Eccrine Porocarcinoma: A Challenging Diagnostic and Therapeutic Tumoral Entity

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines

Prise en charge du cancer du col de l’utérus métastatique et/ou en rechute

International audienceThe prognosis of metastatic or recurrent cervical cancer remains dismal. The poor chemosensitivity of this tumor- is an issue, especially in case of recurrence in irradiated fields. Still, chemotherapy has shown some efficacy, and mostly consists in platinum-based doublets. The addition of bevacizumab to chemotherapy has been recently validated. However, most of these patients present with complex clinical situations and the treatment strategy has to be discussed in multidisciplinary tumor boards.Le pronostic des cancers du col utérin d’emblée métastatiques ou récidivants est particulièrement péjoratif. Ces tumeurs sont peu chimio-sensibles, surtout si elles surviennent dans une zone préalablement irradiée. En cas d’indication de chimiothérapie, les protocoles proposés sont le plus souvent des doublets comportant du platine. L’indication de l’association de bévacizumab à ces protocoles de chimiothérapie représente le progrès le plus récent dans la prise en charge de cette affection. La complexité des présentations cliniques et de la stratégie de prise en charge requiert une discussion des dossiers au cas par cas, en réunion de concertation pluridisciplinaire

Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer

In this review article, we present the current knowledge on PTPN13, a class I non-receptor protein tyrosine phosphatase identified in 1994. We focus particularly on its role in cancer, where PTPN13 acts as an oncogenic protein and also a tumor suppressor. To try to understand these apparent contradictory functions, we discuss PTPN13 implication in the FAS and oncogenic tyrosine kinase signaling pathways and in the associated biological activities, as well as its post-transcriptional and epigenetic regulation. Then, we describe PTPN13 clinical significance as a prognostic marker in different cancer types and its impact on anti-cancer treatment sensitivity. Finally, we present future research axes following recent findings on its role in cell junction regulation that implicate PTPN13 in cell death and cell migration, two major hallmarks of tumor formation and progression

High PTPN13 expression in high grade serous ovarian carcinoma is associated with a better patient outcome

International audienceBackground:Chromosome 4q loss of heterozygosity (LOH) is frequently observed in high-grade serous ovarian carcinoma (HGSOC). However, this LOH has not been clearly associated with the inactivation of any tumor suppressor gene(s). As the tumor suppressor gene PTPN13 is located on chromosome 4q21, we investigated its expression in HGSOC.Methods:PTPN13 protein expression was investigated by immunohistochemistry (IHC) in normal ovary epithelium and in 30 HGSOC samples, whereas PTPN13 mRNA expression was quantified by RT-PCR in another independent cohort of 28 HGSOC samples. Patients in both cohorts were followed for more than 8.5 years.Results:PTPN13 protein expression was lower in one third of HGSOC samples compared with normal ovary epithelium. In both cohorts, high PTPN13 expression level (mRNA or protein) in the tumor was associated with favorable outcome and significantly longer survival (HR=0.27; p=0.0087 and HR=0.42; p=0.03, respectively).Conclusion:This study demonstrates, for the first time, that high PTPN13 expression level is a prognostic indicator of favorable outcome in patients with HGSOC. This finding, in conjunction with our previous mechanistic studies, suggests that PTPN13 loss, possibly by 4q LOH, enhances HGSOC aggressiveness and highlight the interest of studying PTPN13 signaling in HGSOC to identify new potential therapeutic targets

Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help?

International audienceThe decision to administer adjuvant chemotherapy in treatment of early invasive breast cancer (EBC) is often complex, particularly for hormone receptor-positive (HR+) diseases, and current guidelines often classify these patients in an intermediate-risk group. Several biomarkers are currently available in this indication, in order to obtain additional and more accurate prognostic information compared to classic clinicopathological characteristics and guide the indication of adjuvant chemotherapy, optimizing the efficacy/toxicity ratio. We conducted a systematic review to evaluate the clinical validity and clinical utility of five biomarkers (uPA/PAI-1, OncotypeDX®, MammaPrint®, PAM50, and EndoPredict®) in HR+/HER2- EBC, whatever the nodal status. A total of 89 studies met the inclusion criteria. Even though data currently available confirm the clinical validity of these biomarkers, there is a lack of data regarding clinical utility for most of them. Prospective studies in well-defined populations are needed to integrate these biomarkers in a decision strategy

A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy

Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0–62.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy

Changes in vitamin D and calcium metabolism markers in patients undergoing adjuvant chemotherapy for breast cancer

International audienceBackground: Changes in calcium metabolism and calcium urinary excretion during chemotherapy have not been thoroughly assessed in patients with early breast cancer (EBC), a population who frequently present vitamin D insufficiency. As hypercalciuria is a classical contra-indication to vitamin D (VD) supplementation, this study evaluated changes in VD and calcium metabolism parameters in patients with EBC undergoing adjuvant chemotherapy (CT). Methods: In patients with EBC who received six cycles of adjuvant CT, VD and calcium parameters were monitored at inclusion, and then every 3 weeks, at each CT cycle initiation. The primary endpoint was the percentage of patients showing hypercalciuria during adjuvant CT (between Day 1, Cycle 1 [D1C1] and Day 1, Cycle 6 [D1C6]). Results: The primary endpoint could be evaluated in 82 patients. Most patients (n = 66, 80.5%) had VD insufficiency (< 30 ng/mL) at baseline. Hypercalciuria was detected in 29 patients (35.4%; 95% CI: 25.6-46.5) between D1C1 and D1C6, but was not clinically significant in any of the affected patients. The percentage of hypercalciuria events was not different between patients with sufficient and insufficient baseline VD levels (34.8% vs. 37.5%), and between patients who received or not VD supplementation (37.5% vs. 34.5%,). Conclusions: This comprehensive study on VD and calcium parameter changes in patients with EBC during adjuvant chemotherapy shows that hypercalciuria is a frequent abnormality in this setting, although asymptomatic. Therefore, it should not be considered as a limitation for high dose VD supplementation in this population

Differential Sensitivity of Germline and Somatic <i>BRCA</i> Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer

Purpose: The introduction of PARP inhibitors (PARPis) as a treatment option for patients with high-grade serous ovarian cancer (HGSOC) modified the approach of BRCA testing worldwide. In this study, we aim to evaluate the impact of BRCA1 and BRCA2 variants on treatment response and survival outcomes in patients diagnosed in our institution. Methods: A total of 805 HGSOC samples underwent BRCA1 and BRCA2 variant detection by using next-generation sequencing (NGS). Among them, a pathogenic alteration was detected in 104 specimens. Clinicopathological features and germline status were recovered, and alteration types were further characterized. The clinical significance of variant type in terms of response to chemotherapy and to PARPis as well as overall survival were evaluated using univariate analysis. Results: In our cohort, 13.2% of the HGSOC samples harbored a pathogenic BRCA1 or BRCA2 variant, among which 58.7% were inherited. No difference was observed between germline and somatic variants in terms of the gene altered. Interestingly, patients with somatic variants only (no germline) demonstrated better outcomes under PARPi treatment compared to those with germline ones. Conclusion: The determination of the inheritance or acquisition of BRCA1 and BRCA2 alterations could provide valuable information for improving management strategies and predicting the outcome of patients with HGSOC

Conditional Probability of Survival and Prognostic Factors in Long-Term Survivors of High-Grade Serous Ovarian Cancer

International audienceObjective: High-grade serous ovarian cancers (HGSOC) are heterogeneous, often diagnosed at an advanced stage, and associated with poor overall survival (OS, 39% at five years). There are few data about the prognostic factors of late relapses in HGSOC patients who survived ≥five years, long-term survivors (LTS). The aim of our study is to assess the probability of survival according to the already survived time from diagnosis. Methods: Data from HGSOC patients treated between 1995 and 2016 were retrospectively collected to estimate the conditional probability of survival (CPS), probability of surviving Y years after diagnosis when the patient had already survived X years, and to determine the LTS prognostic factors. The primary endpoint was OS. Results: 404 patients were included; 120 of them were LTS. Patients were aged 61 years (range: 20–89), WHO performance status 0–1 in 86.9% and 2 in 13.1%, and Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging III and IV in 82.7% and 17.3% patients. Breast cancer (BRCA) status was available in 116 patients (33% mutated), including 58 LTS (36% mutated). No macroscopic residual disease was observed in 58.4% patients. First-line platinum-based chemotherapy plus paclitaxel was administered in 80.4% of patients (median: six cycles (range: 1–14)). After a 9 point 3-year follow-up, median OS was four years (95% CI: 3.6–4.5). The CPS at five years after surviving one year was 42.8% (95% CI: 35.3–48.3); it increased to 81.7% (95% CI: 75.5–87.8) after four survived years. Progression-free interval>18 months was the only LTS prognostic factor in the multivariable analysis (hazard ratio (HR) = 0.23; 95% CI: 0.13–0.40; p < 0.001). Conclusion: The CPS provided relevant and encouraging clinical information on the life expectancy of HGSOC patients who already survived a period of time after diagnosis. LTS prognostic factors are useful for clinicians and patients