title: Risk Factors for Developing Skeletal-Related Events in Breast Cancer Patients With Bone Metastases Undergoing Treatment With Bone-Modifying Agents.
abstract: BACKGROUND
  Bone-modifying agents (BMAs) reduce the incidence of skeletal-related events (SREs) and are thus recommended for breast cancer patients with bone metastases. However, the risk factors for SREs during BMA treatment are not well-understood. This study evaluated the number and timing of SREs from case studies to identify these factors.
  
  
  METHODS
  The medical records of 534 women with breast cancer who developed bone metastases between 1999 and 2011 were reviewed. SREs were defined as a pathologic fracture, spinal cord compression, or the need for bone irradiation or surgery. Multiple variables were assessed and were analyzed by using the Cox proportional hazard analyses and the Andersen and Gill method.
  
  
  RESULTS
  Multivariate analyses for both the time to the first SRE and the primary and subsequent SRE frequency demonstrated that significant baseline risk factors included luminal B type disease, a history of palliative radiation therapy, BMA treatment within 2 years, and elevated serum calcium levels at the time of the initial BMA dose. Additionally, for the time to the first SRE and for the primary and subsequent SRE frequency, the presence of extraskeletal metastases and BMA administration initiation ≥6 months after the detection of bone metastases were also significant risk factors, respectively.
  
  
  CONCLUSIONS
  In breast cancer patients with bone metastases, more vigilant observation should be considered for patients with the identified risk factors. To reduce the risk for SRE, BMAs should be administered within 6 months of bone metastases diagnosis and before palliative radiation therapy.
  
  
  CONCLUSIONS
  Retrospectively, risk factors were identified for skeletal-related events (SREs) in breast cancer patients with bone metastasis who were treated with bone-modifying agents (BMAs). For the time to the first SRE and for the SRE frequency, presence of extraskeletal metastases and BMA initiation ≥6 months after the detection of bone metastases were risk factors, respectively. Luminal B type disease, a history of palliative radiation therapy, BMA treatment within 2 years, and elevated serum calcium levels at initial BMA dose were risk factors for both first SRE and SRE frequency. More vigilant observation should be considered for patients with these risk factors.
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan Department of Dermatology, University of Tsukuba, Tsukuba, Japan ryota621@hotmail.co.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Yonemori
authors.affiliation: Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirakawa
authors.affiliation: Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Kinoshita
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodaira
authors.affiliation: Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Harukaze
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Yunokawa
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimizu
authors.affiliation: Department of Dermatology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005598:Fractures, Spontaneous / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D000077268:Pamidronate; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate
keywords: Bone metastases; Bone-modifying agent; Breast cancer; Risk factor; Skeletal-related event