Flutamide and biomarkers in women at high risk for ovarian cancer

Preclinical and clinical evidence

Christine Gruessner, Angelika Gruessner, Katherine Glaser, Nisreen AbuShahin, Yi Zhou, Cynthia Laughren, Heather Wright, Samantha Pinkerton, Xiaofang Yi, Jha'Nae Stoffer, Masoud Azodi, Wenxin Zheng, Setsuko K. Chambers

Research output: Contribution to journalArticle

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Abstract

We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation.Weshowed that androgen ablation of male mice led to a 24-fold decrease in tumor burden from serous ovarian cells. In a phase II study, we studied the effect of preoperative flutamide treatment (125 mg/day × 6 weeks) in 12womenversus 47 controls, 47% with BRCA mutation. We analyzed immunohistochemical scores of candidate proteins CSF-1, CSF-1R, and ErbB4 in the epithelium and stroma of fallopian tube, ovary, and ovarian endosalpingiosis. Flutamide decreased the levels, notably, of CSF-1 and ErbB4 in ovarian stroma (P ≤ 0.0006) and ovarian endosalpingiosis (P≤0.01), ErbB4 in ovarian epithelium (P=0.006), and CSF-1R in ovarian endosalpingiosis (P= 0.009). Our logistic regression model clearly distinguished the flutamide patients from controls (P ≤ 0.0001). Our analysis of the precision of this model of CSF-1 and ErbB4 expression in ovarian stroma achieved 100% sensitivity and 97% specificity (AUC = 0.99). Thus, our data suggest that a short 6-week exposure of flutamide reversed elevated levels of CSF-1 and ErbB4 (both of which we had previously found correlated with high risk status). CSF-1 and ErbB4 in ovarian stroma led to a model with high predictive value for flutamide sensitivity. The effect of flutamide on marker expression in ovarian endosalpingiosis, previously associated with BRCA carrier status, suggests that ovarian endosalpingiosis may be a latent precursor to pelvic serous cancers.

Original languageEnglish (US)
Pages (from-to)896-905
Number of pages10
JournalCancer Prevention Research
Volume7
Issue number9
DOIs
StatePublished - Jan 1 2014

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Flutamide
Ovarian Neoplasms
Macrophage Colony-Stimulating Factor
Biomarkers
Androgens
Epithelium
Logistic Models
Pelvic Neoplasms
Fallopian Tubes
Tumor Burden
Area Under Curve
Ovary
Sensitivity and Specificity
Mutation
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Gruessner, C., Gruessner, A., Glaser, K., AbuShahin, N., Zhou, Y., Laughren, C., ... Chambers, S. K. (2014). Flutamide and biomarkers in women at high risk for ovarian cancer: Preclinical and clinical evidence. Cancer Prevention Research, 7(9), 896-905. https://doi.org/10.1158/1940-6207.CAPR-13-0408

Flutamide and biomarkers in women at high risk for ovarian cancer : Preclinical and clinical evidence. / Gruessner, Christine; Gruessner, Angelika; Glaser, Katherine; AbuShahin, Nisreen; Zhou, Yi; Laughren, Cynthia; Wright, Heather; Pinkerton, Samantha; Yi, Xiaofang; Stoffer, Jha'Nae; Azodi, Masoud; Zheng, Wenxin; Chambers, Setsuko K.

In: Cancer Prevention Research, Vol. 7, No. 9, 01.01.2014, p. 896-905.

Research output: Contribution to journalArticle

Gruessner, C, Gruessner, A, Glaser, K, AbuShahin, N, Zhou, Y, Laughren, C, Wright, H, Pinkerton, S, Yi, X, Stoffer, JN, Azodi, M, Zheng, W & Chambers, SK 2014, 'Flutamide and biomarkers in women at high risk for ovarian cancer: Preclinical and clinical evidence', Cancer Prevention Research, vol. 7, no. 9, pp. 896-905. https://doi.org/10.1158/1940-6207.CAPR-13-0408
Gruessner, Christine ; Gruessner, Angelika ; Glaser, Katherine ; AbuShahin, Nisreen ; Zhou, Yi ; Laughren, Cynthia ; Wright, Heather ; Pinkerton, Samantha ; Yi, Xiaofang ; Stoffer, Jha'Nae ; Azodi, Masoud ; Zheng, Wenxin ; Chambers, Setsuko K. / Flutamide and biomarkers in women at high risk for ovarian cancer : Preclinical and clinical evidence. In: Cancer Prevention Research. 2014 ; Vol. 7, No. 9. pp. 896-905.
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AU - Zhou, Yi

AU - Laughren, Cynthia

AU - Wright, Heather

AU - Pinkerton, Samantha

AU - Yi, Xiaofang

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