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Bone Monitoring Is Essential With Exemestane Use for Primary Prevention of Breast Cancer

Jill Stein
Published: Monday, Apr 23, 2012
Dr. Angela M. Cheung

Angela M. Cheung, MD

Monitoring bone health and ensuring adequate calcium and vitamin D intake in postmenopausal women who are taking exemestane for the primary prevention of breast cancer is essential, according to investigators of a recent study.

The recommendation is based on results showing that exemestane, a third-generation steroidal aromatase inhibitor, significantly worsened age-related bone loss roughly threefold, even though patients were receiving calcium and vitamin D supplementation.

Angela M. Cheung, MD, associate professor of Medicine at the University Health Network in Toronto, Canada, and coauthors elsewhere conducted a nested substudy of the Mammary Prevention 3 (MAP.3) Trial in order to determine exemestane’s effect on the skeleton.

Recently, the phase III MAP.3 trial demonstrated that oral exemestane 25 mg per day decreased the risk of invasive breast cancer (annual incidence, 0.19% for women treated with exemestane vs 0.55% for women treated with placebo; hazard ratio, 0.35; 95% CI, 0.18-0.70; P = .002) in healthy postmenopausal women at increased risk of breast cancer.

The substudy included 351 nonosteoporotic women, with a median age of 61.3 years. The primary endpoint was percentage change in volumetric bone mineral density (BMD) at the distal radius from baseline to 2 years by high-resolution peripheral quantitative computed tomography (CT).

The researchers said that they selected this endpoint because the distal radius is a common site for osteoporotic fractures, and because high-resolution peripheral quantitative CT offers a low-radiation detailed examination of bone density and structure in cortical and trabecular compartments—both of which are key determinants of bone strength.

Results showed that the mean percentage change in total volumetric BMD at the distal radius was -6.1% (95% CI, -7.0 to -5.2) in the exemestane group and -1.8% (-2.4 to -1.2) in the placebo group (difference, -4.3%; 95% CI, -5.3 to -3.2; P <.0001).

At the distal tibia, the mean percentage change in total volumetric BMD was -5.0% (95% CI, -5.5 to -4.4) in the exemestane group and -1.3% (95% CI, -1.7 to -1.0) in the placebo group (difference, -3.7%; 95% CI, -4.3 to -3.0; P <·0001). The mean percentage change in cortical thickness was -7.9% (SD = 7.3) in the exemestane group and -1.1% (SD = 5.7) in the placebo group at the distal radius (difference, -6.8%; 95% CI, -8.5 to -5.0; P <.0001) and -7.6% (SD = 5.9) in the exemestane group and -0.7% (4.9) in the placebo group at the distal tibia (difference, -6.9%; 95% CI, -8.4 to -5.5; P <.0001). Exemestane had a much more profound effect on cortical than trabecular bone.

Cheung and colleagues commented that their study cohort primarily included healthy, white, postmenopausal women with relatively normal areal BMD and adequate calcium and vitamin D intake. The findings may thus not be applicable to women with osteoporosis or breast cancer and women who are nonwhite.

On the positive side, their study is the first to examine the effect of an aromatase inhibitor on bone structure, and the largest placebo-controlled study to look at exemestane’s impact on bone density in healthy postmenopausal women.

The investigators said that their data underscore the importance of weighing the benefits and liabilities when deciding whether to prescribe exemestane for the primary prevention of breast cancer. However, they emphasized that more research is needed to determine exemestane’s effect on fracture risk.


Cheung AM, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial [published online ahead of print February 7, 2012]. Lancet. doi:10.1016/S1470-2045(11)70389-8.



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