Escalation and optimisation of primary breast cancer treatment with antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have become the standard of care for metastatic advanced breast cancers, regardless of tumour subtype. Optimal positioning and treatment sequences are being studied, and many new therapies and combinations are also under development. Research into the application of ADC to early breast cancer is spreading. More than 10 clinical trials are being conducted regarding escalation and de-escalation of systemic treatment. In addition, in the sequence of neoadjuvant and adjuvant therapy, multiple key issues are investigated, such as effective sequences of treatments among ADC, cytotoxic chemotherapy, immunotherapy, and anti-human epidermal growth factor receptor 2 antibody therapy to improve treatment response, prognosis and quality of life (QOL). The postoperative activity of ADC with topoisomerase inhibitors for residual diseases is also being studied in post-neoadjuvant therapy settings. At the same time, many studies have focused on the appropriate timing of surgical therapy and response-guided approach. On the other hand, ADCs can cause serious side effects, although these are infrequent. Therefore, careful management is necessary during both pre-operative and post-operative adjuvant therapy. It is also crucial to focus on developing prognostic and predictive biomarkers to assess efficacy, alongside monitoring markers through translational research and image analysis. This review summarizes the development trends in both neoadjuvant and adjuvant settings, as well as recent data on ADCs for primary breast cancer, while addressing unresolved clinical questions. It discusses the escalation and optimization of treatment for primary breast cancer using ADCs, along with the relevant challenges and perspectives.