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Background: Cardiovascular (CV) comorbidities and concurrent medications with risk of heart rate-corrected QT interval (QTc) prolongation can impact treatment decisions and safety discussions for patients with breast cancer. However, limited data are available regarding their prevalence in patients with HR + /HER2- metastatic breast cancer (mBC). We evaluated the prevalence of CV comorbidities, the use of concurrent medications with risk of QTc prolongation, and treatment patterns in patients with newly diagnosed HR + /HER2 - mBC.

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Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses.

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: Early-onset breast cancer (EOBC), particularly in patients under 40, presents with distinct biological characteristics and worse survival outcomes compared to late-onset cases. Despite intensive treatments, EOBC patients, especially those with hormone receptor-positive, HER2-negative (HR+/HER2-) subtypes, show poorer prognosis. CDK4/6 inhibitors, combined with endocrine therapy (ET) have become the standard for HR+/HER2- metastatic breast cancer, yet younger patients are underrepresented in clinical trials.

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Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown.

Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel-Haenszel method for adverse events (AEs) with Review-Manager version-5.

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Introduction: CDK4/6 inhibitors in combination with aromatase inhibitors (AIs) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer. Landmark trials have demonstrated a comparable progression-free survival (PFS) across CDK4/6 inhibitors, but the overall survival (OS) outcomes have varied. This study aimed to evaluate the real-world PFS and OS for palbociclib and ribociclib when combined with AIs in patients with HR+/HER2- advanced breast cancer.

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