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.
Keywords: Breast cancer; S-1; chemo-endocrine combination therapy; chemotherapy; endocrine therapy; estrogen receptor; fulvestrant; progesterone receptor.
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.