Inter-Assay Variability of TROP2 Immunohistochemistry in Triple-Negative Breast Cancer.

Background And Objective: Sacituzumab govitecan, an anti-trophoblast cell surface antigen 2 (TROP2) antibody-drug conjugate, has been approved by both the US Food and Drug Administration and European Medicines Agency for patients with metastatic triple-negative breast cancer who have received two or more prior systemic therapies, including at least one of them for advanced disease. Although TROP2 evaluation is not required for patient selection, survival data from the ASCENT trial show improved response rates in patients with high TROP2 expression by immunohistochemistry. However, there is no standardized testing assay for these patients.

Artificial intelligence as treatment support in breast cancer: current perspectives.

With the increasing amount of information related to breast cancer (BC) management, artificial intelligence (AI) has emerged as a tool with the potential to enhance the quality of treatment through the efficient integration of large datasets; however, the specific areas for which AI may be ready for clinical implementation remain unclear. In this narrative review, we recapitulate the available data on AI utilization in BC treatment by focusing on surgical therapy, radiation therapy, systemic and supportive treatment, but including the diagnostics, too. While AI has been implemented successfully in mammography screening, preoperative consultation, and radiation oncology, its use intraoperatively, post-operatively, and in systemic and supportive treatment is still in development.

Risk of Severe Outcomes From COVID-19 in Immunocompromised People During the Omicron Era: A Systematic Review and Meta-Analysis.

Purpose: COVID-19 imposes a high burden on people with immunocompromising/immunosuppressive (IC/IS) conditions. This is the first large-scale, comprehensive meta-analysis encompassing major IC/IS categories to assess the risks of severe outcomes from COVID-19 in people with IC/IS conditions during the Omicron era-the period dominated by the most recent major COVID-19 variant.

Methods: A systematic search of Embase, MEDLINE, PubMed, Europe PMC, Latin American and Caribbean Health Sciences Literature, Cochrane COVID-19 Study Register, and WHO COVID-19 database was performed to identify studies published between January 1, 2022, and March 13, 2024.

Positioning oral selective estrogen receptor degraders in patients with metastatic breast cancer.

Approximately 40 % of patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (mBC) who receive first-line treatment with CDK4/6 inhibitors (CDK4/6i) and aromatase inhibitors (AIs) develop acquired ESR1 mutations, leading to ligand-independent ER activation and resistance to AIs. Fulvestrant, the first selective estrogen receptor degrader (SERD) approved for clinical use, was developed to address this resistance and has remained the standard second-line endocrine therapy. However, its clinical use is limited by intramuscular administration and low bioavailability.

Immunotherapy in rare histologies of breast cancer: challenges, opportunities, and future perspectives.

Purpose Of Review: Immunotherapy has transformed the management of several malignancies, yet its role in rare breast cancer histologies remains poorly defined due to limited research and few dedicated clinical trials. This review critically assesses current knowledge and emerging opportunities for immunotherapy in these uncommon breast cancer subtypes.

Recent Findings: Rare breast cancer histologies exhibit heterogeneous immunogenicity, including variable expression of programmed death-ligand 1 (PD-L1), differing levels of tumor-infiltrating lymphocytes (TILs), and distinct mutational burdens.

The Impact of Concordance Between Liquid and Tissue Biopsy for Actionable Mutations: Insights from the Rome Trial.

Purpose: This analysis evaluated the influence of tissue and liquid biopsy concordance on outcomes in patients enrolled in the ROME Trial.

Experimental Design: The ROME trial, a phase II multicenter study, enrolled 1,794 patients with advanced solid tumors. Next-generation sequencing (NGS) was performed on tissue and liquid biopsies using FoundationOne CDx and FoundationOne Liquid CDx, A centralized Molecular Tumor Board (MTB) reviewed results to identify actionable alterations, with 400 patients randomized to tailored therapy (TT) or standard-of-care (SoC).

An Interdisciplinary Ecosystem for the Prevention of Cardiotoxicity in Older Patients With Breast Cancer: Protocol for a Prospective and Multicentric Study.

Background: Over 50% of newly diagnosed patients with breast cancer are aged ≥65 years. Due to age-related factors and the presence of comorbidities, these patients are particularly vulnerable to developing cardiac toxicity associated with cancer treatments, which may lead to suboptimal interventions and undertreatment, resulting in poorer health outcomes, quality of life (QoL) deterioration, and increased health care costs. Given the underrepresentation of older patients with breast cancer in clinical trials and the increasing recognition of the impact of psychosocial and behavioral factors on cardiovascular disease onset, broader and interdisciplinary studies are required to develop new and innovative best practices for this clinical population.

Comparative efficacy between real-world and randomized studies of palbociclib+endocrine therapy in HR-positive/HER2-negative metastatic breast cancer: systematic review and meta-analysis.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations.

Artificial intelligence in breast cancer radiotherapy: Insights from the Toolbox Consortium Delphi study.

Artificial intelligence (AI) is being incorporated in several breast cancer care domains, including for radiation therapy (RT). Herein we provide a review about AI for the management and planning of RT for breast cancer, which is part of the Toolbox-3 project's multidisciplinary Delphi study, including a literature review of studies related to the topic raised by the Delphi questionnaire. Our review shows that available evidence mainly consists of small single institutional studies, often at least partly supported by commercial companies.

Management of MET-Driven Resistance to Osimertinib in -Mutant Non-Small Cell Lung Cancer.

Epidermal growth factor receptor () mutations occur in approximately 10-20% of Caucasian and up to 50% of Asian patients with oncogene-addicted non-small cell lung cancer (NSCLC). Most frequently, alterations include exon 19 deletions and exon 21 L858R mutations, which confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). In the last decade, the third-generation EGFR-TKI osimertinib has represented the first-line standard of care for EGFR-mutant NSCLC.

Integrating tissue and liquid biopsy comprehensive genomic profiling to predict efficacy of anti-EGFR therapies in metastatic colorectal cancer: Findings from the CAPRI-2 GOIM study.

Introduction: We investigated the role of integrating tissue biopsy (TBx)- and liquid biopsy (LBx)-comprehensive genomic profiling (CGP) to predict the activity of FOLFIRI plus cetuximab.

Methods: The CAPRI-2 GOIM study is a non-randomized phase 2 study evaluating a biomarker-driven anti-EGFR treatment in three lines of therapy in patients with RAS/BRAF wild type metastatic colorectal cancer. At baseline, TBx and LBx were analyzed using the FoundationOne CDx platform.

Advancing equitable access to innovation in breast cancer.

This manuscript critically examines the challenges associated with the design and conduct of academic global breast cancer trials outside the influence of pharmaceutical companies, leveraging insights from the Breast International Group (BIG). In the past 4 decades significant declines in breast cancer mortality have occurred, partly related to industry-academic clinical and translational partnerships with long term study follow up. However, in the past decade these partnerships have largely uncoupled.

Biomarker testing implementation for molecularly targeted therapy in non-small cell lung cancer patients.

Background: Recent advancements in identifying druggable molecular drivers in lung adenocarcinoma (LUAD), have transformed treatment paradigms. In recent years, Next Generation Sequencing (NGS) has gained momentum as an essential tool for in-depth simultaneous analysis of multiple genes, thereby streamlining the diagnostic process in LUAD. Despite this, the implementation of NGS testing in both the US and Europe remains suboptimal.

Circulating tumor DNA: a biomarker for oncology drug development in phase I clinical trials?

Introduction: Circulating tumor DNA (ctDNA) is a noninvasive and promising biomarker for cancer diagnosis, prognosis, and therapeutic monitoring, offering significant potential for real-time insights into tumor dynamics when compared to traditional tissue-based biopsies. Phase I oncology clinical trials, which primarily focus on assessing the safety, pharmacodynamics, and early activity of novel cancer therapies, might find in the unique biological characteristics of ctDNA, a valuable biomarker to boost the efficiency of testing novel agents.

Areas Covered: This review explores the utility of ctDNA as a biomarker in phase I trials, discussing its biological and technical features, clinical relevance, current limitations, and future potential in advancing early clinical drug development.

Overcoming Resistance to CDK4/6 inhibitors in Hormone Receptor positive, HER2 negative breast cancer: Innovative Combinations and Emerging Strategies.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However, approximately 20% of these tumors exhibit intrinsic resistance to such therapies, and most develop acquired resistance mechanisms that drive progression. Biomarker analyses of biological samples from patients treated with CDK4/6i plus ET have identified potential targets for therapeutic combinations.

Tearing down inequalities in the healthcare system across Europe: the BEACON project.

Equity in healthcare remains a pressing issue in cancer care across the European Union. Although numerous European initiatives address prevention, early diagnosis, and treatment, significant disparities in access to innovative cancer therapies persist. Time-to-reimbursement for new anticancer drugs varies widely between member states, depending on national health policies, economic capacity, and healthcare infrastructure.

The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report.

Background: The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new "grey areas" not covered by international guidelines, where treatment decision making is particularly challenging.

Methods: Sixteen relevant statements regarding the management of HR+ /HER2- mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements.

Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors.

A comparative analysis of Denosumab (DMAB) and Zoledronic Acid (ZA) was conducted in a real-world cohort of 864 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with bone metastases, who were undergoing CDK4/6 inhibitors plus endocrine therapy. We evaluated the time to first skeletal-related events (SREs), progression-free survival (PFS), and overall survival (OS). To adjust for confounding variables, we utilized propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methodologies.

Advancing breast cancer therapy in the era of molecular diagnostics.

Advances in cancer biology and drug development now enable treatments tailored to individual tumor profile. Targeting specific molecular alterations marked a significant step forward in cancer care, including breast cancer. Access to these therapies is improving thanks to the implementation of molecular tumor boards and efforts to provide molecular diagnostics at sustainable costs for all.

APOBEC3 mutagenesis drives therapy resistance in breast cancer.

Acquired genetic alterations drive resistance to endocrine and targeted therapies in metastatic breast cancer; however, the underlying processes engendering these alterations are largely uncharacterized. To identify the underlying mutational processes, we utilized a clinically annotated cohort of 3,880 patient samples with tumor-normal sequencing. Mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were prevalent and enriched in post-treatment hormone receptor-positive cancers.

ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy.

Mutations in ESR1 play a critical role in resistance to endocrine therapy (ET) in hormone receptor-positive (HR +)/HER2- metastatic breast cancer (MBC). Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. While most studies have utilized liquid biopsy (LB) for mutation detection, the role of formalin-fixed paraffin-embedded (FFPE) tissue biopsy in this context remains unclear.

Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment.

Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2-positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood.