Factors Associated With Worsening Menopause-Specific Health-Related Quality of Life and Treatment Discontinuation in a Breast Cancer Chemoprevention Trial
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Background: The Mammary Prevention.3 (MAP.3) randomized placebo-controlled trial evaluating exemestane for breast cancer prevention demonstrated a 65% relative reduction in invasive breast cancer incidence. Up to 50% of participants in both trial arms reported a clinically meaningful worsening in their menopause-specific health-related quality of life (HRQL). The incidence of both worsening HRQL and treatment discontinuation was highest within the first year post-randomization. Objectives: The objectives of the two manuscripts comprising this thesis were to 1) identify factors associated with worsening menopause-specific HRQL, and, 2) evaluate the association between clinically meaningful worsening in menopause-specific HRQL and early discontinuation of study treatment. Methods: The study sample was derived from the MAP.3 chemoprevention trial conducted by the NCIC Clinical Trials Group and consisted of 4,560 postmenopausal women at elevated risk for breast cancer. Menopause-specific HRQL was assessed prior to randomization, 6 months and annually thereafter using the Menopause-Specific Quality of Life Questionnaire (MENQOL). In Manuscript 1, Cox proportional hazards analysis was used to identify factors associated with a clinically meaningful worsening in domain-specific and overall menopause-specific HRQL. In Manuscript 2, multivariable log-binomial regression was used to assess the associations between a clinically meaningful worsening in menopause- specific HRQL, baseline participant characteristics and early treatment discontinuation. Results: Manuscript 1: Risk factors of worsening in overall menopause-specific HRQL included younger age, diagnoses of depression or anxiety, increasing medication burden and assignment to exemestane. Manuscript 2: The risk of early discontinuation was 77% higher among those experiencing a worsening in their overall menopause-specific HRQL (RR=1.77 95% CI: 1.51-2.08). Those who were current or past smokers, employed at baseline and were assigned to exemestane were also at increased risk for treatment discontinuation. Conclusions: Both treatment assignment and individual characteristics contributed to the worsening HRQL experiences observed in MAP.3, which may help inform the dialogue between clinicians and patients considering chemoprevention. A negative change in menopause-specific HRQL is an important risk factor of discontinuing chemoprevention therapy. The identification of individual-level factors associated with aromatase inhibitor discontinuation may assist physicians in appropriately monitoring and counseling their patients.