Natural history of malignant bone disease in breast cancer and the use of cumulative mean functions to measure skeletal morbidity.
BACKGROUND
Bone metastases are a common cause of skeletal morbidity in patients with advanced cancer. The pattern of skeletal morbidity is complex, and the number of skeletal complications is influenced by the duration of survival. Because many patients with cancer die before trial completion, there is a need for survival-adjusted methods to accurately assess the effects of treatment on skeletal morbidity.


METHODS
Recently, a survival-adjusted cumulative mean function model has been generated that can provide an intuitive graphic representation of skeletal morbidity throughout a study. This model was applied to the placebo-control arm of a pamidronate study in patients with malignant bone disease from breast cancer.


RESULTS
Analysis by bone lesion location showed that spinal metastases were associated with the highest cumulative mean incidence of skeletal-related events (SREs), followed by chest and pelvic metastases. Metastases located in the extremities were associated with an intermediate incidence of SREs, and those in the skull were associated with the lowest incidence of SREs.


CONCLUSIONS
Application of this model to data from the placebo arm of this trial revealed important insight into the natural history of skeletal morbidity in patients with bone metastases. Based on these observations, treatment for the prevention of SREs is warranted regardless of lesion location except for metastases on the skull.
Major
Pierre P
PP
McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada. pierre.major@jcc.hhsc.ca
Cook
Richard J
RJ
Lipton
Allan
A
Smith
Matthew R
MR
Terpos
Evangelos
E
Coleman
Robert E
RE
D000328:Adult; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009362:Neoplasm Metastasis; D000077268:Pamidronate
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate