Real-world Data on First-line Systemic Therapy for Hormone Receptor-positive HER2-negative Metastatic Breast Cancer: A Trend Shift in the Era of CDK 4/6 Inhibitors

Hormone receptor-positive (HR⁺) human epidermal growth factor receptor-2 negative (HER2^-) tumors represent the most common subtype of metastatic breast cancer (MBC). International guidelines clearly state that endocrine therapy (ET) should be considered the preferred first-line therapy for these patients in the absence of very symptomatic visceral disease or evidence of endocrine resistance. Nonetheless compliance with guidelines significantly vary worldwide for many different reasons. Historically, a substantial proportion of patients with HR⁺ HER2^- MBC have been treated with chemotherapy (CT) in first-line setting, jeopardizing patients' quality of life without a significant benefit in outcome. In 17 observational studies, including more than 63,000 patients, ET was most frequently used in first-line treatment of HR⁺/HER2^- MBC (range, 42%-87%), nonetheless a high proportion of patients received CT (13%-66%) as initial therapy. More recently, results of clinical trials with CDK 4/6 inhibitors improved response, progression-free and overall survival in this population and are currently the standard of care. There was a trend toward increased use of ET in recent years. This review article aims to evaluate real-world data on patterns of first-line treatment of HR⁺ HER2^- MBC with a special focus on the use of CT in this setting and the potential implications and perceived preliminary changes after the introduction of CDK 4/6 inhibitors.