Abstract Background: Identifying which luminal breast cancer (BC) patients will benefit from (neo)adjuvant chemotherapy still remains a challenge. Efficient predictive tests and genomic signatures are still lacking. Because neoadjuvant chemotherapy (NACT) constitutes an in vivo chemotherapy-sensitivity test, we used the pre-treatment core biopsies to identify predictive factors of pathological response in luminal HR+/Her2- BC. Analyses on sTILS and TIL subtypes (CD3, CD4, CD8, CD20) are rare in luminal BC while a predictive value has been reported in TNBC and Her-2 positive BC. Patients and Methods: We performed a retrospective analysis of 211 patients treated with NACT followed by surgery for a T0-T4 luminal (HR+/Her-2-) breast cancer. Association of anthracyclin and taxane was used in 99% of cases. Median age was 48.4 yo (28 – 76). Initial clinical stage was: I: 0.5%, II: 67%; III: 33%. Biopsy analyses were the followings: NST carcinomas: 90%; luminal B: 82%; E&E grade I/II/III: 10%/57%/32%; KI-67 > 20%: 74%. After NACT, RCB 0-1 was observed in 32 cases (15.2%) and pCR in 19 (9.0 %) cases. All pre-therapeutic biopsies were reviewed for pathological factors, blinded to the patients’ outcomes. Clinico-pathological analyses were performed using standard methods. sTILs were estimated on H&E slides. Intratumoral CD3, CD4, CD8 and CD20 infiltrates were carried out by an independent laboratory using a machine learning model for automated and quantitative evaluation based on digital IHC stains. Correlation between sTILs and TIL subtypes were assessed by Spearman’s coefficient. Predictive factors of RCB 0/1 were explored using unconditional logistic regression analysis. After selection on univariate analysis (p< 0.05), multivariate prognostic models were developed using stepwise backward variable elimination process and compared using area under the curve (AUC). Results: sTILs levels ≥ 10% were observed in 15.2% of biopsies. 42 % of tumors had ≥ 10 % CD3-positive cells, 46% for CD4, 38% for CD8, and 8% for CD20. A high level of correlation was observed between these different markers (Spearman’s coefficient ≥ 0.73 for each comparison). By univariate analysis, significant factors (p< 0.05) associated with RCB 0-1 were: age, mitotic index (1 vs 2 vs 3), aneuploidy (1-2 vs 3), differentiation (1-2 vs 3), E&E grade (1-2 vs 3), mitotic count, Ki-67, Magee equation 3, phenotypic group (luminal A vs B), ER, sTILs and each TIL subtype. Age, E&E grade, Ki-67, Magee equation 3, sTILs and all TIL subtypes were selected for multivariate analysis. As TIL subtypes were highly correlated, different predictive models could be performed. The model we selected (called LyKi1) was constructed based on CD8 [OR 2.24 (95%CI 1.55-3.25; p< 10-4)], E&E grade [OR 3.00 (95%CI 1.22-7.42; p=0.017)] and Ki-67 [OR 1.74 (95%CI 1.09-2.76; p=0.019)]. It was highly significantly associated with RCB 0-1, with an AUC value of 0.856 (95%CI 0.756-0.916). For instance, LyKi1 could isolate a group of 30% of patients that achieved RCB 0-1 in 39.7% of cases vs 4.7% for the 70% of patients with lowest LyKi1 scores. pCR rates were 25% and 2%, respectively. Importantly, prediction value of LyKi1 remained very high if restricted to luminal B tumors (AUC 0.817; 95% CI: 0.741-0.894). Ability to predict pCR was also very high (AUC 0.837 (95%CI: 0.750-0.924) in this phenotype). Conclusion: This retrospective analysis clearly highlights the important predictive role of sTILs and TIL subpopulations for the response to an anthracyclin-taxane based regimen in a neoadjuvant setting for luminal breast cancer. Within this cohort, LyKi1 score (combining CD8, grade and Ki-67) has a very high value to predict pathological response to NACT in luminal breast cancer. Importantly, such score has to be validated in a multicentric prospective cohort and investigated in adjuvant setting. Citation Format: Marc Debled, Hugo Deboissy, Coralie Cantarel, Chloé Delfour, Léonie Alran, Marion Fournier, Nathalie Quenel-Tueux, Valérie Velasco, Foucault Chammings, Véronique Brouste, Monica Arnedos, Gaétan MacGrogan. LyKi1: a highly predictive immune-based score of pathological response to chemotherapy in luminal breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-02.

BACKGROUND:The impact of local management of pulmonary metastases on the disease course of patients with metastatic colorectal cancer is poorly assessed. METHODS:REPULCO database was a retrospective cohort on 18 years that included all patients treated for lung metastases from colorectal cancer who received local and/or systemic treatments. AIMS:Primary objective was overall survival, secondary were progression-free survival and survival without chemotherapy. RESULTS:Three hundred and fifteen patients were analyzed, 157 with only systemic treatments, 78 with only local treatments, and 80 with local and systemic treatments. Overall survival at 5 years was 26.9% (IC95%: [17.7-36.9]) for systemic treatments only, 61.0% (IC95%: [40.8-76.1]) for local treatments only, and 77.8% (IC95%: [60.1-88.3]) for local and systemic treatments. Progression-free survival at 2 years was 4.8% (IC95%: [2.1-9.2]) for systemic treatment only, 28.3% (IC95%: [17.7-39.9]) for local treatments only, and 21.8% (IC95%: [13.1-31.9]) for local and systemic treatments. Median survival without chemotherapy was 2.99 months (IC95%: [2.33-3.68]) for systemic treatments, 33.97 months (IC95%: [19.06-NA]) for local treatments, and 12.85 months (IC95%: [8.18-21.06]) for local and systemic treatments. CONCLUSION:Local treatments of lung metastasis led to prolonged survival and allowed long periods of time without chemotherapy in this cohort.

AIMS:Idylla epidermal growth factor receptor (EGFR) is a fast and fully automated mutation assay that is easy to implement. However, under the Biocartis-recommended technical conditions, tissue sections are directly introduced into the cartridge, at the risk of exhausting the tumour sample. In this study, we evaluate the performance of Idylla EGFR on extracted DNA and discuss its place within the global non-small-cell lung cancer (NSCLC) screening strategy.METHODS:577 comparative tests between Idylla EGFR on extracted DNA and next-generation sequencing (NGS) were performed across two centres.RESULTS:Preanalytical thresholds were established (20% tumour cell content, 50 ng DNA input) and challenged prospectively in routine practice. 16.8% of samples referred for screening were considered non eligible for Idylla EGFR testing. Due to discordant by design cases, Idylla EGFR sensitivity was 86.9% for currently actionable EGFR mutations. Idylla EGFR specificity was 100% in first-line screening. NGS was always feasible on the same DNA.CONCLUSION:Idylla EGFR on extracted DNA is feasible and enables tumour material to be saved compared with tissue section use. It is not necessary to replace the analytical thresholds of the Biocartis algorithm. Due to both the limits of the mutational repertoire and the high increase of targetable genes in NSCLC, the use of Idylla EGFR should be restricted to clinical emergency situations accompanied by NGS.

Aims Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions. Methods and results Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P P = 0.0005; P < 0.0001). Conclusions After ascertaining that core needle biopsy is effectively intralesional, breast hamartomas can be diagnosed with confidence by taking into account the presence of stromal changes, PASH, interlobular distribution of CD34-positive fibroblasts, HMGA2 and hormonal receptor stromal expression.

Introduction: Neoadjuvant chemotherapy (NAC) is proposed for locally advanced breast cancer (LABC) to increase the breast conservative treatment (BCT). In France, mastectomy is the risk-reducing prophylactic surgical strategy only for pre-symptomatic germline BRCA-mutated (gBRCAm) patients. On the other hand, BCT is proposed to all patients following NAC based on clinical response, even for patients do not demonstrating germline BRCA mutation. Moreover, in the case of BRCA mutation, local recurrence risk is higher in the BCT group (23%) vs mastectomy (5%). The aim of this retrospective one-institution analysis is to evaluate if the knowledge of gBRCAm status impact shared surgical decision between surgeons and patients. Patients and methods: Inclusion criteria were: (i) patients treated for unilateral LABC, T2-4, N≥0, M0 by NAC, and (ii) patients who underwent germline BRCA screening. BRCA screening, using targeted next-generation screening, was carried out either during NAC (rapid process) or after surgery. Deleterious mutations were confirmed using Sanger sequencing before passing on the results to the clinical geneticist. Some gBRCAm patients from Olympia clinical trial study were also included. Patients were followed-up over a long term for overall survival (OS), local recurrence (LR) and disease-free recurrence interval (DRFI). Chi-square, Fischer test and T-test and Wilcoxon test were used to generate statistical descriptive analysis. Results: Between 2007 and 2015, 988 women were treated for LABC at our institution. Among them, 151 patients underwent clinical genetic testing for gBRCAm based on these criteria: young age at diagnosis or familial history of breast or ovarian cancer or histological characteristics as grade 2/3, Her2-3+ or basal like. A total of 125 patients were included in the study; 27 patients had germline mutations (MT group) and no mutations were detected in 98 patients (WT). Significant differences between the two groups (MT vs WT) were observed for - Intrinsic tumor subtypes basal like (64.3% vs 42.5%, p=0.0432) - ER are more often negative (21.4% vs 46.8%, p=0.0165). Among the 29 patients who underwent germline screening during NAC and eligible for BCT, all the patients with gBRCAm choose mastectomy (100%). Among the 96 patients with screening mutation after breast cancer treatment, 6 of the 19 patients with gBRCAm had a mastectomy (28%). In the 25 gBRCAm patients, 15 had a BCT and 11 a mastectomy. In the 98 wtBRCA patients, 70 had a BCT and 28 a mastectomy. After a follow-up of 76.8 months of 83 patients with BCT, we observed 9 LR, 7% in the WT group and 30.8% in the MT group. The median delay of disease recurrence is 40.8 months [22-113]. According DRFI and OS, there is not statistically difference between the WT and the MT group, at 3 years and 5 years of follow up. Discussion: In this selected subgroup of patients, gBRCAm rate is higher (21%) than the rate based on familial criteria for BRCA testing (12%). Regarding the rationale for BCT or mastectomy procedure in LABC and pre-symptomatic gBRCAm patients, this study led us to establish mastectomy as the sole risk-reducing strategy surgery procedure for gBRCAm patients. Moreover, 100% gBRCAm patients chose mastectomy; the mastectomy rate was lower when the patient was unaware of their BRCA status (26%). The LR rate was higher in the gBRCAm vs wtBRCA with a statistical difference. In LABC patients with high genetic risk, the knowledge of mutation status could influence patients’ and surgeons’ choice of surgery. In case of gBRCAm status, mastectomy is recommended to decrease LR risk Citation Format: Nicolas Sevenet, Christine Tunon de Lara, Jeanne Leroux, Françoise Bonnet, Marc Debled, Delfine Lafon, Emmanuelle Barouk-Simonet, Marion Fournier, Adeline Petit, Virginie Bubien, Nathalie Quenel-Tueux, Véronique Brouste, Gaëtan MacGrogan. Germline BRCA screening for locally advanced breast cancer treated by neoadjuvant chemotherapy: Defining a subgroup with high rate of mutation and local relapses [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-10.

The similarities between sporadic basal-like breast cancer (BLBC) and BRCA1-mutated breast tumours raise the possibility that deregulation of the same pathway may underlie these tumour types. The aim of this study was to determine if PTEN aberrations are characteristic of both BRCA1 tumours and sporadic TN breast carcinomas with low BRCA1 expression, and can thus be used to identify sporadic tumours potentially sensitive to PARP inhibitors. Twelve BRCA1 tumours, 19 non-BRCA familial breast tumours and 71 unselected TN breast carcinomas were screened for PTEN mutations and assessed for PTEN expression and BRCA1 mRNA expression. Loss of PTEN expression was observed in 67% of BRCA1 tumours and more specifically in 89% of TN BRCA1 tumours highlighting the link between PTEN loss and BLBC in the context of germline BRCA1 mutations. Regarding unselected TN tumours, 56% showed PTEN expression loss and 35% displayed low BRCA1 mRNA expression. Unlike familial breast cancers with low BRCA1 mRNA expression, no significant correlation was observed between the loss of PTEN expression and low BRCA1 mRNA expression in this unselected TN tumours panel. Our data suggest that, unlike the germinal context, PTEN and BRCA1 alterations in sporadic TN breast tumours are independent events.

BACKGROUND. A recently introduced digital breast tomosynthesis (DBT) device allows acquisition of DBT spot compression views with a small paddle during DBT acquisition. OBJECTIVE. The purpose of this study was to evaluate the impact on diagnostic performance of obtaining a DBT spot compression view for assessment of equivocal DBT findings. METHODS. This retrospective study included 102 women (mean age, 60 years) in whom a DBT spot compression view was obtained to characterize an equivocal finding on DBT at the performing radiologist's discretion. The DBT examinations were performed from December 14, 2018, to December 18, 2019. Two fellowship-trained breast radiologists and one breast imaging fellow, who were aware of the location of the equivocal lesions, independently reviewed the examinations. Readers first assigned a BI-RADS category using standard DBT views and then immediately assigned a category using the DBT spot compression view. BI-RADS categories 2 and 3 were considered negative, and categories 4A and greater were considered positive. Histology and at least 1 year of imaging follow-up served as the reference standard. Intrareader agreement for one reader and interreader agreement among all readers were evaluated with kappa coefficients. Diagnostic performance was compared between DBT with and DBT without spot compression views by use of McNemar tests. RESULTS. Intrareader agreement increased from 0.43 to 0.72, and interreader agreement increased from 0.21 to 0.45 on the basis of kappa coefficients for DBT without and with spot compression views. Eighteen cancers were present. Compared with standard DBT views, DBT spot compression views yielded significantly increased accuracy for all three readers (75% vs 90%, 74% vs 94%, 72% vs 94%); significantly increased specificity for all three readers (69% vs 90%, 75% vs 94%, 68% vs 93%); and significantly increased sensitivity for one reader (67% vs 94%) without significant change in sensitivity for the two other readers (89% vs 100%, 100% vs 89%). Radiation dose was 1.97 mGy for the DBT spot compression view versus 1.78-1.81 mGy for standard DBT craniocaudal and mediolateral oblique views. CONCLUSION. Use of the DBT spot compression view increased intrareader agreement, interreader agreement, and diagnostic accuracy (primarily owing to improved specificity); the supplemental dose for the spot compression view was slightly higher than that for a standard DBT view. CLINICAL IMPACT. DBT spot compression may help characterize equivocal DBT findings, reducing further workup for benign findings.

INTRODUCTION:Guidelines do not recommend FDG-PET CT for the staging of MIBC as a standard. The objectives of the study are to assess the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification according to FDG-PET CT results in MIBC.PATIENTS AND METHODS:From January 2005 to December 2017, we carried out a retrospective analysis of patients with MIBC who had a FDG-PET CT for staging in two expert centres in Bordeaux, France, and analyzed its clinical value in this setting. Nodal and metastatic staging on CT scan (CT) and FDG-PET CT were done independently.RESULTS:Accuracy of LN staging from CT and FDG-PET CT at initial diagnosis was analyzed in 85 patients (including 70 patients treated with neoadjuvant chemotherapy (NAC)) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (80.8% versus 26.9%) but the specificity was low (54.2% vs. 83.1%). The Youden index was better for FDG-PET CT (0.35; 0.1 for CT) and FDG-PET CT appeared to be more accurate for determining LN staging of MIBC. FDG-PET CT findings enabled a treatment decision modification in 34/130 patients (26.1%): a therapeutic intensification (9.2%), including surgery not previously planned and/or modified fields of radiotherapy; or a de-escalation (16.9%), mostly avoiding surgery.CONCLUSION:FDG-PET CT was more sensitive for detection of LN involvement at initial diagnosis of MIBC than CT alone. In our study, treatment decisions were modified, according to FDG-PET CT results, in almost a quarter of patients.

Background: When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse. Materials and methods: We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors. Results: Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC). Conclusions: Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis.

Introduction > Women identified as high-risk for breast cancer may choose between close followup and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers. Methods > All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts. Results > 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%). Discussion > Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.

Background Colon cancer is one of the most common leading causes of death worldwide. Prognostic at an early stage is an efficient way to decrease mortality. The Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a Protein Disulfide Isomerase (PDI) is highly expressed in various tumours and is involved in tumour-associated processes. This study aims at examining the expression of AGR2 protein in colon cancer. Methods AGR2 protein expression was determined using immunohistochemistry on tissue samples issued from a cohort of 82 colorectal carcinomas. Results AGR2 protein expression was significantly higher in tumours than in adjacent nontumour controls. AGR2 expression subgroup analyses indicated that AGR2 low expression in colon cancer patients was significantly associated with worse overall survival. Mucinous colon cancers exhibited higher AGR2 expression levels than non-mucinous cancers. Additionally, tumours with microsatellite instability (MSI) were characterised by a strong upregulation of AGR2 mRNA and protein expression despite an absence of MLH1/MSH2 mutations. Conclusions Our findings indicate that high AGR2 protein expression is correlated with longer patient survival and that AGR2 overexpression is associated with MSI tumours and could represent an MSI biomarker. Overall, AGR2 might serve as a biomarker to stratify colon tumours and to contribute to the prognosis of colon cancer patients.

Neurotensin receptor-1 (NTS1) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified. We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS1 expression and clinical, pathological, and biological parameters, as well as patient outcomes. Out of 1419 primary breast tumors, moderate to strong positivity for NTS1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main “correlates” of a nuclear location of NTS1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS1-positive samples, cytoplasmic expression of NTS1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS1 nuclear staining. Ancillary analysis showed NTS1 expression in 73% of invaded lymph nodes from NTS1-positive primaries. NTS1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS1-targeting strategy, including radiopharmaceuticals for imaging and therapy.

Chez les femmes considérées à haut risque de cancer du sein, la mastectomie est une alternative à la surveillance rapprochée. La chirurgie mammaire de réduction du risque (CMRR) présente des bénéfices et des risques, dont l’évaluation est particulièrement importante car sa réalisation dépend du choix de la patiente. L’objectif de cette étude était d’étudier les pratiques de la CMRR dans un centre français de lutte contre le cancer et notamment d’évaluer la morbidité et le risque de découverte fortuite de cancer. Il s’agit d’une étude rétrospective, descriptive s’étendant de 2007 à 2017. Les dossiers de toutes les patientes ayant bénéficié d’une CMRR bilatérale ou controlatérale ont été analysés. Soixante-dix-neuf patientes ont été opérées sur la période d’étude dont 58,2 % d’une mastectomie controlatérale. Le critère de recevabilité de la demande de mastectomie était l’existence d’une mutation génétique dans 86,1 % des cas. Une complication postopératoire est survenue chez 43,0 % des patientes et une réintervention a été nécessaire dans 72,1 % des cas. À l’analyse anatomopathologique, un cancer a été découvert dans 11,4 % des cas ; il s’agissait dans deux cas (2,5 %) d’un carcinome infiltrant de type triple négatif. La CMRR reste à ce jour la mesure la plus efficace de prévention du cancer du sein en France. Chaque femme doit, avant d’y recourir, être clairement informée de la balance bénéfice–risque, en particulier de la forte probabilité de présenter une complication, de la nécessité de plusieurs temps opératoires et de l’existence d’un risque de découvrir un cancer à l’analyse anatomopathologique. L’accompagnement préopératoire doit être optimisé afin de guider au mieux ces femmes dans leur processus décisionnel. Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers. All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts. 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%). Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.

ObjectiveTo describe BI-RADS features and evaluate conspicuity of breast cancer on digital breast tomosynthesis (DBT) according to their molecular profile.Materials and method Institutional review board was obtained for this retrospective study. Consecutive patients with histologically proven breast cancers who underwent digital breast tomosynthesis (DBT) with 2D synthetic mammography (SM) and digital mammography (DM) at the time of diagnosis were included. Morphological features and conspicuity of cancers on DM, SM and DBT were evaluated in consensus by two breast radiologists. Imaging features were compared across molecular subtypes (luminal, triple negative (TN) and HER2+) using Fisher’s exact test and between DBT and SM and DM using McNemar’s test. Conspicuity was compared between DBT and SM and DM using Wilcoxon matched pairs test and between each molecular subtype using the Wilcoxon test.ResultsOne hundred and eleven consecutive patients were included. On DBT, TN cancers more frequently presented as masses with microlobulated margins (P = 0.04) while HER2 + cancers were more often associated with microcalcifications (P = 0.02). Greater conspicuity on DBT in comparison to DM was observed for cancers with low Ki67 (P = .015), less aggressive tumours (P = .005), positive ER (P = 0.005), positive PR (P = .005) or negative HER2 (P = .024), and for luminal molecular profiles (P = 0.012) while no difference was observed between the two techniques for TN (P = .73) and HER+ (P = .79) tumours.ConclusionDBT reveals specific features of breast cancers according to their molecular characteristics. In comparison with DM, DBT improves conspicuity of luminal subtype cancers and tumours demonstrating less aggressive features on pathology.

OBJECTIVES:To evaluate the diagnostic accuracy of breast MRI in identifying lesions requiring excision for patients with suspicious nipple discharge but normal mammograms and ultrasounds.METHODS:Between September 2013 and May 2019, 106 female participants (mean age 57.9 years) were consecutively included in this prospective multicenter study; 102 were retained for analysis. MRI was considered negative in the absence of suspicious enhancement and positive in cases of ipsilateral abnormal enhancement (BI-RADS 3 to 5). Final diagnoses were based on histological findings of surgical or percutaneous biopsies or at 1-year follow-up. We considered all lesions requiring excision found on pathology (papilloma, atypia, nipple adenomatosis, or cancer) as positive results. We considered spontaneous resolution of the discharge at 1 year as a negative result.RESULTS:MRI showed ipsilateral abnormal enhancement in 54 patients (53%) revealing 46 lesions requiring excision (31 benign papillomas, 5 papillomas with atypia, 2 nipple adenomatosis, and 8 cancers) and 8 benign lesions not requiring excision. No suspicious enhancement was found in the remaining 48 participants (47%). Forty-two were followed up at 1 year with spontaneous resolution of the discharge and six underwent surgery (revealing 2 benign papillomas). MRI diagnostic accuracy for the detection of a lesion requiring excision was as follows: sensitivity 96%, specificity 85%, positive predictive value 85%, and negative predictive value 96%.CONCLUSION:In patients with suspicious nipple discharge and normal mammogram and ultrasound, MRI demonstrates excellent performance to identify lesions for which excision is required. Normal MRI indicates it is safe to propose follow-up only management, thus avoiding unnecessary duct excision.TRIAL REGISTRATION:ClinicalTrials.gov NCT02819362 KEY POINTS: • Breast MRI can be useful for the management of patients with suspicious nipple discharge and negative mammogram and ultrasound. • MRI detected a lesion requiring excision in 46 participants (45%) with unexplained discharge. • If breast MRI is negative, follow-up is a safe alternative for these patients.

Colon cancer is one of the most common leading causes of death worldwide. Prognostic at an early stage is an efficient way to decrease mortality. The Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a Protein Disulfide Isomerase (PDI) is highly expressed in various solid tumours and is involved in tumour microenvironment-associated processes such as tumour growth, invasion and metastasis. This study aims at examining the expression of AGR2 protein in colon cancer as its prognostic value in such cancer remains inconclusive.AGR2 protein expression was determined using immunohistochemistry on human tissue samples issued from a cohort of 82 colorectal carcinomas (Institut Bergonié, Bordeaux, France).AGR2 protein expression was significantly higher in tumours than in adjacent non-tumour controls. AGR2 expression subgroup analyses indicated that AGR2 low expression in colon cancer patients was significantly associated with worse overall survival. Mucinous colon cancers exhibited higher AGR2 expression levels than non-mucinous cancers. Additionally, tumours with microsatellite instability (MSI) were characterised by a strong upregulation of AGR2 mRNA and protein expression despite an absence of MLH1/MSH2 mutations.Our findings indicate that high AGR2 protein expression is correlated with longer patient survival and that AGR2 overexpression is associated with MSI and mucinous-type colorectal cancers. Overall, AGR2 might serve as a biomarker to stratify colon tumours and to contribute to the prognosis of colon cancer patients.

444 Background: Guidelines do not recommend FDG-Positron Emission Tomography (PET) Computed Tomography (CT) for the staging of Muscle Invasive Bladder Cancer (MIBC), but rather CT scan for lymph node (LN) and metastatic staging, despite its low accuracy. We performed a retrospective analysis of patients (pts) with MIBC who had a FDG-PET CT for staging, indicated by multidisciplinary team, in two centers, and analyzed its utility in this setting. Methods: All pts who had a FDG-PET CT performed at the time of diagnosis of MIBC from 01/2005 to 12/2017 in Bordeaux (Bergonie Institute and University Hospital) were retrospectively reviewed. Nodal and metastatic staging on CT and FDG-PET CT were done independently according to the 8th TNM classification. The aims of the study were to evaluate the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification (neoadjuvant chemotherapy for curative intent, no surgery for metastatic disease), according to FDG-PET CT results. Results: Among the 130 pts included, with a median age of 65 years, 74% were considered free from nodal metastasis (N0) by CT whereas only 44% were N0 from FDG-PET CT. Based on CT results, 88% of pts were free from distant metastasis (M0) but only 75% were classified M0, on FDG-PET CT. Accuracy of LN staging for CT and FDG-PET CT at initial diagnosis were analyzed for 85 pts (including 70 pts treated with neoadjuvant chemotherapy) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (respectively 80.8% versus 26.9%) but the specificity was low (respectively 54.2% versus 83.1%). Youden index was better for FDG-PET CT (0.35; 0.1 for CT), being more accurate for determining LN staging of MIBC. FDG-PET CT findings allowed a treatment decision modification in 34/130 pts (26.1%): therapeutic intensification in 12 pts (9.2%), including surgery not previously indicated, modified radiotherapy; or de-escalation in 22 pts (16.9%), mostly avoiding surgery. Conclusions: FDG-PET CT is more sensitive to detect LN involvement at initial diagnosis of MIBC than standard CT scan. Moreover, in the present study, treatment decisions were modified, according to FDG-PET CT results, in a quarter of pts according to LN and distant metastatic staging.

Background: Prostate cancer (PCa) is associated with high skeletal morbidity especially vertebral compression fractures (VCF) occurring on bone loss. We aimed to characterize benign (bVCF) versus malignant VCF (mVCF), in PCa patients who underwent vertebroplasty, and describe respective populations. Methods: An observational retrospective study was conducted in two French cancer centers. Characterization of VCF was made using a composite criterion (bone scan, CT scan, MRI +/- bone biopsy). Results: From 2008 to 2016, 100 patients, mean age 73.5 (45-94) and 128 VCFs were reported: 66 (52%) mVCF and 62 (48%) bVCF. Among bVCF, 17 (27%) occured in bone metastatic patients. Among mVCF, 28 (42%) of bone metastases were purely osteolytic and 38 (58%) with osteolytic component. Regarding bVCF, continuous androgen deprivation therapy and high doses of corticosteroids (> 6 months, ≥7.5 mg/day prednisone equivalent) were given in respectively 85% and 24% of cases. Dual X-ray Absorptiometry was performed in 13% of pts. Vitamin D supplementation was prescribed in 38% of patients. Conclusion: These data suggest the necessary prevention of bVCF even in patients with bone metastases with consequences on patient management, while studies for bone targeted agents approval used skeletal related events with no definition of the cause, i.e. benign or malignant. Occurrence of bVCF is a rising concern since these pts are experiencing longer survival. Malignant VCF were mostly with osteolytic component, which constitutes one feature of rising dedifferentiated phenotype. Vertebroplasty may play a major role in these newly defined populations.