title: Immunohistochemical analysis in ethinylestradiol-treated breast cancers after prior long-term estrogen-deprivation therapy.
abstract: BACKGROUND
  Estrogen receptor (ER) positive breast cancer can often be treated by hormone therapy; however a certain population of ER-positive patients become resistant to hormone therapy after long-term hormone treatment. Ethinylestradiol (EE2) is a derivative of estrogen, which has shown promising effects 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 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, and the progesterone receptor (PgR) was almost no staining. EE2 treatment significantly down-regulated ER and up-regulated PgR while nuclear and cytosolic AR were oppositely down- and up-regulated, respectively. 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.
  
  
  CONCLUSIONS
  Our observations revealed that EE2 activated ER downstream genes; however 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.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan ; Department of Endocrinological and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji Agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto, 602-0841 Japan ; Department of Breast Surgery, Tanabe Central Hospital, 6-1-6, Tanabe-Chuo, Kyotanabe-city, Kyoto 610-0334 Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Omoto
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeshita
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sueta
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Endocrinological and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji Agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto, 602-0841 Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
keywords: Endocrine therapy; Estrogen receptor; Estrogen treatment resistance; Ethinylestradiol; Metastatic breast cancer