Molecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies.

Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of and mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA).

Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study.

Purpose: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm).

Methods: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

Purpose: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months.

Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy.

Purpose: Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known.

Experimental Design: This is a pooled analysis of two studies where patients with stage I (T>1 cm)-III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC.

Safety profile of trastuzumab deruxtecan in advanced breast cancer: Expert opinion on adverse event management.

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that targets human epidermal growth factor receptor 2 (HER2) and has shown promising results in the treatment of advanced/metastatic breast cancer. The objective of this report is to provide guidance on the prophylaxis, monitoring, and management of adverse events (AEs) in patients with breast cancer treated with T-DXd, and to emphasize that proper management of AEs is needed to optimize the effectiveness of T-DXd treatment and reduce the number of discontinuations. The article covers various aspects of T-DXd treatment, including its clinical efficacy, safety profile, and dosing considerations, and provides practical recommendations for managing AEs, such as nausea/vomiting, interstitial lung disease, and hematologic toxicity.

Patient-reported outcomes in high-risk HR+ /HER2- early breast cancer patients treated with endocrine therapy with or without palbociclib within the randomized PENELOPE study.

Background: The PENELOPE trial investigating efficacy and safety of additional 1-year post-neoadjuvant palbociclib to standard endocrine therapy (ET) high-risk hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer patients failed to improve invasive disease-free survival (iDFS). This analysis compared patient-reported outcomes (PROs) between treatment groups.

Patients And Methods: Patients received 13 cycles of palbociclib 125 mg/day (n = 631) or placebo (n = 619) orally for 3 out of 4 weeks + ET.

Correlation between breast cancer subtypes determined by immunohistochemistry and n-COUNTER PAM50 assay: a real-world study.

Purpose: Molecular subtyping based on gene expression profiling (i.e., PAM50 assay) aids in determining the prognosis and treatment of breast cancer (BC), particularly in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, where luminal A and B subtypes have different prognoses and treatments.

Clinical Experience with Abemaciclib in Patients Previously Treated with Another CDK 4/6 Inhibitor in a Tertiary Hospital: A Case Series Study.

The three approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including abemaciclib, have shown differences in their preclinical, pharmacological, and clinical data. Abemaciclib stands out for its broader target range and more rapid and intense activity. It has demonstrated efficacy as a monotherapy or in combination with tamoxifen in endocrine-refractory metastatic breast cancer (MBC) patients with prior chemotherapy.

Real-World Use of Highly Sensitive Liquid Biopsy Monitoring in Metastatic Breast Cancer Patients Treated with Endocrine Agents after Exposure to Aromatase Inhibitors.

Endocrine-resistant, hormone receptor-positive, and HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) is largely governed by acquired mutations in the estrogen receptor, which promote ligand-independent activation, and by truncal alterations in the PI3K signaling pathway, with a broader range of gene alterations occurring with less prevalence. Circulating tumor DNA (ctDNA)-based technologies are progressively permeating the clinical setting. However, their utility for serial monitoring has been hindered by their significant costs, inter-technique variability, and real-world patient heterogeneity.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease.

Background: Xentuzumab is a humanised monoclonal antibody that binds to IGF-1 and IGF-2, neutralising their proliferative activity and restoring inhibition of AKT by everolimus. This study evaluated the addition of xentuzumab to everolimus and exemestane in patients with advanced breast cancer with non-visceral disease.

Methods: This double-blind, randomised, Phase II study was undertaken in female patients with hormone-receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer with non-visceral disease who had received prior endocrine therapy with or without CDK4/6 inhibitors.

SEOM-GEICAM-SOLTI clinical guidelines in advanced breast cancer (2022).

Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer.