Biomedical subjects

Fabio Puglisi

Publications and source records attributed to Fabio Puglisi.

3 recordsLinked to original sources

PubMed2026

Associations of neighborhood deprivation with breast cancer tumor genomics, targeted treatment use, and survival.

PURPOSE: Neighborhood environments appear to influence breast cancer biology and outcomes. This study evaluated somatic, treatment, and outcome differences by Area Deprivation Index in patients with metastatic breast cancer. METHODS: Retrospective, population-based cohort study using clinical and genomic data gathered between 2015 and 2024 at four academic institutions in the United States. The outcomes were differences in circulating tumor DNA mutation profiles, PI3K inhibitor use, and survival between patients with metastatic breast cancer living in high deprivation (Area Deprivation Index ≥ 60 by national rank) and low deprivation (< 60) neighborhoods. RESULTS: Among 1127 patients with metastatic breast cancer, 335 (29.7%) lived in high deprivation areas. These patients were more likely to have TP53 mutations (Odds ratio 1.49, 95% Confidence Interval 1.07-2.08, P = 0.018). Among hormone receptor-positive, HER2-negative patients eligible for PI3K inhibitors, those from high deprivation areas were less likely to receive them (17.4% vs. 36.7%, p = 0.02). Median survival from the time of circulating tumor DNA testing was significantly shorter in the high deprivation group (24 months versus 28 months, p = 0.04) and for Black patients in the high deprivation group versus Black patients in low deprivation group and all White patients (15 months versus 25-28 months, p = 0.02). CONCLUSIONS: We found that patients with metastatic breast cancer living in high deprivation neighborhoods were more likely to have TP53 mutations, an indicator of aggressive disease biology, less likely to receive PI3K inhibitors, and had shorter overall survival compared to patients living in low deprivation neighborhoods by Area Deprivation Index.

Humans↗

PubMed2026

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of ≥ 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer↗

PubMed2026

Prognostic and predictive value of HRD in early triple negative breast cancer (TNBC).

This review explores the emerging role of homologous recombination deficiency (HRD) as both a prognostic and predictive biomarker in early-stage triple-negative breast cancer (TNBC). HRD arises from the defective repair of DNA double-strand breaks through homologous recombination, resulting in genomic instability and increased sensitivity to DNA-damaging agents such as platinum compounds. The review outlines the biological basis of HRD, including genomic signatures such as loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and highlights its prevalence in TNBC compared with other breast cancer subtypes. Clinical trials have shown that HRD-positive patients often achieve higher pathological complete response rates and improved disease-free survival when treated with chemotherapy. However, conflicting evidence across trials underscores the need for more reliable and standardized methods for HRD assessment. The review also explores the therapeutic potential of poly(ADP-ribose) polymerase inhibitors in TNBC, particularly in BRCA-mutated or HRD-positive tumors. Agents such as olaparib, talazoparib, and niraparib have demonstrated promising efficacy in both neoadjuvant and adjuvant settings with some trials suggesting that selected patients may avoid chemotherapy. Furthermore, HRD-positive tumors are characterized by increased genomic instability and a higher neoantigen burden, promoting immune cell infiltration, particularly of tumor-infiltrating lymphocytes, which may enhance responsiveness to immune checkpoint inhibitors. Overall, current evidence supports the role of HRD as a promising biomarker in TNBC. However, further research is required to refine its clinical utility and to integrate HRD testing into personalized treatment strategies, especially in combination with emerging therapies such as immunotherapy.

Humans↗