Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth. The aim of this systematic review is to provide an overview of the available data concerning TERT alterations and glioblastoma in terms of incidence, physiopathological understanding, and potential therapeutic implications.

Purpose: Accurate diagnosis and prediction of loss of ovarian function after chemotherapy for premenopausal women with early breast cancer (eBC) is important for future fertility and clinical decisions regarding the need for subsequent adjuvant ovarian suppression. We have investigated the value of anti-mullerian hormone (AMH) as serum biomarker for this. Methods: AMH was measured in serial blood samples from 206 premenopausal women aged 40–45 years with eBC, before and at intervals after chemotherapy. The diagnostic accuracy of AMH for loss of ovarian function at 30 months after chemotherapy and the predictive value for that of AMH measurement at 6 months were analysed. Results: Undetectable AMH showed a high diagnostic accuracy for absent ovarian function at 30 months with AUROC 0.89 (96% CI 0.84–0.94, P < 0.0001). PPV of undetectable AMH at 6 months for a menopausal estradiol level at 30 months was 0.77. In multivariate analysis age, pre-treatment AMH and FSH, and taxane treatment were significant predictors, and combined with AMH at 6 months, gave AUROC of 0.90 (95% CI 0.86–0.94), with PPV 0.79 for loss of ovarian function at 30 months. Validation by random forest models with 30% data retained gave similar results. Conclusions: AMH is a reliable diagnostic test for lack of ovarian function after chemotherapy in women aged 40–45 with eBC. Early analysis of AMH after chemotherapy allows identification of women who will not recover ovarian function with good accuracy. These analyses will help inform treatment decisions regarding adjuvant endocrine therapy in women who were premenopausal before starting chemotherapy.

Background Biomarkers in clinical trials have led to massive incorporation of research biopsies, with potentially risks and no direct benefit for patients. In 2018, the American Society of Clinical Oncology (ASCO) released an ethical framework to provide guidance on incorporating research biopsies in cancer clinical trials. Materials and Methods We collected biopsy requirements of cancer clinical trials conducted at Institut Jules Bordet (IJB) between 2015 and 2019 to examine adherence with the ASCO Ethical Framework. We used logistic regression models to test the association between the request for biopsy, the request for tissue, and the adherence to the ASCO framework as well as some trial characteristics. Results Between January 2015 and December 2019, 178 oncological studies were conducted at IJB. Of these, 138 (78%) were sponsored by industry, 132 (74%) were phase II and III studies, and 141 (79%) concerned metastatic disease. Tissue was required for inclusion for 119 (67%) studies, among which 59 required at least one new biopsy. Adherence to ASCO's Ethical Framework was 67% for studies requiring tissue and went down to 39% for studies requiring at least one new biopsy. In multivariate analysis, requests for tissue or new biopsies increased in early-phase studies (p < .001, p < .001, respectively) and in studies investigating innovative treatments (immunotherapy or targeted therapies; p < .01, p = .02). Compliance to the ASCO framework significantly decreased with time (p < .001) and in early-phase studies (p < .001). Conclusion Numerous studies required tissue or new biopsies for exploratory objectives of unknown clinical utility. Requests for tissue increased over the years, whereas compliance to ASCO's Ethical Framework decreased. Implications for Practice In 2019, the American Society of Clinical Oncology (ASCO) developed an ethical framework to provide guidance on incorporating research biopsies in clinical trials. This study underlines the growing request for tissue in clinical trials with potentially no impact on drug development and no benefit to actual or future patients. Adherence to ASCO's Ethical Framework decreases through time. These results highlight the importance of improving the ethics of research biopsies. ASCO's Ethical Framework offers an opportunity to improve quality of care in clinical research by maximizing scientific utility and allowing for clinically meaningful correlative science and safe access to innovative treatments for a maximum number of patients.

In the OlympiA trial, adjuvant olaparib improved survival in patients with germline BRCA1/BRCA2 mutations (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC). This analysis presents real-world data from the French-funded early access program for adjuvant olaparib. Eligible adults had gBRCAm and high-risk, HER2-negative eBC, and had received neoadjuvant/adjuvant chemotherapy plus local treatment. Data on olaparib dosing, adverse events (AEs), and health-related quality of life (QoL) were collected during the 12-month treatment period. Between March 2022 and September 2024, 320 treatment access requests were submitted, of which 308 were approved, with treatment for 217 of the 308 patients (70.5%) at a median follow-up of 10.1 months. Triple-negative tumors were reported in 182 of 308 patients (59.1%) and hormone receptor-positive/HER2-negative tumors in 126 (40.9%). Median age was 45 years (range, 24-82). Most treated patients (208 of 217; 95.9%) started olaparib at 300 mg twice daily. Treatment changes occurred in 139 of 217 patients (64.0%), including interruptions (73 of 217; 33.6%) and dose modifications (66 of 217; 30.4%). Treatment-related AEs occurred in 68 of 217 patients (31.3%), serious AEs in 19 of 217 (8.7%), and AE-related discontinuations in 22 of 217 (10.1%). Two non-olaparib-related deaths occurred and no myelodysplastic syndrome/acute myeloid leukemia was reported. QoL data were available for 85 patients at baseline, decreasing to 26 at month 12. Median global health status/QoL score remained stable throughout treatment. Disease recurrence occurred in 5 of 217 patients (2.3%). These real-world findings support adjuvant olaparib as standard-of-care in patients with gBRCAm and high-risk, HER2-negative eBC, with no new safety signals.