Systemic treatment and breast cancer outcomes over time: a systematic review of observational studies

Background: Significant advancements have transformed the clinical management of breast cancer (BC), which has become complex. This review aims to provide an overview of how systemic BC treatment strategies have evolved and affected survival in clinical practice. Methods: Studies were identified through PubMed, EMBASE, and Web of Science from 2011 up to April 2024. Cohort studies comparing treatment strategies and their effects on overall survival (OS), disease-free survival (DFS), and invasive disease-free survival (iDFS) were included. Results: A total of 25 studies, with 74,775 patients, were included. Treatments compared included chemotherapy (76%), endocrine therapies (60%), and anti-HER2 therapies (16%). Among chemotherapies, studies comparing taxanes, anthracyclines, and platinum-based chemotherapy in diverse BC subtypes found that only the latter improved DFS in BRCA1 mutation carriers. Aromatase inhibitors (AIs) plus ovarian function suppression showed better outcomes than selective estrogen receptor modulators. AIs also improved iDFS compared to tamoxifen. Trastuzumab with chemotherapy significantly improved OS in HER2-positive patients compared to chemotherapy alone. Conclusions: This review underscores a notable shift towards the use of combined therapies in BC treatment, which appears to be linked to better survival outcomes. Observational studies offer valuable insights into the variability of survival rates and the growing complexity of treatment strategies. These types of studies should be given thoughtful consideration in future clinical decision-making and in shaping treatment guidelines.