Aromatase inhibitors (AIs) are the first-line treatment in women with
breast cancer for total
estrogen depletion. Half the treated women may develop
pain, and this condition may therefore be seen as a clinical model of
pain related to
estrogen deprivation. In this prospective multicenter study, we classified AI-related
pain syndromes and identified their predictors. A 1-year, prospective, multicenter cohort study, with 6 visits, was carried out on 135 women with early-stage
breast cancer and no
pain at the start of AI treatment. At initial assessment, we investigated clinical (demographic and psychosocial,
cancer characteristics and treatment, sleep, quality of life), biological (
sex hormones,
vitamin D, bone
biomarkers, oxidative stress, immunologic and inflammatory markers), environmental, and genetic (polymorphism for
pain mechanisms) risk factors for
pain. During 1 year of follow-up, 77 women (57%) developed
pain, leading to AI discontinuation in 12 cases. Five
pain syndromes were identified:
joint pain (36%), diffuse
pain (22%),
tendinitis (22%),
neuropathic pain (9%), and mixed
pain (11%), which are mostly persistent (57%), with diffuse and
joint pains the most intense. Risk factors for the development of
pain included higher levels of anxiety and impaired quality of life at the initial assessment, whereas
cancer characteristics, genetic background,
inflammation, and immunologic and hormonal status at baseline were not significant predictors.
PERSPECTIVE: This article presents a classification of AI-related
pain syndromes induced by
estrogen deprivation that were previously described as
arthralgia, but not as neuropathic, diffuse, and mixed
pain. This
estrogen deprivation-related condition represents a clinical model of
pain, and our study identified mostly psychological risk factors for
pain development.