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Additional therapy following definitive breast surgery after primary systemic chemotherapy (PSC) has not been correctly evaluated. Two unsolved problems regarding additional chemotherapy following PSC in advanced breast cancer are the subjects of this article. First is the prognostic impact of additional chemotherapy after surgery in patients with residual disease after completion of standard PSC, and second is the use of oral anticancer drugs such as S-1, which are known as metronomic chemotherapy, in this setting. Although there are many ongoing trials for breast cancer patients with residual disease after PSC in various subtypes, survival benefit has not been validated in clinical trials. Orally effective anticancer drugs such as S-1 and capecitabine can be further candidates for additional postoperative chemotherapy after PSC. Further studies are needed to evaluate the usefulness of these metronomic chemotherapies in this setting.