Effect of exemestane on bone mineral density in postmenopausal women at increased risk for breast cancer

Abstract #5086 Background: The aromatase inhibitors (AIs) show promise for breast cancer prevention in postmenopausal women. However these agents have been shown to decrease bone mineral density in women with breast cancer. Exemestane, a steroidal aromatase inhibitor, may be more bone sparing than the non-steroidal aromatase inhibitors. Methods: We conducted a phase II trial of exemestane in postmenopausal women at increased risk of breast cancer to assess the effect on anterior-posterior (AP) spine and total hip bone mineral density (BMD). Eligible participants are at increased risk for breast cancer by virtue of: Gail model risk > 1.7% over 5 years; high risk pathological lesion (e.g. lobular neoplasia, ductal carcinoma in situ); known BRCA1/2 deleterious mutation or prior stage I/II breast cancer at least 2 years from breast cancer treatment and not treated with AIs. Women were required to undergo DEXA scan of the AP spine and hip at baseline and were excluded if AP spine T-score was ≤-2.5. AP spine measurements were done twice at each time point and the results averaged. Study participants receive exemestane 25 mg, calcium carbonate 1200 mg and vitamin D 400 IU daily for two years. We report the results of a planned interim safety analysis assessing one year change in bone density in the first 18 subjects. Student's t-test was used to determine relative change from baseline in AP spine and total hip BMD. Results: To date, 30 women have enrolled in the trial and 21 have completed 1 year of exemestane. Three women discontinued agent after an average of 3 months due to joint pain. For the 21 included in this analysis 15 were eligible due to a high risk pathological lesion, 4 by Gail Model and 2 by prior breast cancers. The average change in AP spine BMD from baseline to 1 year (N= 21) is –1.3 %, range -10.0 to +7.0% (p=0.20 for the null hypothesis of zero overall change; 95% C.I. for the mean -3.2% to +0.7%). Average AP spine T score is -0.28 at baseline and -0.45 at one year. Change in total hip BMD is -1.4%, range -7.5% to 5.9% (p=0.058, 95% C.I. -2.8% to +0.1%). Average total hip T score is -0.05 at baseline and -0.17 at one year. Conclusions: These preliminary data suggest that exemestane 25 mg/day for one year with concurrent calcium and vitamin D has acceptable effects on bone density in postmenopausal high risk women, although there were wide ranges in effects. The observed average reduction in BMD is less than the reported effect in treatment s