Diagnostic and predictive accuracy of anti-mullerian hormone for ovarian function after chemotherapy in premenopausal women with early breast cancer.

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.

Analyses of the Rationale and Implementation of Research Biopsies in Oncology Clinical Trials at a Tertiary Cancer Center.

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.

TERT Promoter Alterations in Glioblastoma: A Systematic Review.

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.

Impact of Taxanes, Endocrine Therapy, and Deleterious Germline BRCA Mutations on Anti-müllerian Hormone Levels in Early Breast Cancer Patients Treated With Anthracycline- and Cyclophosphamide-Based Chemotherapy.

Background: Limited evidence exists on the impact of adding a taxane, using endocrine therapy and carrying a deleterious germline BRCA mutation on ovarian reserve measured by anti-müllerian hormone (AMH) levels of young breast cancer patients receiving (neo)adjuvant cyclophosphamide- and anthracycline-based chemotherapy. Methods: This is a biomarker analysis including young (≤ 40 years) early breast cancer patients with known germline BRCA mutational status and available prospectively collected frozen plasma samples before and after chemotherapy. Chemotherapy consisted of either six cycles of FEC (5 fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) or three cycles of FEC followed by three cycles of docetaxel (D, 100 mg/m2). Endocrine therapy consisted of tamoxifen (±GnRH agonists). AMH levels at baseline, 1 and 3 years after diagnosis were compared according to type of chemotherapy (FEC only vs. FEC-D), use of endocrine therapy (yes vs. no) and deleterious germline BRCA mutations (mutated vs. negative). Results: Out of 148 included patients, 127 (86%) received D following FEC chemotherapy, 90 (61%) underwent endocrine therapy, and 35 (24%) had deleterious germline BRCA mutations. In the whole cohort, AMH levels drastically dropped 1 year after diagnosis (p < 0.0001) with a slight but significant recovery at 3 years (p < 0.0001). One year after diagnosis, patients treated with FEC only had higher median AMH levels than those who received FEC-D (0.22 vs. 0.04 µg/L, p = 0.0006); no difference was observed at 3 years (0.06 and 0.18 µg/L, p = 0.47). Patients under endocrine therapy had significantly higher AMH levels than those who did not receive this treatment 1 year after diagnosis (0.12 vs. 0.02 µg/L; p = 0.008), with no difference at 3 years (0.11 and 0.20 µg/L, p = 0.22). AMH levels were similar between BRCA-mutated and BRCA-negative patients at baseline (1.94 vs. 1.66 µg/L, p = 0.53), 1 year (0.09 vs. 0.06 µg/L, p = 0.39) and 3 years (0.25 vs. 0.16 µg/L; p = 0.43) after diagnosis. Conclusions: In breast cancer patients receiving FEC chemotherapy, adding D appeared to negatively impact on their ovarian reserve in the short-term; no further detrimental effect was observed for endocrine therapy use and presence of a deleterious germline BRCA mutation.