Abstract P3-04-15: Ethinylestradiol treatment downregulates ER and upregulates PgR; Immunohistochemical analysis in postmenopausal breast cancer tissues after prior long-term estrogen-deprivation therapy

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Abstract Background: Estrogen receptor (ER) positive breast cancer can often be treated by hormone therapy; however a certain population of ER-positive patients becomes resistant to hormone therapy after long-term hormone treatment. Ethinylestradiol (EE2) is a derivative of estrogen which has shown promising effects on in these patients. Methods: We successfully obtained tissue samples from 6 patients undergoing EE2 treatment and examined 13 well-known breast cancer-related factors by analyzing their gene expression and by immunohistochemistry. Of the 6 patients, 5 responded but one patient did not. Results: Before EE2 treatment, staining for both ER and androgen receptor (AR) was strong in the nucleus, with weak staining of the progesterone receptor (PgR). EE2 treatment significantly down-regulated ER and up-regulated PgR while nuclear and cytosolic AR were oppositely down- and up-regulated, respectively, by EE2. Cytosolic staining of BRCA1 was significantly up-regulated by EE2 whereas nuclear staining tended to decrease. Individual comparisons suggested less induction of PgR and decreasing AKT but increasing pAKT in the non-responder following EE2 treatment. Conclusion: Our observations revealed that EE2 activated ER downstream genes, although it did not stimulate cell growth. This suggests that hormone resistant cells might receive growth signals from a non-genomic pathway and this may be reflected in their sensitivity to EE2 treatment. Citation Format: Hirotaka Iwase, Yoko Omoto, Takashi Takeshita, Mutsuko Yamamoto-Ibusuki, Mitsuhiro Hayashi, Aiko Sueta, Saori Fujiwara, Yutaka Yamamoto. Ethinylestradiol treatment downregulates ER and upregulates PgR; Immunohistochemical analysis in postmenopausal breast cancer tissues after prior long-term estrogen-deprivation therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-15.