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Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer.

ABSTRACT: Aromatase inhibitors (AIs), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms occur in approximately half of treated women and lead to treatment discontinuation in 20 to 30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AI-associated musculoskeletal symptoms. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (P = .006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In addition, there was no association with either measure of pain sensitivity and change in patient-reported pain with AI therapy. AI-associated musculoskeletal symptoms are not likely due to decreased pain threshold or impaired CPM prior to treatment initiation, or to effects of estrogen depletion on pain sensitivity.This article presents our findings of the effect of estrogen deprivation on objective measures of pain sensitivity. In postmenopausal women, medication-induced estrogen depletion did not result in an identifiable change in pressure pain threshold or CPM. Impaired CPM may be associated with chemotherapy.

SUBMITTER: Henry NL

PROVIDER: S-EPMC4063362 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer.

Henry N Lynn NL Conlon Anna A Kidwell Kelley M KM Griffith Kent K Smerage Jeffrey B JB Schott Anne F AF Hayes Daniel F DF Williams David A DA Clauw Daniel J DJ Harte Steven E SE

The journal of pain 20140122 5

<h4>Unlabelled</h4>Aromatase inhibitors (AIs), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms occur in approximately half of treated women and lead to treatment discontinuation in 20 to 30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain as well as with impairment of descending pain inhibitory pathways, which may be a ...[more]

PMID: 24462504

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Project description:BackgroundEarly discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs.Patients and methodsPostmenopausal women with early-stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24 months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROs on AI discontinuation. Associations between biochemical factors and change in PROs were examined.ResultsA total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95% confidence interval (CI), 2.72-2.81; p = .015]; HR, 4.39 [95% CI, 2.40-8.02; p < .0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed.ConclusionChanges in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.Implications for practiceEarly changes in patient-reported outcomes (PROs) can predict nonpersistence to aromatase inhibitor therapy. If used in clinical practice, PROs might identify women at highest risk for early discontinuation and allow for interventions to improve tolerance before significant toxicities develop. Further research is needed to improve capturing PROs in routine clinical practice.

Project description:PurposeNonadherence to aromatase inhibitors (AIs) for breast cancer is common and increases the risk of recurrence. Text messaging increases adherence to medications for chronic conditions.MethodsWe conducted a randomized clinical trial of text messaging (TM) versus no text messaging (No-TM) at 40 sites in the United States. Eligible patients were postmenopausal women with early-stage breast cancer taking an AI for > 30 days with a planned duration of ≥ 36 months. Test messages were sent twice a week over 36 months. Content themes focused on overcoming barriers to medication adherence and included cues to action, statements related to medication efficacy, and reinforcements of the recommendation to take AIs. Both groups were assessed every 3 months. The primary outcome was time to adherence failure (AF), where AF was defined as urine AI metabolite assay results satisfying one of the following: < 10 ng/mL, undetectable, or no submitted specimen. A stratified log-rank test was conducted. Multiple sensitivity analyses were performed.ResultsIn total, 724 patients were registered between May 2012 and September 2013, among whom,702 patients (348 in the text-messaging arm and 354 in the no-text-messaging arm) were eligible at baseline. Observed adherence at 36 months was 55.5% for TM and 55.4% for No-TM. The primary analysis showed no difference in time to AF by arm (3-year AF: 81.9% TM v 85.6% No-TM; HR, 0.89 [95% CI, 0.76 to 1.05]; P = .18). Multiple time to AF sensitivity analyses showed similar nonsignificant results. Three-year self-reported time to AF (10.4% v 10.3%; HR, 1.16 [95% CI, 0.69 to 1.98]; P = .57) and site-reported time to AF (21.9% v 18.9%; HR, 1.31 [95% CI, 0.86 to 2.01]; P = .21) also did not differ by arm.ConclusionTo our knowledge, this was the first large, long-term, randomized trial of an intervention directed at improving AI adherence. We found high rates of AI AF. Twice-weekly text reminders did not improve adherence to AIs. Improving long-term adherence will likely require personalized and sustained behavioral interventions.

Dataset Information

Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer.

Publications

Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer.

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