sentence: The addition of trastuzumab , pertuzumab , bevacizumab , or lapatinib to chemotherapy significantly ( P < .05 ) improved objective response rate ( ORR ) , time to failure ( TTF ) , and overall survival ( OS ) in patients with HER2-positive ( HER2(+ ) ) disease .
paragraph: Effectiveness of targeted therapy in patients with previously untreated metastatic breast cancer: a systematic review and meta-analysis. Breast cancer is the most common cancer and the most frequent cause of death in women. Targeted therapies offer a possibility of effective and individualized therapy based on the molecular profile of the tumor. The aim of this systematic review was to evaluate the efficacy and safety of targeted agents added to chemotherapy or endocrine therapy in patients with previously untreated metastatic breast cancer (MBC) depending on their human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status (positive or negative). The systematic literature search was performed in PubMed, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs). Thirteen trials were included. The addition of trastuzumab , pertuzumab , bevacizumab , or lapatinib to chemotherapy significantly ( P < .05 ) improved objective response rate ( ORR ) , time to failure ( TTF ) , and overall survival ( OS ) in patients with HER2-positive ( HER2(+ ) ) disease . trastuzumab or lapatinib combined with endocrine therapy significantly (P < .05) improved ORR, time to progression (TTP), and progression-free survival (PFS) in patients with HER2(+) and HR(+) disease. In patients with HER2-negative (HER2(-)) cancer, bevacizumab or lapatinib added to chemotherapy significantly (P < .05), improved ORR but did not prolong PFS and OS (P > .05). In patients with HER2(-) and HR(-) disease, trastuzumab combined with chemotherapy did not significantly improve (P > .05) ORR or PFS. Targeted therapies also increased the overall risk of adverse events. So far, there is a lack of published results for everolimus and trastuzumab emtansine trials in patients with previously untreated MBC. The addition of targeted therapy to chemotherapy or endocrine therapy using HER2 and HR status significantly improved ORR, PFS, and OS in patients with previously untreated MBC.