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(1) Background: We estimated the prevalence and clinical outcomes of sarcopenia among breast cancer patients. (2) Methods: A systematic literature search was carried out for the period between July 2023 and October 2023. Studies with breast cancer patients evaluated for sarcopenia in relation to overall survival (OS), progression-free survival (PFS), relapse of disease (DFS), pathological complete response (pCR), or toxicity to chemotherapy were included. (3) Results: Out of 359 screened studies, 16 were eligible for meta-analysis, including 6130 patients, of whom 5284 with non-MBC. Sarcopenia was evaluated with the computed tomography (CT) scan skeletal muscle index and, in two studies, with the dual-energy x-ray absorptiometry (DEXA) appendicular lean mass index. Using different classifications and cut-off points, overall, there were 2007 sarcopenic patients (33%), of whom 1901 (95%) presented with non-MBC. Sarcopenia was associated with a 33% and 29% higher risk of mortality and progression/relapse of disease, respectively. Sarcopenic patients were more likely to develop grade 3–4 toxicity (OR 3.58, 95% CI 2.11–6.06, p < 0.0001). In the neoadjuvant setting, a higher rate of pCR was observed among sarcopenic patients (49%) (OR 2.74, 95% CI 0.92–8.22). (4) Conclusions: Our meta-analysis confirms the correlation between sarcopenia and negative outcomes, especially in terms of higher toxicity.

Background: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug–drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy. Methods: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23). The association between the Drug-PIN continuous score or the Drug-PIN traffic light and the occurrence of treatment-related toxicities and oncological outcomes was evaluated. Results: In total, 177 patients with advanced BRAF-mutated melanoma undergoing BRAF/MEK targeted therapy were included. All grade toxicity was registered in 79% of patients. Cardiovascular toxicities occurred in 31 patients (17.5%). Further, 94 (55.9%) patients had comorbidities requiring specific pharmacological treatments. The median Drug-PIN score significantly increased when the target combination was added to the patient’s home therapy (p-value < 0.0001). Cardiovascular toxicity was significantly associated with the Drug-PIN score (p-value = 0.048). The Drug-PIN traffic light (p = 0.00821) and the Drug-PIN score (p = 0.0291) were seen to be significant predictors of cardiotoxicity. Patients with low-grade vs. high-grade interactions showed a better prognosis regarding overall survival (OS) (p = 0.0045) and progression-free survival (PFS) (p = 0.012). The survival analysis of the subgroup of patients with cardiological toxicity demonstrated that patients with low-grade vs. high-grade DDIs had better outcomes in terms of OS (p = 0.0012) and a trend toward significance in PFS (p = 0.068). Conclusions: DDIs emerged as a critical issue for the risk of treatment-related cardiovascular toxicity. Our findings support the utility of DDI assessment in melanoma patients treated with BRAF/MEK inhibitors.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department’s database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793–63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182–16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464–138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661–31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors.

The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies.

Background: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). Methods: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG. Results: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups (n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p < 0.0001). Conclusions: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.

The actual role of chemotherapy in vulvar cancer is undeniably a niche topic. The low incidence of the disease limits the feasibility of randomized trials. Decision making is thus oriented by clinical and pathological features, whose relevance is generally weighted against evidence from observational studies and clinical practice. The therapeutic management of vulvar cancer is increasingly codified and refined at an individual patient level. It is of note that the attitude towards evidence sharing and discussion within a multidisciplinary frame is progressively consolidating. Viable options included in the therapeutic armamentarium available for vulvar cancer patients are frequently an adaption from standards used for cervical or anal carcinoma. Chemotherapy is more frequently combined with radiotherapy as neo-/adjuvant or definitive treatment. Drugs commonly used are platinum derivative, 5-fluorouracil and mitomicin C, mostly in combination with radiotherapy for radiosensitization. Exclusive chemotherapy in the neo-/adjuvant setting comprises platinum-derivative, combined with bleomicin and methotrexate, 5-fluorouracil, ifosfamide or taxanes. In advanced disease, current regimens include cisplatin-based chemoradiation, with or without 5-fluorouracil, or doublets with platinum in combination with a taxane. Our work is also enriched by a concise excursus on the biologic pathways underlying vulvar cancer. Introductory hints are also provided on targeted agents, a rapidly evolving research field.

The pathologic definition of triple negative breast cancer (TNBC) relies on the absence of expression of estrogen, progesterone and HER2 receptors. However, this BC subgroup is distinguished by a wide biological, molecular and clinical heterogeneity. Among the intrinsic TNBC subtypes, the mesenchymal type is defined by the expression of genes involved in the epithelial to mesenchymal transition, stromal interaction and cell motility. Moreover, it shows a high expression of genes involved in proliferation and an immune-suppressive microenvironment. Several molecular alterations along different pathways activated during carcinogenesis and tumor progression have been outlined and could be involved in immune evasion mechanisms. Furthermore, reverting epithelial to mesenchymal transition process could lead to the overcoming of immune-resistance. This paper reviews the current knowledge regarding the mesenchymal TNBC subtype and its response to conventional therapeutic strategies, as well as to some promising molecular target agents and immunotherapy. The final goal is a tailored combination of cytotoxic drugs, target agents and immunotherapy in order to restore immunocompetence in mesenchymal breast cancer patients.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2−, ABC.

Chemotherapy based on the sequential use of anthracyclines and taxanes has long represented the most efficacious approach in the management of early-stage, triple-negative breast cancer, whose aggressive behavior is widely renowned. This standard chemotherapy backbone was subsequently enriched by the use of carboplatin, based on its association with increased pathologic complete response and efficacy in the metastatic setting. Following the results from the IMpassion130 trial, the recent approval of the immunotherapic agent atezolizumab in combination with chemotherapy as first-line treatment for programmed-death ligand 1-positive, unresectable locally advanced, or metastatic triple-negative breast cancer increasingly fueled the flourishing of trials of immune-checkpoint inhibitors in the early setting. In this work, we review the most recent inherent literature in light of key methodological issues and provide a quantitative summary of the results from phase II–III randomized trials of immunotherapic agents combined with chemotherapy in the setting of interest. Hints regarding future directions are also discussed.

With the introduction of immune checkpoint inhibitors (ICIs) and next-generation vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFR–TKIs), the survival of patients with advanced renal cell carcinoma (RCC) has improved remarkably. However, not all patients have benefited from treatments, and to date, there are still no validated biomarkers that can be included in the therapeutic algorithm. Thus, the identification of predictive biomarkers is necessary to increase the number of responsive patients and to understand the underlying immunity. The clinical outcome of RCC patients is, in fact, associated with immune response. In this exploratory pilot study, we assessed the immune effect of TKI therapy in order to evaluate the immune status of metastatic renal cell carcinoma (mRCC) patients so that we could define a combination of immunological biomarkers relevant to improving patient outcomes. We profiled the circulating levels in 20 mRCC patients of exhausted/activated/regulatory T cell subsets through flow cytometry and of 14 immune checkpoint-related proteins and 20 inflammation cytokines/chemokines using multiplex Luminex assay, both at baseline and during TKI therapy. We identified the CD3+CD8+CD137+ and CD3+CD137+PD1+ T cell populations, as well as seven soluble immune molecules (i.e., IFNγ, sPDL2, sHVEM, sPD1, sGITR, sPDL1, and sCTLA4) associated with the clinical responses of mRCC patients, either modulated by TKI therapy or not. These results suggest an immunological profile of mRCC patients, which will help to improve clinical decision-making for RCC patients in terms of the best combination of strategies, as well as the optimal timing and therapeutic sequence.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast cancer (TNBC). Tumor infiltrating lymphocytes (TILs), Programmed Death-Ligand 1 (PD-L1), and Cluster of Differentiation 73 (CD73) are immune-related biomarkers that can be evaluated in the tumor microenvironment. We investigated if the contemporary expression of these biomarkers combined in a tissue immune profile (TIP) can predict pCR better than single biomarkers in TNBC. Tumor infiltrating lymphocytes (TILs), CD73 expression by cancer cells (CC), and PD-L1 expression by immune cells (IC) were evaluated on pre-NACT biopsies. We defined TIP positive (TIP+) as the simultaneous presence of TILS ≥ 50%, PD-L1 ≥ 1%, and CD73 ≤ 40%. To consider the effects of all significant variables on the pCR, multivariate analysis was performed. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used for model selection. We retrospectively analyzed 60 biopsies from patients with TNBC who received standard NACT. Pathological complete response was achieved in 23 patients (38.0%). Twelve (20.0%) cases resulted to be TIP+. The pCR rate was significantly different between TIP+ (91.7%) and TIP− (25.0%) (p < 0.0001). Using a multivariate analysis, TIP was confirmed as an independent predictive factor of pCR (OR 49.7 (6.30–392.4), p < 0.0001). Finally, we compared the efficacy of TIP versus each single biomarker in predicting pCR by AIC and BIC. The combined immune profile is more accurate in predicting pCR (AIC 68.3; BIC 74.5) as compared to single biomarkers. The association between TIP+ and pCR can be proposed as a novel link between immune background and response to chemotherapy in TNBC, highlighting the need to consider an immunological patients’ profile rather than single biomarkers.

Breast cancer is one of the major causes of cancer-related morbidity and mortality in women worldwide. During the past three decades, several improvements in the adjuvant treatment of hormone receptor-positive/HER2-negative breast cancer have been achieved with the introduction of optimized adjuvant chemotherapy and endocrine treatment. However, estimating the risk of relapse of breast cancer on an individual basis is still challenging. The IRIDE (hIGh Risk DEfinition in breast cancer) working group was established with the aim of reviewing evidence from the literature to synthesize the current relevant features that predict hormone-positive/HER2-negative early breast cancer relapse. A panel of experts in breast cancer was involved in identifying clinical, pathological, morphological, and genetic factors. A RAND consensus method was used to define the relevance of each risk factor. Among the 21 features included, 12 were considered relevant risk factors for relapse. For each of these, we provided a consensus statement and relevant comments on the supporting scientific evidence. This work may guide clinicians in the practical management of hormone-positive/HER2-negative early breast cancers.