BACKGROUND: Targeting growth factor and survival pathways may delay endocrine-resistance in estrogen receptor-positive breast cancer. MATERIALS & METHODS: A pilot Phase II study adding sorafenib to endocrine therapy in 11 patients with metastatic estrogen receptor-positive breast cancer was conducted. Primary end point was response by RECIST after 3 months of sorafenib. Secondary end points included safety, time to progression and biomarker modulation. The study closed early owing to slow accrual. RESULTS: Eight out of 11 patients had progressive disease on study entry and three had stable disease. Of the ten evaluable patients, seven experienced stable disease (70%) and three experienced progressive diseas (30%), with a median time to progression of 6.1 months (8.4 months in the seven patients on tamoxifen). The serum samples demonstrated a significant reduction in VEGF receptor 2 and PDGF receptor-α. Microarray analysis identified 32 suppressed genes, no induced genes and 29 enriched Kyoto Encyclopedia of Genes and Genomes pathways. CONCLUSION: The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies.
BACKGROUND: Targeting growth factor and survival pathways may delay endocrine-resistance in estrogen receptor-positive breast cancer. MATERIALS & METHODS: A pilot Phase II study adding sorafenib to endocrine therapy in 11 patients with metastatic estrogen receptor-positive breast cancer was conducted. Primary end point was response by RECIST after 3 months of sorafenib. Secondary end points included safety, time to progression and biomarker modulation. The study closed early owing to slow accrual. RESULTS: Eight out of 11 patients had progressive disease on study entry and three had stable disease. Of the ten evaluable patients, seven experienced stable disease (70%) and three experienced progressive diseas (30%), with a median time to progression of 6.1 months (8.4 months in the seven patients on tamoxifen). The serum samples demonstrated a significant reduction in VEGF receptor 2 and PDGF receptor-α. Microarray analysis identified 32 suppressed genes, no induced genes and 29 enriched Kyoto Encyclopedia of Genes and Genomes pathways. CONCLUSION: The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies.
Authors: José Baselga; Mario Campone; Martine Piccart; Howard A Burris; Hope S Rugo; Tarek Sahmoud; Shinzaburo Noguchi; Michael Gnant; Kathleen I Pritchard; Fabienne Lebrun; J Thaddeus Beck; Yoshinori Ito; Denise Yardley; Ines Deleu; Alejandra Perez; Thomas Bachelot; Luc Vittori; Zhiying Xu; Pabak Mukhopadhyay; David Lebwohl; Gabriel N Hortobagyi Journal: N Engl J Med Date: 2011-12-07 Impact factor: 91.245
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
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Authors: Charlton Cooper; Guang-Yu Liu; Yu-Lian Niu; Sylvia Santos; Leigh C Murphy; Peter H Watson Journal: Clin Cancer Res Date: 2004-12-15 Impact factor: 12.531
Authors: Rachel Schiff; Suleiman A Massarweh; Jiang Shou; Lavina Bharwani; Syed K Mohsin; C Kent Osborne Journal: Clin Cancer Res Date: 2004-01-01 Impact factor: 12.531
Authors: S Kato; H Endoh; Y Masuhiro; T Kitamoto; S Uchiyama; H Sasaki; S Masushige; Y Gotoh; E Nishida; H Kawashima; D Metzger; P Chambon Journal: Science Date: 1995-12-01 Impact factor: 47.728
Authors: Maria Carolina Mangini Prado; Sofia de Almeida Losant Macedo; Giulia Gumiero Guiraldelli; Patricia de Faria Lainetti; Antonio Fernando Leis-Filho; Priscila Emiko Kobayashi; Renee Laufer-Amorim; Carlos Eduardo Fonseca-Alves Journal: Front Oncol Date: 2019-12-19 Impact factor: 6.244