Analysis of Exploring Optimized Sequential Treatment Strategies of Antibody-Drug Conjugates (ADCs) in HER2-Low-Expressing Breast Cancer

Breast cancer is one of the most common malignancies in women, posing a significant threat to female health. According to current molecular subtypes, breast cancer is classified into hormone receptor-positive, HER2-positive, and triple-negative breast cancer. However, with the development of novel therapeutic strategies such as antibody-drug conjugates (ADCs), increasing attention has been directed toward HER2-low breast cancer (defined as HER2 immunohistochemistry [IHC] 1+ or 2+/FISH-negative), which accounts for approximately 60%-70% of breast cancer cases. ADCs can exert potential therapeutic effects in HER2-low breast cancer through the "bystander effect" and have been widely adopted in clinical practice. Nevertheless, the optimal sequential treatment strategy for HER2-low patients remains unclear, with a lack of definitive clinical guidelines and limited understanding of resistance mechanisms.

This study aims to investigate the efficacy of different ADC sequential regimens in HER2-low breast cancer patients and explore potential resistance mechanisms. By conducting a retrospective analysis of clinical data from HER2-low patients treated with sequential ADCs, the investigators will evaluate the therapeutic outcomes and safety profiles of various ADC sequencing approaches. Additionally, integrating genomic profiling with routine clinical data, the investigators seek to identify prognostic biomarkers and elucidate resistance pathways. The findings are expected to guide personalized treatment strategies for HER2-low breast cancer patients, ultimately improving clinical outcomes.

Inclusion criteria

• Diagnosed with HER2-low breast cancer, defined as immunohistochemistry (IHC) score of 1+ or IHC score of 2+ with negative in situ hybridization (FISH-negative)
• Received sequential administration of two or more ADCs
• Complete data for patient's character, laboratory and imaging test, treatment and follow-up are available.

Exclusion criteria

• Concomitant with other tumor components at the time of diagnosis;
• Have a history of any other malignant tumors;
• Lack of complete data