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Background: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials., Methods: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC., Results: We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group. We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone. Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001., Conclusions: We confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials., Competing Interests: Declaration of competing interest FM reports personal fees from Roche, Novartis, Pfizer, Seagen, Gilead, Astrazeneca, Lilly, Menarini all outside the submitted work (all the disclosed activities are outside the submitted work). CDA reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Daiichi-Sankyo, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, GILEAD, and Daiichi-Sankyo; travel Grants from Gilead and research support (to the Institution) from Novartis, GILEAD, and Daiichi-Sankyo outside the submitted work (all the disclosed activities are outside the submitted work). RC reports fees for talk or consultation from Novartis, Lilly, MSD, Gilead, Roche, Pfizer, Veracyte, Seagen, Astra Zeneca, Daichii Sankyo, Menarini, Pierre-Fabre (all the disclosed activities are outside the submitted work). EB has received grants or contracts from Astra-Zeneca, Roche and honoraria for lectures from Merck-Sharp & Dome, Astra-Zeneca, Pfizer, Eli-Lilly, Bristol-Myers Squibb, Novartis, Takeda and Roche; he has been member of Data Safety Monitoring Board or Advisory Board of Merck-Sharp & Dome, Pfizer, Novartis, Bristol-Myers Squibb, Astra-Zeneca, and Roche (all the disclosed activities are outside the submitted work). AV reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AndromedaE20, Oncotech; support for attending meetings and/or travel: Pierre Fabre, Lilly, Gilead, Seagen, Novartis, MSD, Menarini (all the disclosed activities are outside the submitted work). LDM reports institutional grants from Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, Astrazeneca, Gilead, Pierre Fabre; consulting fees: Eli Lilly, Gilead, Daiichi Sankyio; payment or honoraria for lectures, presentations, speakers bureaus: Roche, Novartis, Pfizer, Eli Lilly, Astrazeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, Agendia, Stemline; support for attending meetings and/or travel: Roche, Pfizer, Eisai, Daiichi Sankyo, Astrazeneca, Gilead; Participation on a Data Safety Monitoring Board or Advisory Board: Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, Astrazeneca, Agendia, GSK, Seagen, Olema, MSD, Stemline Menarini (all the disclosed activities are outside the submitted work). FM reports consultancy fees from Roche, Novartis, AstraZeneca, Daiichy Sankyo, SeaGen, MSD, Eli Lilly, Pfizer, and Pierre Fabre, and Travel Grants from Roche and Astra Zeneca; from May 15th, 2023, FM is Roche employee (all the disclosed activities are outside the submitted work). VG reports personal fees for advisory board membership for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre; personal fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis, Roche and Zentiva; personal fees for expert testimony for Eli Lilly. All the remaining authors have no conflict of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Endocrine therapy is one of the standard adjuvant treatments to reduce the risk of recurrence and mortality in patients with hormone receptor positive early breast cancer. Despite its proven efficacy, ET side effects, which persist over time even if low grade, may deteriorate quality of life. During follow-up visits, emphasis is generally placed on the risk of disease recurrence, while the topic of ET side effects is commonly neglected and discussed only briefly. This could lead to poor adherence to therapy and early treatment discontinuation, resulting in worse survival outcomes. The aim of this review is to provide an overview of the available evidence on the incidence and reporting of ET-related side effects (including vasomotor symptoms, musculoskeletal disorders and genitourinary syndrome of menopause, as well as fatigue, psychological and ocular disorders, dysmetabolic effects and loss of bone density) and of the pharmacological and non-pharmacological strategies available to mitigate symptom burden., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.G. has served on the advisory boards for AstraZeneca, Daichii Sankyo, Exact Sciences, Lilly, MSD, Novartis, Pfizer, Roche, Seagen; has received travel grants from Roche, Celgene, Pfizer and research funding (to the institution) from Novartis and AstraZeneca. G.A. has receivedhonoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational eventsfrom Roche, Pfizer, Lilly, AstraZeneca, Novartis and Gilead; has received travel grants from Roche, Lilly, AstraZeneca and Gilead; has served on the advisory boards forRoche, Novartis, Lilly, Pfizer, MSD, Dompè, Pierre Fabre, Eisai, Sophos, Epionpharma, Gilead, Seagen, Astra Zeneca and Exact Science. F.M. has received fees for consultant/advisory role for Roche, AstraZeneca, Seagen, Novartis, Daichii Sankyo, MSD and Pierre Fabre; has received fees as speaker from AstraZeneca, Daichii Sankyo, MSD, Novartis, Pfizer and Eli Lilly; from May 15(th) 2023, he’s employed at F Hoffmann La Roche, Basel SW. L.D.M. has received personal fees from Eli Lilly, Novartis, Roche, MSD, Pfizer, Exact Sciences, Pierre Fabre, Daiichi Sankyo, AstraZeneca, Seagen, Eisai, Ipsen and Gilead.M.D.L. reports personal fees from Pfizer, Novartis, Roche, AstraZeneca, Eli Lilly, MSD, Daiichi-Sankyo, GSK, Sanofi, Celtrion, Organon and Seagen.F.P. has received honoraria for speakers’ bureaus, consultancy, advisory board from Amgen, Exact Sciences, Pierre-Fabre, Gilead, Pfizer, Celgene, GSK, Daiichi Sankyo, Ipsen, Seagen, Takeda, Eli Lilly, MSD, Novartis, AstraZeneca, Roche, Eisai, Viatris; research funding from AstraZeneca, Roche, Eisai. The remaining authors declare no competing interests. Funding declaration: this work was supported by the Italian Ministry of Health – Ricerca Corrente., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A novel class of drugs, antibody-drug conjugates (ADCs), are now rapidly emerging as highly effective treatments for solid tumours. ADCs conjugate conventional chemotherapeutics with highly selective targeted monoclonal antibodies. Anti-HER2 therapies selectively target cancer cells expressing human epidermal growth factor receptor 2 (HER2), among them trastuzumab has been the first HER2-targeting monoclonal antibody to achieve successful results that made it the backbone of anti-HER2 therapies. Trastuzumab drug conjugates (T-DCs), use trastuzumab as a selective antibody to lead cytotoxic drugs inside cancer cells. Trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-Dxd) are the two approved T-DCs. T-Dxd along with other five T-DCs represents "second generation ADCs" that has been firstly tested in HER2 positive breast cancer (BC) and then in HER2-low BC and other cancers showing promising results thanks to extraordinary and innovative pharmacokinetic and pharmacodynamic characteristics. The evidence generated so far are establishing them as a completely new class of agents effective in solid cancer treatments but also warrants physicians against unconventional toxicity profiles. The role of T-DCs in HER2-positive BC has been largely reviewed, while in this review, we provided for the first time in literature an overview of trastuzumab drug conjugates (T-DCs) approved and/or in clinical development with a specific focus on their efficacy and safety profile in HER2-low BC and other solid tumours different from BC. We started by analysing T-DCs biological characteristics that underly the differences in T-DCs pharmacodynamics and safety profile, then presented the main evidence on the activity and efficacy of these emerging T-DCs in HER2-low BC and other HER2 overexpressing and/or mutated solid tumours and lastly, we provided an overview of the complex and still evolving scenario in which these compounds should be allocated. A specific focus on possible combination strategies with other drugs such as immunotherapy, chemotherapy and target therapy, to increase T-DCs activity and eventually overcome future upcoming resistance mechanisms, are here also critically reviewed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lipid lateral diffusion in membrane bilayers is a fundamental process exploited by cells to enable complex protein structural and dynamic reorganizations. For its importance, lipid mobility in both cellular and model bilayers has been extensively investigated in recent years, especially through the application of time-resolved, fluorescence-based, optical microscopy techniques. However, one caveat of fluorescence techniques is the need to use dye-labeled variants of the lipid of interest, thus potentially perturbing the structural and dynamic properties of the native species. Generally, the effect of the dye/tracer molecule is implicitly assumed to be negligible. Nevertheless, in view of the widespread use of optically modified lipids for studying lipid bilayer dynamics, it is highly desirable to well assess this point. Here, fluorescence correlation spectroscopy (FCS) and molecular dynamics (MD) simulations have been combined together to uncover subtle structural and dynamic effects in DOPC planar membranes enriched with a standard Rhodamine-labeled lipid. Our findings support a non-neutral role of the dye-labeled lipids in diffusion experiments, quantitatively estimating a decrease in lipid mobility of up to 20% with respect to the unlabeled species. Moreover, results highlight the existing interplay between dye concentration, lipid lateral diffusion and membrane permeability, thus suggesting possible implications for future optical microscopy studies of biophysical processes occurring at the membrane level.

The aim of this study was to compare the results obtained using an electrothermal bipolar vessel sealing system (Ligasure Precise), a harmonic curved shears (Harmonic Focus) and traditional technique in total thyroidectomy. We have enrolled 93 patients and assigned randomly to three groups of 31 pt: groups L (Ligasure Precise), F (Harmonic Focus) and C (traditional thecnique). Recorded data were demographics, preoperative serum calcium levels, operation time, length of hospital stay, weight of exported gland and pathology, postoperative calcemia at one and two days and recurrent laryngeal nerve paralysis. The three groups did not present statistically significant differences in term of age, gender and pathology classification. No postoperative haemorrhages were observed. The overall incidence of hypocalcemia was 38.9% (36 pt) and the mean days of hospitalization were 2.3 days without statistically significant differences between the three groups. Only one patient (group F) presented temporary recurrent laryngeal nerve paralysis. Mean operation time (minutes) was significantly reduced by approximately 15% in group F (62.7+/-14.1) compared with group C (72.7+/-13.6; Kruskal-Wallis test: p<0.05). Both devices resulted safe and efficient. The only advantage observed was a significant reduction operation time when using Harmonic Foscus curved shears compared to the other techniques.