Towards the identification of new biomarkers to better predict response to neoadjuvant chemotherapy in breast cancers

Early breast cancer (BC) concerns the majority of patients with BC, and is curable using multimodal treatments including neoadjuvant chemotherapy (NAC). Nevertheless, 20% of the patients will relapse in the years following the diagnosis. There is a need for predictive biomarkers of early BC response to NAC since it has been proven that response to NAC was correlated with improved outcomes. Finding predictive biomarkers is important for better patient selection and to tailor chemotherapy treatment. Moreover, better understanding underlying mechanisms related to non-response to NAC and metastases development in early BC could help to define new therapeutic avenues that could prevent BC relapse. In this work, one project was dedicated to the exploration of new predictive biomarkers (NACATS trials) in relation with EMT and TILs, and two other projects were related to metabolism exploration of early triple negative BC models (in 2D and 3D) and the targeting of metabolism pathways.Le cancer du sein précoce est curable grâce à l’utilisation de traitements multimodaux, dont la chimiothérapie néoadjuvante (NAC). Néanmoins, 20% des patients vont rechuter dans les années suivant le diagnostic. Trouver des biomarqueurs prédictifs de réponse à la NAC est essentiel puisqu’il a été prouvé que cette réponse était corrélée à une meilleure survie. Ces biomarqueurs sont importants pour une meilleure sélection des patients, mais aussi pour ajuster le traitement de manière personnalisée. De plus, mieux comprendre les mécanismes sous-jacents à la non-réponse à la NAC et à la rechute du cancer du sein précoce permettrait de définir de nouvelles pistes thérapeutiques afin d’éviter cette rechute. Durant cette thèse, un projet était dédié à la recherche de nouveaux biomarqueurs prédictifs de réponse à la NAC (étude NACATS) en relation avec l’EMT et les TILs et deux autres projets ont permis l’étude du métabolisme de modèles 2D et 3D de cancers du sein précoces et le ciblage de ces voies métaboliques.(MED - Sciences médicales) -- UCL, 202

Cutaneous metastasis in cervix cancer [L’image du mois. Métastases cutanées secondaires à un cancer du col de l’utérus]

Cutaneous metastases from cervix cancer are rarely described, and can appear years after a complete remission of the cancer. They may have multiple presentation as nodules, papules or telangiectasies. Unfortunately, these are associated with poor prognosis. We here report the case of a woman who developed cutaneous metastasis in the situation of a cervix cancer that appears to be stable under bevacizumab. Les métastases cutanées provenant du cancer du col de l’utérus sont rarement décrites, et peuvent apparaître plusieurs années après une rémission complète du cancer. Elles peuvent avoir plusieurs types de présentations telles que : nodules, papules, télangiectasies. Malheureusement, ces dernières sont associées à un mauvais pronostic. Nous rapportons le cas d’une patiente qui a développé des métastases cutanées alors que son cancer primitif était stable sous traitement par bévacizumab

Epithelioid angiosarcoma arising after an endovascular aneurysm repair: case report and review of the literature.

OBJECTIVES: We report the case of a 68-year-old male who was hospitalized for suspicion of endoleak and thrombosis of an aortic endoprosthesis, arising after multiple endovascular interventions during the last few months. During the intervention, amass was discovered, and biopsies were made. The anatomopathology results were in favor of an epithelioid angiosarcoma with atypical expression of CD31 and ERG- and no amplification of c-MYC. The main objective of this review is to highlight the difficulty of differential diagnosis, but also to evaluate overall survival according to treatments. METHODS: We performed a large review of the literature using PubMed for reports concerning angiosarcoma arising from Dacron grafts from 1981 to 2019. Articles presenting potentially relevant studies were read and analyzed. RESULTS: In our review, most of the patients were male (10 cases over 11 described), with amedian age of 63 years old (50-84 years old, 11 cases described). The overall interval time for the diagnosis after the endoprosthesis placement was 7.8 years (from 3.5 years to 17 years, 10 cases with the description) and the overall survival was 5 months (from 0 to 10 months, the only patient alive is not included, and only 8 cases had the description). CONCLUSION: In most of the reviewed cases, there was no information concerning immunohistochemistry. Biopsies remain the standard for the diagnosis with immunochemistry and molecular test to avoid amisdiagnosis. Epithelioid angiosarcomas derived from Dacron grafts are a rare entity, which are difficult to diagnose because of the paucity of cases. Prognosis is poor, even if surgical option is possible

Primary infectious costochondritis due to Prevotella nigrescens in an immunocompetent patient: clinical and imaging findings.

Infection of costal cartilage is a rare observation. We report the case of a 43-year-old male patient without relevant history who presented with a progressive painful swelling of the left chest wall since 4 months. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated an abscess within the left ninth costal cartilage with surrounding reactive changes. A CT-guided biopsy was performed and the culture of the sample revealed the presence of Prevotella nigrescens. Musculoskeletal infections by Prevotella are rarely described in the literature, Prevotella oralis and Prevotella bivia being the most frequently observed pathogens. These infections usually originate from a hematogenous spread after thoracic surgery or dental procedure. In our patient, conservative treatment was chosen. A clinical improvement was noted after 1-month antibiotherapy, confirmed by short-term and 6-month imaging follow-up showing the complete disappearance of all previously observed abnormalities

When a metastatic breast cancer is mimicking a pancreatic cancer: case report and review of the literature.

We report the case of a 51 year-old female who complained of jaundice and weight loss. At the time of presentation, she had been in remission from a stage 2a ductal breast carcinoma for 58 months. The clinical presentation was suggestive of a primary pancreas cancer with liver metastases and retroperitoneal lymph nodes. We performed liver and pancreas biopsies that demonstrate a relapse of her old breast carcinoma with positive hormone receptors and HER2 positive. Conservative treatment by chemotherapy was given with Paclitaxel - Trastuzumab and Pertuzumab. Pancreatic metastases are uncommon. Furthermore, pancreatic metastases from breast cancer are very rare. We performed a review of the literature and found 48 cases of pancreatic metastases from breast cancer. We would like to highlight by this case that when a pancreatic lesion appears, in patients with a past history of cancer, physicians must not forget the possibility of metastases from primary tumor even if the initial stage, of the tumor, is low. However the diagnosis is not always easy. If liver and pancreatic lesions occur simultaneously, the clinical presentation can mimic metastatic primary pancreatic cancer. Therefore performing biopsy is highly recommended for making the correct diagnosis and also for the staging of the disease and the choice of the best treatment according to immunohistochemical analysis

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine.

Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy

Tumor apelin and obesity are associated with reduced neoadjuvant chemotherapy response in a cohort of breast cancer patients

Obesity is a known factor increasing the risk of developing breast cancer and reducing disease free survival. In addition to these well-documented effects, recent studies have shown that obesity is also affecting response to chemotherapy. Among the multiple dysregulations associated with obesity, increased level of the apelin adipokine has been recently shown to be directly involved in the association between obesity and increased breast cancer progression. In this study, we analyzed in a retrospective cohort of 62 breast cancer patients the impact of obesity and tumoral apelin expression on response to neoadjuvant chemotherapy. In the multivariate logistic regression, obesity and high tumoral apelin expression were associated with a reduced response to NAC in our cohort. However, obesity and high tumoral apelin expression were not correlated, suggesting that those two parameters could be independently associated with reduced NAC response. These findings should be confirmed in independent cohorts