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Heparanase Activity and Bone Loss in Postmenopausal Breast Cancer Patients

Department of Medical Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey

Ozden Altundag

Houston, TX

Mauricio Z. Baptista

Department of Clinical Oncology, Hospital Maternidade De Campinas, Campinas, SP, Brazil

Serap Akyurek

Department of Radiation Oncology, Ankara University School of Medicine, Ankara, Turkey

To the Editor:

We read with great interest the study by Lønning et al¹ regarding the effects of 2 years of exemestane administration on bone mineral density, bone biomarkers, plasma lipids, coagulation factors, and homocysteine in postmenopausal women with low-risk, surgically treated early breast cancer (n = 129) or ductal carcinoma-in-situ (n = 18). They found modestly increased bone loss from the femoral neck and a nonsignificant increase in bone loss from the vertebrae in patients treated with exemestane comparing to placebo group. Although the patients in treatment and placebo groups were comparable in terms of patients' and tumor characteristics, heparanase activity in these women might alter the interpretation of results in this study. Heparanase is an enzyme that cleaves heparan sulfate and through this activity promotes tumor growth, angiogenesis, invasion, and metastasis in several tumor types. In human breast cancer patients, heparanase expression is associated with sentinel lymph node metastases. Recently, Kelly et al² revealed a novel role for heparanase in skeletal complications that accompany breast cancer. They discovered that breast tumors having elevated levels of heparanase and growing in the mammary fat pads promote bone remodeling before metastases or even microscopic tumor foci can be detected in the bone marrow. In contrast, animals injected with control cells that express low levels of heparanase activity exhibit no systemic increase in bone resorption even when the primary tumor burden is large. The mechanism underlying the heparanase-mediated increase in bone resorption is the stimulation of osteoclastogenesis.

Women with breast cancer might have a predilection to develop osteoporosis affecting bone turnover thorough increased heparanase secretion by breast cancer cells even without developing bone metastases. Therefore, stratification of the patients according to their heparanase activity may further strengthen the results of this study.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Lønning PE, Geisler J, Krag LE, et al: Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol 23:5126-5137, 2005[Abstract/Free Full Text]

2. Kelly T, Suva LJ, Huang Y, et al: Expression of heparanase by primary breast tumors promotes bone resorption in the absence of detectable bone metastases. Cancer Res 65:5778-5784, 2005[Abstract/Free Full Text]

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• In Reply:
  Per Eystein Lønning and Jurgen Geisler
  JCO 2005 23: 8917-8918 [Full Text]

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