Is it safe to perform controlled ovarian stimulation (COS) for fertility preservation before starting anticancer therapies or ART after treatments in young breast cancer patients?
Performing COS ...before, or ART following anticancer treatment in young women with breast cancer does not seem to be associated with detrimental prognostic effect in terms of breast cancer recurrence, mortality or event-free survival (EFS).
COS for oocyte/embryo cryopreservation before starting chemotherapy is standard of care for young women with breast cancer wishing to preserve fertility. However, some oncologists remain concerned on the safety of COS, particularly in patients with hormone-sensitive tumors, even when associated with aromatase inhibitors. Moreover, limited evidence exists on the safety of ART in breast cancer survivors for achieving pregnancy after the completion of anticancer treatments.
The present systematic review and meta-analysis was carried out by three blinded investigators using the keywords 'breast cancer' and 'fertility preservation'; keywords were combined with Boolean operators. Eligible studies were identified by a systematic literature search of Medline, Web of Science, Embase and Cochrane library with no language or date restriction up to 30 June 2021.
To be included in this meta-analysis, eligible studies had to be case-control or cohort studies comparing survival outcomes of women who underwent COS or ART before or after breast cancer treatments compared to breast cancer patients not exposed to these strategies. Survival outcomes of interest were cancer recurrence rate, relapse rate, overall survival and number of deaths. Adjusted relative risk (RR) and hazard ratio (HR) with 95% CI were extracted. When the number of events for each group were available but the above measures were not reported, HRs were estimated using the Watkins and Bennett method. We excluded case reports or case series with <10 patients and studies without a control group of breast cancer patients who did not pursue COS or ART. Quality of data and risk of bias were assessed using the Newcastle-Ottawa Assessment Scale.
A total of 1835 records were retrieved. After excluding ineligible publications, 15 studies were finally included in the present meta-analysis (n = 4643). Among them, 11 reported the outcomes of breast cancer patients who underwent COS for fertility preservation before starting chemotherapy, and 4 the safety of ART following anticancer treatment completion. Compared to women who did not receive fertility preservation at diagnosis (n = 2386), those who underwent COS (n = 1594) had reduced risk of recurrence (RR 0.58, 95% CI 0.46-0.73) and mortality (RR 0.54, 95% CI 0.38-0.76). No detrimental effect of COS on EFS was observed (HR 0.76, 95% CI 0.55-1.06). A similar trend of better outcomes in terms of EFS was observed in women with hormone-receptor-positive disease who underwent COS (HR 0.36, 95% CI 0.20-0.65). A reduced risk of recurrence was also observed in patients undergoing COS before neoadjuvant chemotherapy (RR 0.22, 95% CI 0.06-0.80). Compared to women not exposed to ART following completion of anticancer treatments (n = 540), those exposed to ART (n = 123) showed a tendency for better outcomes in terms of recurrence ratio (RR 0.34, 95% CI 0.17-0.70) and EFS (HR 0.43, 95% CI 0.17-1.11).
This meta-analysis is based on abstracted data and most of the studies included are retrospective cohort studies. Not all studies had matching criteria between the study population and the controls, and these criteria often differed between the studies. Moreover, rate of recurrence is reported as a punctual event and it is not possible to establish when recurrences occurred and whether follow-up, which was shorter than 5 years in some of the included studies, is adequate to capture late recurrences.
Our results demonstrate that performing COS at diagnosis or ART following treatment completion does not seem to be associated with detrimental prognostic effect in young women with breast cancer, including among patients with hormone receptor-positive disease and those receiving neoadjuvant chemotherapy.
Partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant number MFAG 2020 ID 24698) and the Italian Ministry of Health-5 × 1000 funds 2017 (no grant number). M.L. acted as consultant for Roche, Pfizer, Novartis, Lilly, AstraZeneca, MSD, Exact Sciences, Gilead, Seagen and received speaker honoraria from Roche, Pfizer, Novartis, Lilly, Ipsen, Takeda, Libbs, Knight, Sandoz outside the submitted work. F.S. acted as consultant for Novartis, MSD, Sun Pharma, Philogen and Pierre Fabre and received speaker honoraria from Roche, Novartis, BMS, MSD, Merck, Sun Pharma, Sanofi and Pierre Fabre outside the submitted work. I.D. has acted as a consultant for Roche, has received research grants from Roche and Ferring, has received reagents for academic clinical trial from Roche diagnostics, speaker's fees from Novartis, and support for congresses from Theramex and Ferring outside the submitted work. L.D.M. reported honoraria from Roche, Novartis, Eli Lilly, MSD, Pfizer, Ipsen, Novartis and had an advisory role for Roche, Eli Lilly, Novartis, MSD, Genomic Health, Pierre Fabre, Daiichi Sankyo, Seagen, AstraZeneca, Eisai outside the submitted work. The other authors declare no conflict of interest. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.
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An extended treatment of microcalorimeters functioning including large signal analysis reveals some important aspects that have never been described before. Outside the small signal approximation, ...transition edge sensors have a non linear response which needs to be studied and understood. This is accomplished in this paper. Furthermore, the electrothermal feedback shortens the recovery time which cannot be anymore described by a unique decay time, since during the restoring process it changes considerably with the temperature inside the sensor transition.
We examine the sensitivity of a large scale two-phase liquid argon detector to the directionality of the dark matter signal. This study was performed under the assumption that, above 50 keV of recoil ...energy, one can determine (with some resolution) the direction of the recoil nucleus without head-tail discrimination, as suggested by past studies that proposed to exploit the dependence of columnar recombination on the angle between the recoil nucleus direction and the electric field. In this paper we study the differential interaction recoil rate as a function of the recoil direction angle with respect to the zenith for a detector located at the Laboratori Nazionali del Gran Sasso and we determine its diurnal and seasonal modulation. Using a likelihood-ratio based approach we show that, with the angular information alone, 100 (250) events are enough to reject the isotropic hypothesis at three standard deviation level, for a perfect (400 mrad) angular resolution. For an exposure of 100 tonne years this would correspond to a spin independent WIMP-nucleon cross section of about 10−46cm2 at 200 GeV WIMP mass. The results presented in this paper provide strong motivation for the experimental determination of directional recoil effects in two-phase liquid argon detectors.
We present first significant limits on WIMP dark matter by the phonon-light technique, where combined phonon and light signals from a scintillating cryogenic detector are used. Data from early 2004 ...with two 300g CRESST-II prototype detector modules are presented, with a net exposure of 20.5kg days. The modules consist of a CaWO4 scintillating “target” crystal and a smaller cryogenic light detector. The combination of phonon and light signals leads to a strong suppression of non-nuclear recoil backgrounds. Using this information to define an acceptance region for nuclear recoils we have 16 events from the two modules, corresponding to a rate for nuclear recoils between 12 and 40keV of (0.87±0.22) events/(kgday). This is compatible with the rate expected from neutron background, and most of these events lie in the region of the phonon-light plane anticipated for neutron-induced recoils. A particularly strong limit for WIMPs with coherent scattering results from selecting a region of the phonon-light plane corresponding to tungsten recoils, where the best module shows zero events.
A new explicit form for the current response of transition edge sensor microcalorimeters operating with large signals is presented.
In the framework of the large signal analysis, it has also been ...recently shown how the thermal decay time is actually time dependent in presence of electrothermal feedback. As a consequence the combination of such current response with the time dependent thermal response is able to explain the improvement in linearity of the integrated in time signal if compared to the pulse height signal. Moreover, it provides the expected energy linearity, when the extreme electrothermal feedback is applied.
Since the development of the first MgB 2 tapes, ASG Superconductors started an R&D activity aimed to produce magnets using the MgB 2 conductor. Reacted and wound magnesium diboride double pancake ...coils were designed, manufactured (using industrial equipment) and tested, in a cryogen free apparatus, by ASG Superconductors. Each double pancake coil was produced by winding a single length of MgB 2 , 1600 m long, multifilamentary stabilized tape. The successful achievement of the tests allowed us to produce and test the first coil made with 6 single double pancakes, then the second coil and finally the completion of a cryogen free magnet for MRI application. This paper reports the main features of the coil design and construction, the magnet and the test results.
A magnesium diboride cable was assembled by braiding nine strands obtained by a powder-in-tube, in situ, multifilamentary wire. The cable was heat treated at 700 deg C for 20 min together with two ...short samples taken from the same wire. Cable and wires were electrically characterized at several temperatures and applied magnetic fields by measuring the voltage-current characteristics. The critical currents of the cable are in good agreement with the critical current of the wires, showing that no degradation occurred during the cabling procedure.
We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This ...analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c^{2}.
We report on the search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 10 GeV=c2 from the analysis of the entire dataset acquired with a low-radioactivity argon ...target by the DarkSide-50 experiment at Laboratori Nazionali del Gran Sasso. The new analysis benefits from more accurate calibration of the detector response, improved background model, and better determination of systematic uncertainties, allowing us to accurately model the background rate and spectra down to 0.06 keVer. A 90% C.L. exclusion limit for the spin-independent cross section of 3 GeV=c2 mass WIMP on nucleons is set at 6 × 10-43 cm2, about a factor 10 better than the previous DarkSide-50 limit. This analysis extends the exclusion region for spin-independent dark matter interactions below the current experimental constraints in the 1.2, 3.6 GeV=c2 WIMP mass range.
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