9 mL, and the lesion displacements were 3.9 ± 2.8 mm (median value: 3 mm). The delineated VOIs did not vary with the acquisition position nor with respiration, regardless of the segmentation method. The Vm, Va, Vct and Vt% methods, except Vt30%, were correlated with Vpath (0.5<r<0.8). The Vt50% and Vm were the most accurate methods (mean±SD: 0.0 ± 1.6 mL and +0.6 ± 1.8 mL, respectively), followed by the Vct method. When compared with pathology, small lesions (diameter <50mm) with limited respiratory displacement (i.e., breast or apical lung lesions) are best delineated on FDG-PET/CT using a 50% SUVmax threshold. The acquisition position and respiratory gating did not modify the delineated volumes

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

International audienceAbstract Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment

The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma

International audienceObjectives: To assess the prognostic value of the expression profile of the main genes implicated in hypoxia, glucose and lactate metabolism, inflammation, angiogenesis and extracellular matrix interactions for the metastatic spread of head and neck squamous cell carcinoma.Patients and methods: Using a high-throughput qRT-PCR, we performed an unsupervised clustering analysis based on the expression of 42 genes for 61 patients. Usual prognostic factors and clustering analysis results were related to metastasis free survival.Results: With a median follow-up of 48 months, 19 patients died from a metastatic evolution of their head and neck squamous cell carcinoma and one from a local recurrence. The unsupervised clustering analysis distinguished two groups of genes that were related to metastatic evolution. A capsular rupture (p = 0.005) and the ''cluster CXCL12 low'' (p = 0.002) were found to be independent prognostic factors for metastasis free survival. Using a Linear Predictive Score methodology, we established a 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) that was capable of classifying the samples into the 2 clusters with 90% accuracy.Conclusion: In this cohort, our clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. It allowed us to define a 9-gene model which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma. If confirmed by an independent prospective study, this approach may help future clinical management of these aggressive tumors

Recommandations du GEFPICS pour la prise en charge des prélèvements dans le cadre du traitement néoadjuvant du cancer du sein

International audienceNeoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems)

[2021 update of the GEFPICS’ recommendations for HER2 status assessment in invasive breast cancer in France]

International audienceThe last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.Les dernières recommandations internationales pour l’évaluation du statut HER2 dans les cancers du sein, basées sur vingt ans d’expérience et sur les résultats de nombreuses études cliniques, ont vu le jour en 2018. D’autre part, la notion émergente de catégorie HER2 faible pour les cancers du sein de score 1+ en immunohistochimie ou de score 2+ sans amplification du gène HER2 en hybridation in situ invite à adapter les pratiques des pathologistes français. Ces modifications importantes et les bouleversements à venir sont l’occasion, pour le GEFPICS, de proposer une mise à jour des recommandations françaises pour l’évaluation du statut HER2 dans les cancers du sein. À l’ère de la médecine personnalisée, la détermination du statut HER2 reste un élément phare dans le panel des biomarqueurs théranostiques des cancers du sein, et sa bonne évaluation est garante d’une prise en charge optimale des patientes atteintes de cancer du sein. L’implication des pathologistes français dans la qualité des tests théranostiques témoigne de leur rôle essentiel dans la prise en charge des patients en cancérologie