Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

SIMPLE SUMMARY: The development of adjuvant and neoadjuvant therapies, and breast cancer surgery for primary breast cancer has led to the dramatic improvements in the survival rates of breast cancer patients over the past 50 years. However, recurrence with distant metastasis during the 10 years after surgical treatment is still seen, although not often. Current clinical perspectives are summarized to address unsolved issues in (neo)adjuvant therapy for primary breast cancer. It is necessary to elucidate the gain of antitumor immunity via anticancer agents, the enhancement of drug sensitivity by overcoming drug resistance, and the targeting of therapy based on genomic profiles, which will lead to the complete curing of primary breast cancer. ABSTRACT: The treatment of primary breast cancer has evolved over the past 50 years based on the concept that breast cancer is a systemic disease, with the escalation of adjuvant and neoadjuvant therapies and de-escalation of breast cancer surgery. Despite the development of these therapies, recurrence with distant metastasis during the 10 years after surgical treatment is observed, albeit infrequently. Recent advances in genomic analysis based on circulating tumor cells and circulating tumor DNA have enabled the development of targeted therapies based on genetic mutations in residual tumor cells. A paradigm shift involving the application of neoadjuvant chemotherapy (NAC) has enabled the prediction of treatment response and long-term prognoses; additional adjuvant chemotherapy targeting remaining tumor cells after NAC improves survival. The activation of antitumor immunity by anticancer agents may be involved in the eradication of residual tumor cells. Elucidation of the manner in which antitumor immunity is induced by anticancer agents and unknown factors, and the overcoming of drug resistance via the targeted eradication of residual tumor cells based on genomic profiles, will inevitably lead to the achievement of 0% distant recurrence and a complete cure for primary breast cancer.