Metabolic syndrome and early stage breast cancer outcome: results from a prospective observational study.

PURPOSE: Obesity and insulin resistance have been associated with poor prognosis in breast cancer (BC). The present prospective study aimed to investigate the impact of metabolic syndrome (MetS) and its components on early BC (eBC) patients' outcome. METHODS: MetS was defined by the presence of 3 to 5 of the following components: waist circumference > 88 cm, blood pressure ≥ 130/≥ 85 mmHg, serum levels of triglycerides ≥ 150 mg/dL, high density lipoprotein < 50 mg/dL and fasting glucose ≥ 110 mg/dL. Seven hundred and seventeen patients with data on ≥ 4 MetS components at BC diagnosis were enrolled. Study population was divided into two groups: patients with < 3 (non-MetS) vs. ≥ 3 components (MetS). Categorical variables were analyzed by Chi-square test and survival data by log-rank test and Cox proportional hazards regression model. RESULTS: Overall, 544 (75.9%) and 173 (24.1%) women were categorized as non-MetS and MetS, respectively. MetS patients were more likely to be older, postmenopausal, and insulin-resistant compared to non-MetS patients (p < 0.05). In multivariate analysis, MetS patients had a numerically higher risk of relapse [disease-free survival (DFS), hazard ratio (HR) 1.51, p = 0.07] and a significantly higher risk of death compared to non-MetS patients [overall survival (OS), HR 3.01, p < 0.0001; breast cancer-specific survival (BCSS), HR 3.16, p = 0.001]. Additionally, patients with 1 to 2 components of MetS had an increased risk of dying compared to patients with 0 components (OS, HR 4.90, p = 0.01; BCSS, HR 6.07, p = 0.02). CONCLUSIONS: MetS correlated with poor outcome in eBC patients. Among patients without full criteria for MetS diagnosis, the presence of 1 or 2 components of the syndrome may predict for worse survival.

Pregnancy and Breast Cancer: A Challenge for the Multidisciplinary Team. A Single Center Experience and Narrative Review.

Purpose: The diagnosis of breast cancer during pregnancy is a rare event, but it is more frequent in our daily clinical practice due to the progressing aging of pregnant women. The management of a woman affected by pregnancy-associated breast cancer (PABC) remains a challenge for the clinician as it is related to ethical and psychological decisions. Patients and Methods: Here, we retrospectively described 10 cases of PABC in women treated at our Institution. All cases were discussed in the multidisciplinary team. We reviewed available literature data on the topic. Results: Nine out 10 patients were diagnosed with localized breast cancer. The remaining patients were presented with metastatic de novo disease. Median age was 37.5 years (range 26-42). Seven patients presented with grade 3 tumor and 9 patients had Ki-67 value higher than 30%. All but 2 patients received neoadjuvant chemotherapy consisting of sequential anthracyclines and cyclophosphamide followed by weekly paclitaxel during pregnancy. No safety concerns or complications during delivery for both the mothers and the babies were reported. Conclusion: Breast cancer during pregnancy is a challenging clinical situation and all the decisions need to consider both the patients and the fetus safety. Data from our series and from literature confirm the safety of standard chemotherapy approach starting from the second trimester of gestation. More research and effort are needed to offer these patients excellent outcomes and it is mandatory that cases should be closely followed up by a multidisciplinary team.

Treatments for relapsed, BRCA-wild type, platinum-sensitive ovarian cancer: A systematic review and network meta-analysis.

INTRODUCTION: Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment for these patients. We compared the effectiveness of modern and older therapies in relapsed platinum-sensitive, BRCA-wild type, and ovarian cancers using a network meta-analysis (NMA). METHODS: A systematic search of PubMed, EMBASE, and Cochrane Library was performed up to October 31, 2022. Randomized controlled trials (RCT) that compared different second-line approaches were included. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). RESULTS: In total, 17 RCTs (n = 9405) comparing various strategies were included. The risk of death was significantly decreased with carboplatin + pegylated liposomal doxorubicin + bevacizumab compared to platinum-based doublet CT (hazard ratio [HR] = 0.59, 95%CI 0.35, 1). Various strategies, including secondary cytoreduction followed by platinum-based CT, carboplatin + pegylated liposomal doxorubicin + bevacizumab, and platinum-based CT with bevacizumab or cediranib, were better than platinum-based doublets alone for PFS. CONCLUSIONS: This NMA showed that carboplatin + pegylated liposomal doxorubicin + bevacizumab seems to increase the efficacy of standard second-line CT. These strategies can be considered when treating patients with relapsed platinum-sensitive ovarian cancer without BRCA mutations. This study provides systematic comparative evidence for the efficacy of different second-line therapies for relapsed ovarian cancer.

The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis.

INTRODUCTION: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC. METHODS: We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS. RESULTS: The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years. CONCLUSION: This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.