Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis

Breast Cancer Res Treat. 2017 Feb;161(3):501-513. doi: 10.1007/s10549-016-4068-5. Epub 2016 Dec 3.

Abstract

Purpose: The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy.

Methods: In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history.

Results: The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated.

Conclusions: Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Keywords: Aromatase inhibitor; Biomarker; Bone; Breast cancer; Tamoxifen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Biomarkers, Tumor
  • Bone Density
  • Bone Diseases / complications*
  • Bone Diseases / epidemiology
  • Bone Diseases / metabolism*
  • Bone Diseases / pathology
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary
  • Bone Remodeling*
  • Breast Neoplasms / complications*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology*
  • Exercise
  • Female
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology
  • Fractures, Bone / metabolism
  • Humans
  • Life Style
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Osteoporosis / epidemiology
  • Osteoporosis / etiology
  • Osteoporosis / metabolism
  • Postmenopause
  • Premenopause
  • Risk Factors

Substances

  • Biomarkers
  • Biomarkers, Tumor