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

The 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.

Quantification of Immune Variables from Liquid Biopsy in Breast Cancer Patients Links Vδ2 γδ T Cell Alterations with Lymph Node Invasion.

The rationale for therapeutic targeting of Vδ2 γδ T cells in breast cancer is strongly supported by in vitro and murine preclinical investigations, characterizing them as potent breast tumor cell killers and source of Th1-related cytokines, backing cytotoxic αβ T cells. Nonetheless, insights regarding Vδ2 γδ T cell phenotypic alterations in human breast cancers are still lacking. This paucity of information is partly due to the challenging scarcity of these cells in surgical specimens.

When to do surgical resection for atypical breast lesions: Results of a prospective cohort of 518 lesions.

Aim: There is no consensual indication for surgical resection after diagnosis on per-cutaneous biopsy of borderline breast lesions (B3). We evaluate under-evaluation rate of per-cutaneous biopsy and predictive factors of under-evaluation. We analyze accuracy of reported decision-making tools.

[GEFPICS' guidelines for management of breast cancer tissue samples in the neoadjuvant setting].

Neoadjuvant 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.

Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ.

Background: Tumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Thus, it has been suggested that TIL density or/and immunophenotype could serve as biomarkers for selection of IBC patients for immunotherapy. However, much less is known about significance of TILs in breast ductal carcinoma in situ (DCIS).

promoter status and gene copy number gains: effect on expression and association with prognosis in breast cancer.

Upregulation of the telomerase reverse transcriptase () gene in human cancers leads to telomerase activation, which contributes to the growth advantage and survival of tumor cells. Molecular mechanisms of upregulation are complex, tumor-specific and can be clinically relevant. To investigate these mechanisms in breast cancer, we sequenced the promoter, evaluated copy number changes and assessed the expression of the oncogene, a known transcriptional regulator, in two breast cancer cohorts comprising a total of 122 patients.

Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

Purpose: This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox).

Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept.

To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel).

[Pre-analytical stage for biomarker assessment in breast cancer: 2014 update of the GEFPICS' guidelines in France].

Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked.

[2014 update of the GEFPICS' recommendations for HER2 status determination in breast cancers in France].

International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse.

Small rigid platforms functionalization with quaternary ammonium: targeting extracellular matrix of chondrosarcoma.

Unlabelled: This work takes place in the "cartilage targeting strategy", consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PGs) of extracellular matrix (ECM). The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with (111)Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm rat chondrosarcoma (SRC) orthotopic model.

[Diagnostic approach for breast cancer classification].

The pathologist is involved at various steps in the management of a patient with breast cancer and in the therapeutic decision. First, the pathologist confirms a diagnosis of malignancy on cytology specimens, microbiopsies and surgical specimens. During the surgery, through the frozen section, the pathologist specifies the surgical limits and collects specimens for research purposes.

99mTc-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model.

Background: Since proteoglycans (PGs) appear as key partners in chondrosarcoma biology, PG-targeted imaging using the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) developed by our group was previously demonstrated to be a good single-photon emission computed tomography tracer for cartilage neoplasms. We therefore initiated this new preclinical study to evaluate the relevance of 99mTc-NTP 15-5 imaging for the in vivo monitoring and quantitative assessment of chondrosarcoma response to zoledronic acid (ZOL) in the Swarm rat orthotopic model.

Findings: Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 μg/kg, subcutaneously) or phosphate-buffered saline, twice a week, from day 4 to day 48 post-tumor implantation.

Embolization and endothelial ablation with chitosan and sodium sotradecol sulfate: preliminary results in an animal model.

Purpose: To investigate whether embolization with chitosan hydrogel (CH) with or without a sclerosant (sodium tetradecyl sulphate, STS) can induce chemical endothelial ablation and prevent endothelial recanalization in a rabbit model.

Methods: Chitosan radiopaque thermogels were prepared using chitosan, β-glycerophosphate, iopamidol, and different STS concentrations. Each auricular artery of 14 New Zealand White rabbits was cannulated and injected with 0.

Relevance of the POS-1 orthotopic model as an "imaging model" for in vivo and simultaneous monitoring of tumor proliferation and bone remodeling in osteosarcoma.

Introduction: Osteosarcoma (OS) management requires a better understanding of tumor/bone interactions in vivo during disease progression. Using [(18)F]-FDG and [(99m)Tc]-HMDP imaging, we assessed a methodology for an in vivo quantitative characterization of an orthotopic model of osteolytic OS on the basis of (1) tumor proliferation, (2) tumor and bone metabolic activities, and (3) bone remodeling.

Methods: POS-1 tumor bearing mice were monitored in vivo over a 26-day period, with tumor and bone metabolic volumes (TMV and BMV, respectively) being determined from [(18)F]-FDG, bone remodeling from [(99m)Tc]-HMDP, and tumoral volume from micro- computed tomography scans.

Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies.

Cartilage tumours present ongoing therapeutic challenges due to their chondrogenic extracellular matrix that potentially hampers drug delivery, their low percentage of dividing cells, and their poor vascularity. In this context, and based on the affinity of the quaternary ammonium moiety for proteoglycans (PG), we developed a strategy that uses the quaternary ammonium function to selectively deliver DNA alkylating agents to the cartilage tumour tissue. We engineered the quaternary ammonium derivative of melphalan (Mel-AQ) and assessed its antitumoural activity in vitro and in vivo.

A"Proteoglycan targeting strategy" for the scintigraphic imaging and monitoring of the swarm rat chondrosarcoma orthotopic model.

Our lab developed (99m)Tc-NTP 15-5 radiotracer as targeting proteoglycans (PGs) for the scintigraphic imaging of joint. This paper reports preclinical results of (99m)Tc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC). (99m)Tc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume.

Ovarian epithelial dysplasia and prophylactic oophorectomy for genetic risk.

Unlabelled: To make an accurate histopathological description of ovarian dysplasia in a population at genetic risk of ovarian cancer and devise an ovarian dysplasia score.

Materials And Methods: In this retrospective cohort study, 90 patients who had undergone bilateral oophorectomy or ovarian cystectomy between 1992 and 2005 and whose ovaries were reported as normal were divided into two groups: Group A comprising prophylactic oophorectomies for genetic predisposition (N = 28), and Group B or control group, fertile and non-cancerous (N = 62). Eleven epithelial cytological and architectural features were defined.

[Classification of preinvasive breast and carcinoma in situ: doubts, controversies, and proposal for new categorizations].

As a consequence of increased screening mammography, preinvasive breast lesions represent a growing percentage of breast pathology diagnoses. Intraductal epithelial proliferations of the breast are, at present, classified into three groups: usual epithelial hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. The boundary between those two last entities is not clearly defined on a morphological point of view although the clinical management is different.