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Abstract Background Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. Methods Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. Results HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. Conclusion Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.

Background: Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features.Methods: Expression of ObR, HER2, phospho-HER2 was assessed by immunoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data.Results: HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors.Conclusion: Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments. [ABSTRACT FROM AUTHOR]

Objectives: To compare surgical outcomes and sperm retrieval rates (SRRs) between conventional microsurgical-assisted testicular sperm extraction (m-TeSE-Group A) and testicular sperm extraction performed with surgical loupes (l-TeSE-Group B) in adult males with non-obstructive azoospermia (NOA). Methods: A multicentric prospective randomized trial (ethics committee no. 202/2022) in accordance with the CONSORT guidelines was conducted from March 2022 to April 2024. Adult males with NOA without genetic alterations who signed the informed consent were enrolled. SRRs, intra- and postoperative complications (according to the Clavien-Dindo classification), and hormonal profile changes were considered as outcomes during the follow-up period. Results: A total of 42 NOA patients were enrolled. The median age was 35 years (IQR: 33-49). The preoperative median FSH was 16.5 mIU/mL (IQR: 11.6-22.5) and the total testosterone was 4.6 (3.5-5.6). Overall, the SRR was 22.6%, with sperm retrieved from 19 testes. Histopathological findings reported Sertoli cell-only syndrome (SCOS) in 46.4% (39 cases), hypospermatogenesis in 26.2%, and germ cell arrest in 26.2% of the patients. No intraoperative complications were recorded. The postoperative complications were minimal (Clavien-Dindo grade I), but no significant differences were recorded in-between the two surgical approaches. Considering the operative time of the testicular exploration alone, Group B seemed to be faster than the m-TeSE, with a median time saving of 8 min ( p < 0.01). Conclusion: The use of surgical loupes was safe and comparable with m-TeSE in terms of the SRRs and complication rates. L-TeSE offered a reduction in the operative time compared with m-TeSE.

Sildenafil is one of the most used phosphodiesterase type 5 inhibitor (PDE5i) for the treatment of erectile dysfunction (ED) in clinical practice. A new oral suspension formulation (OSF) of sildenafil has been introduced to overcome the drawbacks of previous formulations. We assess the efficacy and patients' experience with sildenafil 50 mg OSF in men with ED who were taking the sildenafil oro-dispersible film (ODF). Demographics and clinical data from 70 consecutive men with mild-moderate ED were analysed. Patients were treated with sildenafil 50 mg ODF for 12 weeks (follow-up 1), then, after 2-week washout, were administered sildenafil 50 mg OSF for 12 weeks (follow-up 2). At each follow-up, patients completed the International Index of Erectile Function (IIEF), the Patient Global Impression of Improvement (PGI-I), and the Psychological and Interpersonal Relationship Scales-Short Form (PAIRS-SF) questionnaires. Descriptive statistics described the whole cohort. The Wilcoxon Signed Rank Test assessed potential differences in psychometric scores at different follow-up assessments. Logistic regression analyses tested the associations between study variables and satisfaction after sildenafil OSF treatment. Overall, median age was 56 (51-62) years, and median IIEF-EF score was 14 (12-17). Compared to baseline, IIEF-EF scores significantly improved after sildenafil ODF and OSF treatment (all p < 0.01) with no differences between the two formulations. IIEF-overall satisfaction (OS) was higher after sildenafil OSF than ODF (p < 0.001). Similarly, median PGI-I score were better after sildenafil OSF than ODF (p < 0.001). The PAIRS-SF spontaneity scores were significantly higher after OSF than ODF (p < 0.01). At multivariable logistic regression analysis, younger age (p = 0.02) and lower baseline IIEF-EF scores (p = 0.01) were independent predictors of improved satisfaction with OSF compared to ODF. The sildenafil OSF and ODF had similar efficacy, however the new OSF provides higher satisfaction and spontaneity scores compared to the oro-dispersible film., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations; all patients signed an informed consent agreeing to share their own anonymous information for other future studies. The study was approved by the Hospital Ethical Committee (Prot. 060182 – SilOros)., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Excess adiposity is associated with several factors involved in carcinogenesis and breast cancer progression. Evidence supporting the role of body composition in breast cancer treatment is promising, but still scanty and mainly focused on adjuvant treatment. The aim of this study was to evaluate the changes in body composition during neoadjuvant chemotherapy and its association with pathologic complete response and survival outcome in patients treated for operable/locally advanced breast cancer., Methods: A retrospective review of patients with breast cancer treated with neoadjuvant chemotherapy was performed in the Oncology Section of the Department of Medicine, University of Verona between 2014 and 2019. Body composition was evaluated from clinically acquired computed tomography scans at diagnosis and after neoadjuvant chemotherapy. Descriptive statistic was adopted. The associations of body composition measures with pathologic complete response and disease-free survival were analyzed. Kaplan-Meier curves were compared with log-rank analysis., Results: Data from 93 patients were collected. After neoadjuvant chemotherapy, the adipose compound changed significantly across all body mass index categories. Body composition parameters had no significant effect on pathologic complete response. Survival analysis showed that a high gain of visceral adipose tissue during neoadjuvant chemotherapy was associated with shorter disease-free survival (hazard ratio, 10.2; P = 0.026). In particular, disease-free survival was significantly worse in patients who gained ≥10% of visceral adipose tissue compared with patients who gained <10% of visceral adipose tissue (5-y disease-free survival 71.4 versus 96.3, P = 0.009, respectively)., Conclusions: Our results indicated that neoadjuvant chemotherapy significantly affects body composition, which seems to have an effect on survival outcome of breast cancer, highlighting the relevance of the body composition assessment when estimating treatment outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are now a backbone of treatment for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. CDK4/6i plus ET is more effective than ET alone in this setting; however, the risk of grade 3-4 adverse events also increases. Approved agents in this class have similar efficacies, but important differences due to their structural and pharmacological properties. We review biomarkers and discuss determinants to inform a rational approach to therapy choice when selecting the most appropriate ET and CDK4/6i partners. We also identify subgroups that may benefit from specific ET-CDK4/6i combinations and discuss strategies to overcome resistance. This personalized approach aims to minimize treatment-related toxicities that may affect patient QoL and compliance, and ultimately therapy efficacy., Competing Interests: Conflict of interest LG reports Consulting or Advisory Role from Eli Lilly and Novartis, outside the submitted work. All other authors declare no potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The impact of the adherence to dietary guidelines of early-stage breast cancer (EBC) patients on body composition changes during treatment is not entirely defined. This study aimed to evaluate the role of an evidence-based nutrition educational intervention, according to adherence to dietary guidelines, in EBC patients., Methods: This prospective study included EBC patients, candidates for neoadjuvant/adjuvant therapy. Patients received an evidence-based tailored nutrition educational intervention. The adherence to dietary guidelines, anthropometric and dietary assessments, and blood glucose and lipid profile tests were evaluated at baseline and after a 12-months nutritional intervention., Results: Two hundred and forty-three patients were enrolled. At baseline, 38.3% and 23.9% of patients were overweight and obese, weight gain ≥5% (compared to 6-months before enrollment) and central obesity were observed in 47.3% and 52.7% of patients, respectively. Adherence to dietary guidelines was low (median Med-Diet score: 6 [IQR 4-8]). After the nutritional intervention (median follow-up: 22 months [range 12-45]), adherence to dietary guidelines significantly increased (median Med-Diet score: 12 [IQR 8-13]), p < 0.0001). High adherence to dietary guidelines (defines as Med-Diet score ≥10) significantly correlated with: 1) overall weight loss ≥5% (21.8% vs. 2.5%, p = 0.003); 2) median BMI drop (from 25.6 kg/m 2 to 24.4 kg/m 2 , p = 0.003); 3) lower prevalence of central obesity (38.2% vs. 7.2%, p = 0.01); 4) improvement in blood glucose levels and lipid profile., Conclusion: This study suggests that an evidence-based tailored nutrition educational intervention during treatment for EBC significantly increases overall adherence to dietary guidelines, and it improves both anthropometric measures and serum metabolic biomarkers in patients with high adherence., Competing Interests: Declaration of competing interest S.P. received honoraria or speakers' fee from Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche. M.M. received speakers' honoraria from and participated on advisory boards for: EUSA Pharma, Pfizer, MSD, AstraZeneca, Merck-Serono and Mylan. E.B. received speakers' and travels' fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche. E.B received consultant's fee from Roche, Pfizer. E.B. received institutional research grants from Astra-Zeneca, Roche. L.C. received honoraria or speakers' fee from Novartis, Istituto Gentili and Eli-Lilly. The other authors declare that they have no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population., Methods: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m 2 (arm A) or 125 mg/m 2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety., Results: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively)., Conclusion: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m 2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease., Trial Registration: EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222 . Retrospectively registered on May 26, 2016.

Background: On February 23rd, the 1st case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22-inpatient bed coronavirus disease (COVID) Unit, and we reshaped our organisation to face the SARS-CoV-2 epidemic, while maintaining oncological activities., Methods: We tracked down (i) volumes of oncological activities (January 1st - March 31st, 2020 versus the same period of 2019), (ii) patients' and caregivers' perception and (iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active"' oncological patients., Results: As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations and specialist visits in January-March 2020 was 8%, 6% and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8 of 85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID Unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active"' oncological disease (2 died of infection-related complications)., Conclusions: A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organisational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum., Competing Interests: Conflict of interest statement M.M. reports receiving personal fees from Pfizer, EUSA Pharma and Astra Zeneca, outside the submitted manuscript. S.P. reports receiving honoraria or speakers' fee from Astra Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche, outside the submitted manuscript. All remaining authors have declared no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Background: There is a heterogeneous literature on healthcare utilization patterns at the end of life. The objective of this study is to examine the impact of closeness to death on the utilization of acute hospital-based healthcare services and some primary healthcare services and compare differences in gender, age groups and major causes of death disease specific mortality., Methods: A matched case-control study, nested in a cohort of 411,812 subjects, linked to administrative databases was conducted. All subjects were residents in the Friuli Venezia Giulia Region (Italy), born before 1946, alive in January 2000 and were followed up to December 2014. Overall, 158,571 decedents/cases were matched by gender and year of birth to one control, alive at least one year after their matched case's death (index-date). Hospital admissions, emergency department visits, drug prescriptions, specialist visits and laboratory tests that occurred 365 days before death/index-date, have been evaluated. Odds Ratios (ORs) for healthcare utilization were estimated through conditional regression models, further adjusted for Charlson Comorbidity Index and stratified by gender, age groups and major causes of death., Results: Decedents were significantly more likely of having at least one hospital admission (OR 7.0, 6.9-7.1), emergency department visit (OR 5.2, 5.1-5.3), drug prescription (OR 2.8, 2.7-2.9), specialist visit (OR 1.4, 1.4-1.4) and laboratory test (OR 2.7, 2.6-2.7) than their matched surviving counterparts. The ORs were generally lower in the oldest age group (95+) than in the youngest (55-74). Healthcare utilization did not vary by sex, but was higher in subjects who died of cancer., Conclusion: Closeness to death appeared to be strongly associated with healthcare utilization in adult/elderly subjects. The risk seems to be greater among younger age groups than older ones, especially for acute based services. Reducing acute healthcare at the EOL represents an important issue to improve the quality of life in proximity to death., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC)., Methods: Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well., Results: Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap., Conclusions: Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Angiogenesis plays a fundamental role in breast cancer (BC) growth, progression and metastatic spread. After the promising introduction of bevacizumab for the treatment of advanced BC, the initial enthusiasm decreased when the FDA withdrew its approval in 2011. Nevertheless, several clinical studies exploring the role of bevacizumab have been subsequently published. Areas covered: The aim of this study is to review the available clinical trials exploring the potential effectiveness of bevacizumab in BC, regardless of the disease setting. Expert opinion: Even if the evidence suggests that bevacizumab must be ruled out from the HER2-positive and adjuvant setting, bevacizumab's benefit remains uncertain in the neoadjuvant setting and in the advanced treatment of HER2-negative patients. In the first setting, the addition of bevacizumab to chemotherapy increased the pathological complete response (pCR) rate in most clinical trials. However, the current absence of evidence that pCR is a trial-level surrogate for survival requires waiting for long-term results. In the advanced setting, all trials showed a benefit in progression-free survival, but not in overall survival, highlighting an increase of adverse events. The lack of predictors of response represents the main unmet need in which future clinical research will undoubtedly invest.

Tumor spread from primary cardiac sarcoma to the bone is very rare and has a poor prognosis. Only six cases have been reported in the literature. We present a 32-year-old female patient with bone metastases from primary cardiac sarcoma.