Survival in older women with early stage breast cancer receiving low-dose bisphosphonates or denosumab

Cancer. 2020 Sep 1;126(17):3929-3938. doi: 10.1002/cncr.33035. Epub 2020 Jun 23.

Abstract

Background: Bisphosphonates and denosumab, as adjuvant therapy in breast cancer, have been associated in some studies with improved cancer outcomes. The potential benefits of these drugs used at the lower doses commonly given for osteoporosis have not been established. The objective of this study was to investigate the association between therapy with bone-modifying agents (BMAs) and survival in older women with early breast cancer.

Methods: The authors conducted a retrospective cohort study of women aged ≥66 years with breast cancer who were included in the Surveillance, Epidemiology, and End Results and Texas Cancer Registry Medicare-linked databases. Associations were examined between the receipt of BMAs at dosages indicated for osteoporosis within 2 years after diagnosis and overall and breast cancer-specific survival. Cox proportional hazards models and propensity score adjustment and matching were used for the analyses.

Results: Of the 37,724 women included, 7925 (21%) received at least 6 months of a BMA within the first 2 years of breast cancer diagnosis, including bisphosphonates only in 6898 women (80.7%), denosumab only in 1204 (15.2%), and both classes of BMAs in 323 (4.1%). The median follow-up was 64 months. The receipt of a bisphosphonate was associated with improved overall survival (hazard ratio [HR], 0.87; 95% CI, 0.82-0.93) and breast cancer-specific survival (HR, 0.77; 95% CI, 0.64-0.92) after multivariable adjustment. Benefits were primarily seen for patients who had stage II and III disease. No benefits were observed with denosumab (stage II: HR, 1.05 [95% CI, 0.90-1.22]; stage III: HR, 1.09 [95% CI, 0.66-1.82]).

Conclusions: Bisphosphonates at the doses recommended for osteoporosis are associated with improved survival in older postmenopausal women with early breast cancer.

Keywords: adjuvant therapy; bisphosphonates; breast cancer; denosumab; osteoporosis.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / pathology
  • Denosumab / administration & dosage*
  • Diphosphonates / administration & dosage*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Medicare
  • Neoplasm Staging
  • Osteoporosis / complications
  • Osteoporosis / drug therapy*
  • Osteoporosis / epidemiology
  • Osteoporosis / pathology
  • Progression-Free Survival
  • Proportional Hazards Models
  • Texas / epidemiology
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Denosumab