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Purpose: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ERα) in approximately 80% of HGSOC and some small but promising clinical trials of endocrine therapy, ERα has been understudied as a target in this disease. We sought to identify hormone-responsive, ERα-dependent HGSOC.Experimental Design: We characterized endocrine response in HGSOC cells across culture conditions [ two-dimensional (2D), three-dimensional (3D), forced suspension] and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression. Estrogen-regulated transcriptome data were overlapped with public datasets to develop a comprehensive panel of ERα target genes. Expression of this panel and ERα H-score were assessed in HGSOC samples from patients who received endocrine therapy. Time on endocrine therapy was used as a surrogate for clinical response.Results: Proliferation is ERα-regulated in HGSOC cells in vitro and in vivo, and is partly dependent on 3D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ERα targets. The selective ERα downregulator (SERD) fulvestrant is more effective than tamoxifen in blocking ERα action. ERα H-score is predictive of efficacy of endocrine therapy, and this prediction is further improved by inclusion of target gene expression, particularly IGFBP3.Conclusions: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ERα and endocrine responsiveness. Assessing ERα function (e.g., IGFBP3 expression) in conjunction with H-score may help select patients who would benefit from endocrine therapy. Preclinical data suggest that SERDs might be more effective than tamoxifen. Clin Cancer Res; 23(14); 3802–12. ©2017 AACR.

Supplementary File 3 contains the available pre- and post-treatment CA-125 data for our patient cohort.

Supplementary File 1 contains the genes included in the "EndoRx" NanoString code set.

This document contains the supplementary figures for the manuscript.

Terrestrial anurans, with their typically short limbs, heavy-set bodies and absent claws or toe pads are incongruous tree climbers, but even occasional arboreal locomotion could offer substantial advantages for evading predators or accessing new shelter or food resources. Despite recent interest, arboreal behaviour remains rarely and unsystematically described for terrestrial amphibians in Europe, likely due to fundamental differences in survey methods and therefore a lack of field data. However, other taxa surveys specifically target trees and tree cavities. We undertook collaborations and large-scale data searches with two major citizen science projects surveying for arboreal mammals in Britain to investigate potential tree climbing by amphibians at a national scale. Remarkably, we found widespread arboreal usage by amphibians in England and Wales, with occupancy of hazel dormouse (Muscardinus avellenarius) nest boxes, tree cavities investigated as potential bat roosts and even a bird nest, by common toads (Bufo bufo), but few additional records of frogs or newts. Of the 277–400 sites surveyed annually for dormice since 2009 at least 18 sites had amphibians recorded in nest boxes while of the 1388 trees surveyed for bats a total 1.4% (19 trees) had toads present. Common toads were found using cavities in seven tree species and especially goat willow (Salix caprea). Toads are potentially attracted to tree cavities and arboreal nests because they provide safe and damp microenvironments which can support an abundance of invertebrate prey but the importance of such tree microhabitats for toad conservation remains unknown and our results should be interpreted cautiously. We encourage expanding and linking of unrelated biodiversity monitoring surveys and citizen science initiatives as valuable tools for investigating ecological traits and interactions.

Purpose: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ERα) in approximately 80% of HGSOC and some small but promising clinical trials of endocrine therapy, ERα has been understudied as a target in this disease. We sought to identify hormone-responsive, ERα-dependent HGSOC. Experimental Design: We characterized endocrine response in HGSOC cells across culture conditions [ two-dimensional (2D), three-dimensional (3D), forced suspension] and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression. Estrogen-regulated transcriptome data were overlapped with public datasets to develop a comprehensive panel of ERα target genes. Expression of this panel and ERα H-score were assessed in HGSOC samples from patients who received endocrine therapy. Time on endocrine therapy was used as a surrogate for clinical response. Results: Proliferation is ERα-regulated in HGSOC cells in vitro and in vivo, and is partly dependent on 3D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ERα targets. The selective ERα downregulator (SERD) fulvestrant is more effective than tamoxifen in blocking ERα action. ERα H-score is predictive of efficacy of endocrine therapy, and this prediction is further improved by inclusion of target gene expression, particularly IGFBP3. Conclusions: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ERα and endocrine responsiveness. Assessing ERα function (e.g., IGFBP3 expression) in conjunction with H-score may help select patients who would benefit from endocrine therapy. Preclinical data suggest that SERDs might be more effective than tamoxifen. Clin Cancer Res; 23(14); 3802–12. ©2017 AACR.