RESUMO
BACKGROUND: Current fertility preservation strategies for young breast cancer patients planning a future motherhood include the association of controlled ovarian stimulation with the aromatase inhibitor letrozole (let-COS) to harvest mature oocytes while maintaining low estradiol levels. Despite this is a widely adopted protocol, the safety of let-COS on breast cancer outcomes has been poorly investigated and its use remains off-label. We assessed the safety of let-COS in breast cancer patients using circulating tumor DNA (ctDNA) as a surrogate biomarker of disease recurrence. METHODS: BROVALE is an interventional non-randomized prospective study designed to evaluate the efficacy and safety of let-COS for fertility preservation in early breast cancer patients before starting (neo)adjuvant chemotherapy. Letrozole was administered throughout the COS cycle, until ovulation triggering. Safety was a secondary endpoint. Data on oncological outcomes were collected during the follow-up as well as plasma and whole blood for evaluation of ctDNA levels at the time of enrollment (i.e. before starting let-COS) and oocyte retrieval (i.e. 48 hours after the last administration of letrozole). Targeted gene sequencing on the primary tumor samples was performed to identify specific mutations used for ctDNA analysis by digital PCR. DNA extracted from whole blood samples was used to discriminate between somatic and germline mutations. RESULTS: From April 2014 to May 2017, 29 young early breast cancer patients enrolled in the BROVALE study who had available tissue samples participated to the ctDNA substudy. Among them, 15 had at least one validated somatic mutation. ctDNA was undetectable neither before nor after let-COS in 9 of them. Six patients had detectable ctDNA in the plasma samples collected before Let-COS. No change in ctDNA level after let-COS was observed in 3 patients and the level decreased (fold-change ≤ 0.5) in two women. One patient experienced an increased (fold-change ≥ 2) in ctDNA level but without disease relapse 34 months after diagnosis. CONCLUSIONS: No increase in ctDNA level was observed in 93% (14/15) of the patients receiving let-COS supporting its use as a safe strategy for young women with early breast cancer interested in fertility preservation before chemotherapy.
RESUMO
INTRODUCTION: Hemorrhagic cystitis (HC) is a well-recognized problem that is regularly observed after hematopoietic stem cell transplantation (HSCT). The published data does not report on the potential risk factors for the viral-induced HC that might require prophylactic treatments. PATIENTS AND METHODS: We conducted a retrospective analysis of all adult patients who underwent allogeneic HSCT at Jules Bordet Institute between 1992 and 2013. Our institutional protocol consists in monitoring the patient for signs and symptoms of HC on a daily basis during the initial admission for HSCT, then once weekly after discharge until 2 months thereafter. RESULTS: HC was found in 64 patients, of whom 56 (87.5%) had viral-induced HC. The median time between HSCT and HC was 39.5 days (range, 1-2766 days); the median time between detection of a viral infection and HC was 32 days (range, 0-2752 days). In multivariate analysis, HC is correlated to the infection with the BK virus (hazard ratio, 6.0; 95% confidence interval, 5.03-6.90; P = .0001) and the adenovirus (hazard ratio, 4.93; 95% confidence interval, 4.06-5.80; P = .0003). The 5-year overall survival of patients with HC was 36%. The 5-year survival rates were not statistically different between patients with or without HC (25% vs. 39%; P = .20). CONCLUSION: The presence of the identified risk factors should prompt closer follow-up with screening tests and preventive measures for BK virus and adenovirus infections in patients undergoing HSCT.