Serum Bone Biomarkers in Early Breast Cancer and Risk of Bone Metastasis


Key Points

  • P1NP, CTX, and 1-CTP were prognostic for bone recurrence as continuous variables.
  • High P1NP and CTX were prognostic as categorical variables.

In a study reported in the Journal of the National Cancer Institute, Brown et al found that the serum bone biomarkers P1NP, CTX, and 1-CTP showed good prognostic ability for bone metastasis in patients in the phase III AZURE (BIG01/04) trial of adjuvant zoledronic acid in early breast cancer.

Study Details

The study involved measurement of markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) in pretreatment blood samples from 872 patients from the AZURE trial.

In the trial, 3,360 women with stage II or III breast cancer were randomized to standard adjuvant treatment with or without zoledronic acid for 5 years; zoledronic acid was associated with improved invasive disease-free survival in patients who were > 5 years postmenopausal at diagnosis.

Prognostic Ability

As continuous variables, P1NP (P = .006), CTX (P = .009), and 1-CTP (P = .008) were prognostic for bone recurrence at any time. With regard to discriminatory ability, c-indices were 0.57 for P1NP, 0.57 for CTX, and 0.57 for 1-CTP. Baseline values were above normal for P1NP, CTX, and 1-CTP in 27.3%, 30.0%, and 50.5% of patients, respectively. As categorical variable, high baseline P1NP (> 70 ng/mL; P = .03) and CTX (> 0.299 ng/mL; P = .03) but not 1-CTP (> 4.2 ng/mL; P = .10) were also prognostic for bone recurrence at any time. None of the three markers was prognostic for overall distant recurrence, and none of the markers was predictive of zoledronic acid treatment benefit.

The investigators concluded, “Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study.”

The study was supported by Cancer Research UK and Novartis Pharmaceuticals.

Janet E. Brown, MD, of the Academic Unit of Clinical Oncology, University of Sheffield, is the corresponding author for the Journal of the National Cancer Institute article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.