Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer

Peter A Argenta, Inhwa Um, Charlene Kay, David Harrison, Dana Faratian, Thanasak Sueblinvong, Melissa A Geller, Simon P. Langdon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background Anti-estrogen therapy appears to have efficacy in a subset of ovarian cancers, as demonstrated in multiple phase II studies. Identifying sensitive patients early in treatment may allow for targeted, low-toxicity primary therapy or prevention of recurrence. We have previously demonstrated that the likelihood of response to letrozole could be improved by patient selection based on estrogen-pathway marker expression. We sought to identify ovarian cancer biomarkers that might indicate sensitivity to fulvestrant, an estrogen receptor antagonist. Methods Tissue samples from the primary tumors of patients enrolled in a phase II study of fulvestrant for the treatment of multiply-recurrent ovarian cancer were embedded randomly in a tissue microarray (TMA). Estrogen receptor alpha (ERα) expression was assessed by both conventional immunohistochemistry (IHC) and quantitative immunofluorescence (IF) (AQUA) while expression of 14 other estrogen-regulated markers was assessed by quantitative IF and correlated with clinical outcomes. Results Almost half of patients experienced clinical benefit (CR + PR + SD) at 90 days despite a median of 5 previous treatment regimens. 24 of 26 patient samples were available and included in the TMA. ERα expression, measured either by conventional IHC or by AQUA analysis, was associated with clinical benefit, while TFF1 and vimentin expression (measured by IF AQUA score) was predictive of progression-free survival. Conclusions These results confirm our previous observation that clinical ovarian cancer includes a subset of tumors with sensitivity to estrogen pathway blockade. Expression profile of sensitive tumors appears to be detectably different from insensitive tumors, suggesting that further improvements in treatment efficacy can be obtained through appropriate patient selection.

Original languageEnglish (US)
Pages (from-to)368-373
Number of pages6
JournalGynecologic oncology
Volume131
Issue number2
DOIs
StatePublished - Nov 1 2013

Fingerprint

Ovarian Neoplasms
Estrogens
Fluorescent Antibody Technique
letrozole
Estrogen Receptor alpha
Patient Selection
Neoplasms
Immunohistochemistry
Therapeutics
Vimentin
Tumor Biomarkers
Disease-Free Survival
fulvestrant
Recurrence

Keywords

  • Biological therapy
  • Endocrine therapy
  • Estrogen receptor
  • Fulvestrant
  • Ovarian cancer
  • Vimentin

Cite this

Argenta, P. A., Um, I., Kay, C., Harrison, D., Faratian, D., Sueblinvong, T., ... Langdon, S. P. (2013). Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer. Gynecologic oncology, 131(2), 368-373. https://doi.org/10.1016/j.ygyno.2013.07.099

Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer. / Argenta, Peter A; Um, Inhwa; Kay, Charlene; Harrison, David; Faratian, Dana; Sueblinvong, Thanasak; Geller, Melissa A; Langdon, Simon P.

In: Gynecologic oncology, Vol. 131, No. 2, 01.11.2013, p. 368-373.

Research output: Contribution to journalArticle

Argenta, PA, Um, I, Kay, C, Harrison, D, Faratian, D, Sueblinvong, T, Geller, MA & Langdon, SP 2013, 'Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer', Gynecologic oncology, vol. 131, no. 2, pp. 368-373. https://doi.org/10.1016/j.ygyno.2013.07.099
Argenta, Peter A ; Um, Inhwa ; Kay, Charlene ; Harrison, David ; Faratian, Dana ; Sueblinvong, Thanasak ; Geller, Melissa A ; Langdon, Simon P. / Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer. In: Gynecologic oncology. 2013 ; Vol. 131, No. 2. pp. 368-373.
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