title: Does estrogen play a role in response to adjuvant bone-targeted therapies?
abstract: Bone remains the most common site of breast cancer recurrence. The results of population studies, pre-clinical research and clinical studies in patients with metastatic disease provided a rationale for testing bone-targeted agents in the adjuvant setting. Despite the initial optimism, results from eight prospectively designed, randomized control studies powered to assess the value of adjuvant bone-targeted therapy in early breast cancer are conflicting. Data have shown that, where benefit exists, it tends to be in women with a "low estrogen environment", either through menopause or suppression of ovarian function. In this manuscript, we review clinical data supporting the hypothesis that estrogen levels may play a part in explaining the response of patients to bone-targeted agents in the adjuvant setting. The results presented to date suggest that there may be data supporting a unifying role for estrogen in adjuvant trials. However, in the absence of any prospective randomized trials in which estrogen data has been systematically collected we cannot specifically answer this question. We await the results of the Oxford overview analysis of individual patient data with interest.
authors.affiliation: Division of Medical Oncology, University of Ottawa and The Ottawa Hospital Cancer Center, Ottawa, Canada.
authors.forename: Kent
authors.initials: K
authors.lastname: Russell
authors.affiliation: Division of Medical Oncology and Hematology, University of Toronto and Princess Margaret Hospital, Toronto, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.affiliation: Department of Oncology, Tom Baker Cancer Center, University of Alberta, Calgary, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Paterson
authors.affiliation: Department of Medicine, St. Michael's Hospital, and University of Toronto, Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Josse
authors.affiliation: Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Addison
authors.affiliation: Division of Medical Oncology, University of Ottawa and The Ottawa Hospital Cancer Center, Ottawa, Canada.
authors.forename: Iryna
authors.initials: I
authors.lastname: Kuchuk
authors.affiliation: Division of Medical Oncology, University of Ottawa and The Ottawa Hospital Cancer Center, Ottawa, Canada; Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
keywords: Adjuvant therapy; Bisphosphonates; Bone-targeted therapies; Breast cancer; Estrogen