Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1988 Aug;58(2):205–210. doi: 10.1038/bjc.1988.194

Biochemical prediction of response of bone metastases to treatment.

R E Coleman 1, K B Whitaker 1, D W Moss 1, G Mashiter 1, I Fogelman 1, R D Rubens 1
PMCID: PMC2246751  PMID: 3262366

Abstract

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment.

Full text

PDF
205

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Campbell F. C., Blamey R. W., Woolfson A. M., Elston C. W., Hosking D. J. Calcium excretion (CaE) in metastatic breast cancer. Br J Surg. 1983 Apr;70(4):202–204. doi: 10.1002/bjs.1800700405. [DOI] [PubMed] [Google Scholar]
  2. Coleman R. E., Rubens R. D. Bone metastases and breast cancer. Cancer Treat Rev. 1985 Dec;12(4):251–270. doi: 10.1016/0305-7372(85)90008-8. [DOI] [PubMed] [Google Scholar]
  3. Coleman R. E., Rubens R. D. The clinical course of bone metastases from breast cancer. Br J Cancer. 1987 Jan;55(1):61–66. doi: 10.1038/bjc.1987.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coombes R. C., Dady P., Parsons C., McCready V. R., Ford H. T., Gazet J. C., Powles T. J. Assessment of response of bone metastases to systemic treatment in patients with breast cancer. Cancer. 1983 Aug 15;52(4):610–614. doi: 10.1002/1097-0142(19830815)52:4<610::aid-cncr2820520406>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  5. Grant C. S., Hoare S. A., Millis R. R., Hayward J. L., Wang D. Y. Urinary hydroxyproline and prognosis in human breast cancer. Br J Surg. 1984 Feb;71(2):105–108. doi: 10.1002/bjs.1800710208. [DOI] [PubMed] [Google Scholar]
  6. Hortobagyi G. N., Libshitz H. I., Seabold J. E. Osseous metastases of breast cancer. Clinical, biochemical, radiographic, and scintigraphic evaluation of response to therapy. Cancer. 1984 Feb 1;53(3):577–582. doi: 10.1002/1097-0142(19840201)53:3<577::aid-cncr2820530335>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  7. Moss D. W., Whitby L. G. A simplified heat-inactivation method for investigating alkaline phosphatase isoenzymes in serum. Clin Chim Acta. 1975 May 15;61(1):63–71. doi: 10.1016/0009-8981(75)90398-8. [DOI] [PubMed] [Google Scholar]
  8. Mundy G. R. The hypercalcemia of malignancy. Kidney Int. 1987 Jan;31(1):142–155. doi: 10.1038/ki.1987.21. [DOI] [PubMed] [Google Scholar]
  9. Palazzo S., Liguori V., Molinari B. Is the carcinoembryonic antigen test a valid predictor of response to medical therapy in disseminated breast cancer? Tumori. 1986 Oct 31;72(5):515–518. doi: 10.1177/030089168607200512. [DOI] [PubMed] [Google Scholar]
  10. Peacock M., Robertson W. G., Nordin B. E. Relation between serum and urinary calcium with particular reference to parathyroid activity. Lancet. 1969 Feb 22;1(7591):384–386. doi: 10.1016/s0140-6736(69)91353-1. [DOI] [PubMed] [Google Scholar]
  11. Price P. A., Parthemore J. G., Deftos L. J. New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest. 1980 Nov;66(5):878–883. doi: 10.1172/JCI109954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ransohoff D. F., Feinstein A. R. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. N Engl J Med. 1978 Oct 26;299(17):926–930. doi: 10.1056/NEJM197810262991705. [DOI] [PubMed] [Google Scholar]
  13. Rossleigh M. A., Lovegrove F. T., Reynolds P. M., Byrne M. J., Whitney B. P. The assessment of response to therapy of bone metastases in breast cancer. Aust N Z J Med. 1984 Feb;14(1):19–22. doi: 10.1111/j.1445-5994.1984.tb03578.x. [DOI] [PubMed] [Google Scholar]
  14. Yarrison G., Mertens B. F., Mathies J. C. New diagnostic use of bone marrow acid and alkaline phosphatase. Am J Clin Pathol. 1976 Oct;66(4):667–671. doi: 10.1093/ajcp/66.4.667. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES