PROJECT ABSTRACT
Although aromatase inhibitors (AIs) are the most effective therapy to increase disease-free survival in
postmenopausal women with estrogen receptor positive breast cancer, nearly half of patients receiving AIs
report debilitating musculoskeletal symptoms, such as joint pain and stiffness, as adverse effects. These
symptoms negatively impact patients' quality of life and cause poor adherence to and self-discontinuation of
medication, potentially resulting in higher rates of morbidity and mortality. Despite the frequent occurrence of
AI-associated musculoskeletal symptom (AIMSS), the mechanism(s) underlying development of AIMSS are
poorly understood, and many patients experience unremitting symptoms. Given that many chronic
musculoskeletal pain disorders are attributed to central pain dysregulation, the development of AIMSS may be
a consequence of central sensitization. While recent animal studies indicate that AI treatment is potentially
associated with both peripheral and central sensitization, to date, few investigators have focused on peripheral
and central sensitization in relation to the development and/or persistence of AIMSS in breast cancer survivors.
Therefore, the proposed F32 training award will address the following specific aims: 1. To evaluate the
feasibility by the (a) recruitment, (b) retention, (c) acceptability of subject burden, and (d) appropriateness of
dependent and independent variables; and, 2. To examine the underlying mechanisms by investigating (a) the
association of altered central pain processing with the presence and symptomatic severity of AIMSS and (b)
psychological and genetic contributions to AIMSS. To address these aims, in a prospective, longitudinal study
design, 40 participants will undergo the assessment of responses to well-controlled, experimental pain stimuli
(i.e. quantitative sensory testing [QST]) and clinical outcome measures of musculoskeletal symptoms and
psychological distress (e.g., coping strategy, pain vigilance, pain catastrophizing, anxiety), and the
determination of catechol-O-methyltransferase (COMT) variants using saliva samples prior to the AI therapy
(i.e. baseline) and at 3- and 6-months after initiating AI therapy. Results from this study will provide important
feasibility data for this ongoing program of research, addressing a significant and understudied health concern,
AIMSS, in women treated for breast cancer. The proposed investigation and training program will leverage the
dissertation work and contribute to my ongoing research and dissemination activities allowing for an ideal
training environment.