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Clinical Trial of Acolbifene in Premenopausal Women at High Risk for Breast Cancer.
Fabian, Carol J; Kimler, Bruce F; Zalles, Carola M; Phillips, Teresa A; Metheny, Trina; Petroff, Brian K; Havighurst, Thomas C; Kim, KyungMann; Bailey, Howard H; Heckman-Stoddard, Brandy M.
Afiliação
  • Fabian CJ; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
  • Kimler BF; Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas. bkimler@kumc.edu.
  • Zalles CM; Mercy Hospital, Miami, Florida.
  • Phillips TA; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
  • Metheny T; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
  • Petroff BK; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
  • Havighurst TC; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison, Madison, Wisconsin.
  • Kim K; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison, Madison, Wisconsin.
  • Bailey HH; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
  • Heckman-Stoddard BM; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
Cancer Prev Res (Phila) ; 8(12): 1146-55, 2015 Dec.
Article em En | MEDLINE | ID: mdl-26391916
ABSTRACT
The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. To do so, we assessed change in proliferation in benign breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia ± atypia and ≥2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6-8 months, and then had benign breast tissue and blood risk biomarkers reassessed. Ki-67 decreased from a median of 4.6% [interquartile range (IQR), 3.1%-8.5%] at baseline to 1.4% (IQR, 0.6%-3.5%) after acolbifene (P < 0.001; Wilcoxon signed-rank test), despite increases in bioavailable estradiol. There were also significant decreases in expression (RT-qPCR) of estrogen-inducible genes that code for pS2, ERα, and progesterone receptor (P ≤ 0.026). There was no significant change in serum IGF1, IGFBP3, IGF1IGFBP3 ratio, or mammographic breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spine bone density (DEXA) and an increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal side effects, suggesting a phase IIB placebo-controlled trial evaluating it further for breast cancer prevention.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperidinas / Mama / Neoplasias da Mama / Pré-Menopausa / Moduladores Seletivos de Receptor Estrogênico / Proliferação de Células Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperidinas / Mama / Neoplasias da Mama / Pré-Menopausa / Moduladores Seletivos de Receptor Estrogênico / Proliferação de Células Idioma: En Ano de publicação: 2015 Tipo de documento: Article