A randomized, placebo-controlled trial (NCIC CTG MAP.2) examining the effects of exemestane on mammographic breast density, bone density, markers of bone metabolism and serum lipid levels in postmenopausal women

Abstract

We hypothesized that exemestane (EXE) would reduce mammographic breast density and have unique effects on biomarkers of bone and lipid metabolism. Healthy postmenopausal women were randomized to EXE (25 mg daily) or placebo (PLAC) for 12 months and followed for a total of 24 months. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms and secondary endpoints were changes in serum lipid levels, bone biomarkers, and bone mineral density (BMD). Ninety-eight women were randomized (49 to EXE; 49 to PLAC) and 65 had PD data at baseline and 12 months. Among women treated with EXE, PD was not significantly changed from baseline at 6, 12, or 24 months and was not different from PLAC. EXE was associated with significant percentage increase from baseline in N-telopeptide at 12 months compared with PLAC. No differences in percent change from baseline in BMD (lumbar spine and femoral neck) were observed between EXE and PLAC at either 12 or 24 months. Patients on EXE had a significantly larger percent decrease in total cholesterol than in the PLAC arm at 6 months and in HDL cholesterol at 3, 6, and 12 months. No significant differences in percent change in LDL or triglycerides were noted at any time point between the two treatment arms. EXE administered for 1 year to healthy postmenopausal women did not result in significant changes in mammographic density. A reversible increase in the bone resorption marker N-telopeptide without significant change in bone specific alkaline phosphatase or BMD during the 12 months treatment period and 1 year later was noted. Changes in lipid parameters on this trial were modest and reversible.

Breast MRI Fibroglandular Volume and Parenchymal Enhancement in BRCA1 and BRCA2 Mutation Carriers Before and Immediately After Risk-Reducing Salpingo-Oophorectomy

“…The data regarding change in mammographic breast density in patients taking aromatase inhibitors are mixed. Two studies reported a significant decrease in mammographic breast density in women taking aromatase inhibitors [19,20], whereas randomized placebocontrolled trials of two different aromatase inhibitors found no difference in mammographic breast density at 6, 12, or 24 months compared with baseline [21,22]. Longer follow-up may be needed to assess the change in fibroglandular volume over time, including in our study, because our post-RRSO MRI median time was only 8 months.…”

Clinical and epidemiological issues in mammographic density

“…55 A randomized study of another aromatase inhibitor, exemestane, versus placebo similarly found no significant change in percent density with treatment. 56 Endogenous sex hormones Studies aimed at testing the hypothesis that in postmenopausal women breast density reflects blood levels of sex hormones, found no association after BMI had been taken into account (women with high BMI have higher hormone levels and lower density levels). [57][58][59] In addition, the lack of association between density of the surrounding breast tissue and estrogen receptor (ER) status in breast cancer supports the hypothesis that density and postmenopausal endogenous estrogen levels are indepen dent risk factors.…”

Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: A Dutch TEAM trial analysis

“…decreasing breast density [14][15][16][17][18][19]. although much less data are available about the prognostic significance of decreasing breast density by ais as compared this data of tamoxifen.…”

“…The effects of ais on breast density in postmenopausal early breast cancer patients have mainly been investigated during or after treatment with the non-steroidal ais anastrozole and letrozole [14][15][16][17][18][19]. Data on the effect of the steroidal ai exemestane on breast density are limited.…”