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Mammographic Density as a Surrogate Marker for the Effects of Hormone Therapy on Risk of Breast Cancer

¹ Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute; ² Division of Preventive Oncology, Cancer Care Ontario; ³ Imaging Research, Sunnybrook and Women's College Health Sciences Center, Toronto, Ontario, Canada; and ⁴ BC Cancer Agency, Vancouver, British Columbia, Canada

Requests for reprints: Norman F. Boyd, Ontario Cancer Institute, Room 10-415, 610 University Avenue, Toronto, Ontario, Canada M5G 2K9. Phone: 416-946-2945; Fax: 416-946-2024. E-mail: boyd{at}uhnres.utoronto.ca

Background: Some types of hormone therapy increase both risk of breast cancer and mammographic density, a risk factor for the disease, suggesting that mammographic density may be a surrogate marker for the effects of hormones on risk of breast cancer. This research was undertaken to determine whether the effect of hormone therapy on breast cancer risk is mediated by its effect on mammographic density.

Methods: Individually matched cases and controls from three nested case-control studies in breast screening populations were studied. Cases had developed invasive breast cancer at least 12 months after the initial screen. Information was collected on hormone use and other risk factors at the time of the baseline mammogram, and percent density was measured by a computer-assisted method.

Results: There were 1,748 postmenopausal women, of whom 426 (24.4%) were using hormones at the time of their initial screening mammogram. Current use of hormone therapy was associated with an increased risk of breast cancer (odds ratio, 1.26; 95% confidence interval, 1.0-1.6) that was little changed by adjustment for percent density in the baseline mammogram (odds ratio, 1.19; 95% confidence interval, 0.9-1.5). Percent density in the baseline mammogram was among cases greater in current users of hormones that in never-users (difference = 5.0%, P < 0.001), but the difference was smaller and nonsignificant in controls (difference = 1.6%, P = 0.3).

Conclusion: Although the effects of hormone therapy on mammographic density were greater in cases than controls, we did not find evidence that these effects were causally related to risk of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(5):961–6)

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