TY - JOUR T1 - Estrogen Down-regulator Fulvestrant Potentiates Antitumor Activity of Fluoropyrimidine in Estrogen-responsive MCF-7 Human Breast Cancer Cells JF - In Vivo JO - In Vivo SP - 1439 LP - 1445 DO - 10.21873/invivo.11622 VL - 33 IS - 5 AU - MAMORU NUKATSUKA AU - HITOSHI SAITO AU - SHINZABURO NOGUCHI AU - TEIJI TAKECHI Y1 - 2019/09/01 UR - http://iv.iiarjournals.org/content/33/5/1439.abstract N2 - Background: Endocrine therapy is clinically administered in hormone-responsive breast cancer. Combinations of fluoropyrimidine S-1 and an aromatase inhibitor or anti-estrogen are considered beneficial in Japan. Herein we assessed new combinations of S-1 and fulvestrant. Patients and Methods: Cytotoxicity of fulvestrant and 5-fluorouracil (5-FU) was assessed in hormone-responsive (MCF-7) and non-responsive (MDA-MB-231) breast cancer cell cultures. Fulvestrant and S-1 were evaluated for antitumor activity in mice and their effects on estrogen receptor (ER)-α and progesterone receptor (PgR) levels in MCF-7 xenografts using immunohistochemical methods. Results: Fulvestrant inhibited growth of MCF-7, but not of MDA-MB-231 xenografts. Combinations of 5-FU and fulvestrant were superior to monotherapy in vitro. In vivo antitumor activity of S-1/fulvestrant combination therapy was significantly (p<0.05) enhanced compared to that of both monotherapies. Fulvestrant partially down-regulated expression of ERα and PgR, but in combination with S-1, it almost completely blocked their expression. Conclusion: Chemo-endocrine combination therapy using S-1 and fulvestrant is beneficial in estrogen-responsive breast cancer. ER -