Hotspot issues and considerations in multi-gene testing in breast cancer

Abstract Multigene testing serves as a cornerstone of precision oncology, reshaping the holistic management of breast cancer across its continuum. In early-stage HR-positive/HER2-negative (HR+/HER2-) disease, genomic assays such as MammaPrint ® and Oncotype DX ® enable refined risk stratification; however, their evidence bases diverge significantly when extrapolated to node-positive (1–3 LN+) populations, where only MammaPrint ® currently meets the threshold for guiding chemotherapy de-escalation. For premenopausal patients, age acts as an effect modifier, necessitating the integration of genomic risk with clinical and ovarian function suppression considerations. Beyond adjuvant decisions, these assays also inform extended endocrine therapy duration and anthracycline-sparing strategies, albeit with varying levels of evidence. In advanced disease, dynamic monitoring of resistance driver genes—particularly ESR1 and PIK3CA via circulating tumor DNA (ctDNA)—is critical for overcoming endocrine resistance and tailoring targeted therapies. Notably, ctDNA analysis facilitates the detection of “molecular recurrence” prior to radiological progression, shifting surveillance toward preemptive intervention. Liquid biopsy further provides risk stratification and treatment response evaluation in both early and advanced settings. Despite persistent challenges regarding cross-platform discordance and standardization, multigene testing epitomizes the integration of molecular insights with clinical practice. Ongoing research and health-economic evaluations, particularly within the Chinese healthcare context, promise to refine these strategies toward truly individualized care.