Endocrine Abstracts

Background: Skeletal fragility is an important clinical issue in women with early-stage breast cancer and men with non-metastatic prostate cancer under hormonal hormone deprivation therapies (HDTs). Vertebral fractures (VFs) have been reported in a remarkable number of subjects exposed to HDT especially when the diagnosis of fractures is performed by a radiological and morphometric approach. Notably, prediction of fractures in this clinical setting is a challenge and determina...

Background: Mitotane (o,p’DDD) is the reference therapy for adrenocortical carcinoma (ACC) and should undergo metabolization in o,p’DDE and o,p’DDA to exert its anti-proliferative activity. We have previously shown that there is a link between RRM1 gene expression and o,p’DDD activity in an adjuvant setting. Aim of this study was to assess whether RRM1 gene expression is correlated to the bioavailability and cytotoxic activity of o,p’DDD and its metabo...

Background: No randomized trials have been conducted in adrenocortical carcinoma (ACC) patients. Treatment recommendations for this rare but aggressive disease have been based on data from small phase II trials. We have now performed the first randomized phase III trial, comparing etoposide, doxorubicin, cisplatin, plus mitotane (EDP-M) against streptozotocin plus mitotane (Sz-M).Methods: Three-hundred and four chemotherapy-naive patients with ACC not am...

Objective: Seventeen patients (9 women, 8 men aged 36 years, 22–58) radically resected for ACC were treated with adjuvant mitotane and prospectically followed from 2000 to 2006.Methods: Stage of ACC: was: 1 stage I,; 12 stage II, 4 stage III; Weiss score 6, 3–9; Ki67% 20, 4–67. Eleven patients had functional tumors. Median duration of treatment was 15 months (range:4–84) and 14 patients are currently on mitotane, 2 died, 1 discontinue...

Background: Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. The Fibroblast Growth Factor/Fibroblast Growth Factor Receptor (FGF/FGFR) pathway plays a role in both embryogenesis and tumorigenesis of adrenal gland. Our group demonstrated that FGFR1-4 were upregulated in ACCs and that their high expression was significantly associated with worse prognosis, suggesting that they are potentially interesting therapeutic targets.<p class="abste...

Bone loss is a frequent complication of aromatase inhibitors (AIs) therapy in women with breast cancer. Bone-active drugs are effective in protecting the skeleton from detrimental actions of AIs. However, bone mineral density (BMD) was the primary end-point in most of published studies, whereas data on fractures were scant and mainly limited to denosumab. In this prospective study, we investigated the effects of denosumab, oral bisphosphonates and intravenous zoledronate on ri...

Background: Adrenocortical carcinoma (ACC) is a rare cancer associated with hereditary syndromes in 10% of cases. However, data on germline variants (GVs) in adult patients with sporadic ACC are limited.Methods: We analyzed germline DNA from 150 adult patients with sporadic ACC sequentially referred to our centers between 1998-2019. We designed a custom panel of 17 genes potentially involved in the pathogenesis of ACC: AIP, APC, ARMC5, ARNT, BRCA1, BRCA2...

Purpose: Mitotane is the reference systemic therapy for adrenocortical carcinoma (ACC), but its mechanism of action and possible predictors of treatment response remain poorly defined. Our aim was to evaluate the gene expression of ribonucleotide reductase large subunit 1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) in ACC as potential biomarkers for clinical outcome and response to mitotane.Experimental design: Forty-five and 47 tiss...

We have demonstrated that adjuvant mitotane prolong recurrence free survival (RFS) in patients with radically resected ACC. Aim of the present study was to correlate mitotane levels with patient outcome in an adjuvant setting in 3 different referral centres in Europe. There were 120 patients (45 W, 75 M, median age 44 years, range 16–76) radically resected for ACC who were treated adjuvantly with mitotane from 1996 to 2010. ACC was stage I in 10 cases, II in 73, III in 31...

Introduction: O,p’DDD is the drug of choice for patients with adrenocortical carcinoma (ACC). Monitoring o,p’DDD serum level has been proposed as predictor of tumour response. Measurement of o,p’DDD metabolites involved in the active pathway may provide an improved prediction of o,p’DDD activity. The objective of our study was to (1)to confirm the currently used threshold o,p’DDD serum level of 14mg/l for achieving a tumour response and (2)compare the ...