Quality of Life in MAP.3 (Mammary Prevention 3): A Randomized, Placebo-Controlled Trial Evaluating Exemestane for Prevention of Breast Cancer

Abstract

Purpose Exemestane, a steroidal aromatase inhibitor, reduced invasive breast cancer incidence by 65% among 4,560 postmenopausal women randomly assigned to exemestane (25 mg per day) compared with placebo in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MAP.3 (Mammary Prevention 3) trial, but effects on quality of life (QOL) were not fully described. Patients and Methods Menopause-specific and health-related QOL were assessed by using the four Menopause-Specific Quality of Life Questionnaire (MENQOL) domains and the eight Medical Outcomes Study Short Form Health Survey (SF-36) scales at baseline, 6 months, and yearly thereafter. MENQOL questionnaire completion was high (88% to 98%) in both groups at each follow-up visit. Change scores for each MENQOL and SF-36 scale, calculated at each assessment time relative to baseline, were compared by using the Wilcoxon rank-sum test. Clinically important worsened QOL was defined as a MENQOL change score increase of more than 0.5 (of 8) points and an SF-36 change score decrease of more than 5 (of 100) points from baseline. Results Exemestane had small negative effects on women's self-reported vasomotor symptoms, sexual symptoms, and pain, which occurred mainly in the first 6 months to 2 years after random assignment. However, these changes represented only a small excess number of women being given exemestane with clinically important worsening of QOL at one time or another; specifically, 8% more in the vasomotor domain and 4% more each in the sexual domain and for pain. No other between-group differences were observed. Overall, slightly more women in the exemestane arm (32%) than in the placebo arm (28%) discontinued assigned treatment. Conclusion Exemestane given for prevention has limited negative impact on menopause-specific and health-related QOL in healthy postmenopausal women at risk for breast cancer.

A Randomized, Placebo-Controlled, Phase II, Presurgical Biomarker Trial of Celecoxib Versus Exemestane in Postmenopausal Breast Cancer Patients

“…In the MAP-3 prevention trial, exemestane did not affect quality of life and did not increase fracture risk compared with placebo, notwithstanding a reduction in bone mineral density (8,49,54). In the CAAN trial (49), exemestane in combination with celecoxib showed a significantly better quality of life compared with exemestane alone or letrozole.…”

Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years

“…Both questionnaires have been shown to be valid, reliable, and responsive to change in the target population 3,5,6 and were used in the MA.17 trial. 7 To compare QOL with the general population, we used data from the CCTG chemoprevention trial Mammary Prevention 3 (MAP.3; which used the SF-36 and the MENQOL) 8 and also from a Canadian population-based survey that used the SF-36. 9 …”

Primary chemoprevention of breast cancer: Are the adverse effects too burdensome?

“…In a recent placebo-controlled RCT of exemestane, the drug was associated with worse vasomotor symptoms, bodily pain and sexual domain scores. 12 In another RCT, anastrozole was found to increase the risk of musculoskeletal effects, hypertension, vaginal dryness and vasomotor symptoms. 13 Both aromatase inhibitors worsened bone mineral density.…”

“…13 Both aromatase inhibitors worsened bone mineral density. 12,13 Because of such adverse effects, 25%-40% of trial participants stopped using the chemoprevention drugs. 6 Discontinuation of drug use among the wellselected patients in clinical trials likely underestimates noncompliance in general clinical settings.…”