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Background: Arthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA)., Methods: We performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants., Results: Among 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00-2.20], had a more recent transition into menopause (<10 years) (5-10 years AOR 1.55, 95% CI 1.09-2.22; <5 years AOR 1.78, 95% CI 1.18-2.67), were within one year of starting AIs (AOR 1.61, 95% CI 1.08-2.40), and those who received chemotherapy (AOR 1.38, 95% CI 1.02-1.88) were significantly more likely to report AIAA. Additionally, SNP rs11648233 (HSD17B2) was significantly associated with higher odds of AIAA (AOR 2.21, 95% CI 1.55-3.16)., Conclusions: Time since menopause and start of AIs, prior chemotherapy, and SNP rs11648233 within the HSD17B2 gene in the estrogen pathway were significantly associated with patient-reported AIAA. These findings suggest that clinical and genetic factors involved in estrogen withdrawal increase the risk of AIAA in postmenopausal breast cancer survivors., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Arthralgia is common among women with breast cancer on adjuvant aromatase inhibitor (AI) therapy. Pain is associated with falls in the general population; however, little is known about the relationship between arthralgia and falls among AI users. Our objective was to determine whether joint pain severity and interference predict future falls., Methods: We conducted a prospective cohort study of postmenopausal women with stage I-III estrogen receptor-positive breast cancer who were prescribed a third-generation AI. Arthralgia symptoms were measured at baseline using a modified version of the Brief Pain Inventory. Fall occurrence was obtained at 24-month follow-up., Results: Among 667 participants (median age 63 years, interquartile range 57-69 years), 232 (35%, 95% CI 31 to 39%) reported falls 12-24 months after baseline. Among women who fell, 65 (28%) reported seeking medical assistance. After controlling for multiple fall risk factors, we found significant non-linear associations between baseline joint pain severity and risk of falls (p = 0.001). Women with joint pain severity scores ≥ 4 had a more than twofold increase in fall risk compared to those without pain (41% vs. 20%). We observed a similar relationship for pain interference and fall risk (p < 0.001). Fewer than half of participants reported having been asked about falls in the past 12 months by their primary care physician (44%) or oncologist (36%)., Conclusion: Joint pain increases the risk of falls among women with breast cancer on adjuvant AI therapy. Health care providers should evaluate and manage arthralgia symptoms and implement fall-prevention strategies for those who are at increased risk.

Objective: To evaluate the associations between polymorphisms in two genes, catechol-O-methyltransferase and T-cell leukemia/lymphoma 1 A, and acupuncture-mediated pain reduction among breast cancer survivors with aromatase inhibitor-associated arthralgia., Design, Setting, and Subjects: Biospecimens were obtained from 38 patients enrolled in a clinical trial of acupuncture for aromatase inhibitor-associated arthralgia in postmenopausal hormone receptor-positive breast cancer survivors., Methods: We used polymerase chain reaction to genotype the rs4680 (Val158Met) and rs4633 (His62His) variants in the catechol-O-methyltransferase gene and rs2369049 (A > G) and rs7158782 (A > G) variants in the T-cell leukemia/lymphoma 1 A gene. Response to acupuncture was defined by 30% reduction in end-of-treatment average pain, measured by the Brief Pain Inventory. We used Fisher exact tests to evaluate associations between genotype and treatment response., Results: Among participants, all six (15.8%) subjects who expressed AA in locus rs4680 responded to acupuncture. In a combined analysis, the 18 (47.4%) subjects with the responder genotype at either rs4680 (AA) or rs2369049 (GG or AG) were significantly more likely to respond to acupuncture than those without (77.8% vs 45.0%, P = 0.039)., Conclusions: Specific genetic variations at loci rs4680 and rs2369049 are associated with response to acupuncture-type intervention for management of arthralgia. These results serve as a proof of concept for applying a precision medicine framework to the study of cancer pain management.

Purpose: Fatigue is the most common and distressing symptom experienced by cancer survivors. This study sought to determine the prevalence and risk factors for fatigue among breast cancer (BC) survivors receiving aromatase inhibitors (AIs)., Material and Methods: We conducted a cross-sectional survey study among postmenopausal women with stage 0 to III BC receiving adjuvant AI therapy at the outpatient breast oncology clinic of a large university hospital. Participants with a score ≥4 on the 'worst fatigue' item of the Brief Fatigue Inventory were classified as having moderate or severe fatigue. Multivariate logistic regression analyses were performed to evaluate risk factors., Results: Among 1103 participants, 616 (55.8%) had moderate or severe fatigue. In the multivariate logistic regression model, women younger than 55 years were significantly more likely to report moderate to severe fatigue than women older than 65 years (adjusted odds ratio [AOR] = 1.58, 95% confidence interval [CI] = 1.07-2.35; p = 0.023). Compared to women with high school or less education, women with college or more education were significantly more likely to report moderate to severe fatigue (AOR = 1.40, 95% CI = 1.02-1.91; p = 0.037). Increasing body mass index (BMI) was significantly associated with increased risk of experiencing moderate to severe fatigue (overweight: AOR = 1.37, 95% CI = 1.01-1.84, p = 0.042; obesity: AOR = 2.08, 95% CI = 1.53-2.81, p < 0.001). Fatigue was significantly correlated with pain severity (r = 0.48, p < 0.001) and insomnia (r = 0.62, p < 0.001)., Conclusion: Moderate to severe fatigue complaints exceed 50% among AI users. Fatigue is highly related to younger age, higher education level, higher BMI, pain severity and insomnia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim of the Study: Breast cancer survivors who take aromatase inhibitors (AI) often suffer from chronic pain. Emerging evidence supports the use of acupuncture as an effective pain management strategy for this condition, but its acceptability among cancer survivors is unknown. We evaluated breast cancer survivors' preferences for acupuncture as compared with medication use and identified factors predictive of this preference., Methods: We conducted a cross-sectional study among breast cancer survivors who were currently, or had been, taking an AI. The primary outcome was degree of preference for acupuncture as compared with medication for pain management. We conducted multivariate logistic regression analyses to evaluate the effects of socioeconomic status (SES) factors and health beliefs on treatment preference., Results: Among 592 participants, 160 (27.0%) preferred acupuncture, 153 (25.8%) preferred medication and 279 (47.1%) had no clear preference. In a multivariate analysis that only included SES, higher education and white race were significantly associated with greater preference for acupuncture. When health beliefs were added, SES effects were attenuated, while greater expectation of acupuncture's effect, lower perceived barriers to its use, higher social norm (endorsement from family members and healthcare professionals) related to acupuncture and higher holistic health beliefs were associated with greater preference for acupuncture., Conclusion: We found similar rates of preference for acupuncture versus medication among breast cancer survivors for pain management. Specific attitudes and beliefs predicted such preferences, highlighting the importance of a patient-centred approach to align patient beliefs and preferences with therapeutic options for more effective pain management., Trial Registration Number: NCT01013337; Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Aromatase inhibitors (AIs) are a potentially life-saving treatment for breast cancer survivors, yet poor adherence to treatment is a prevalent problem. A common adverse effect of AI treatment is arthralgia, which is identified by survivors as a major reason for treatment discontinuation. Women who experience arthralgia on AIs often report feeling they have aged rapidly while on the treatment. In the present study, we examined whether arthralgia-associated ageing perceptions predicted non-adherence., Patients and Methods: We conducted a prospective cohort study among women with stage I-III breast cancer, who were on an AI and completed the Penn Arthralgia Aging Scale within 2 years of AI initiation. Adherence data were abstracted from medical charts by trained raters. Cox proportional hazard analysis was used to determine the relationship between ageing perceptions and time to non-adherence. All analyses included adjustments for joint pain severity., Results: Among 509 participants, 144 (28.3%) were non-adherent. As hypothesised, women with high levels of ageing perceptions were at greater risk of non-adherence than women with low levels of ageing perceptions (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.10-2.67; p = .02). High levels of depressive symptoms were also uniquely associated with increased risk of non-adherence (adjusted HR, 1.63; 95% CI, 1.03-2.59; p = .04)., Conclusion: Perceptions of ageing related to arthralgia and depressive symptoms predicted non-adherence to AIs. These findings suggest that interventions that address negative beliefs about ageing due to AI-related arthralgia and depressive mood can potentially improve rates of adherence to AIs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Although poor adherence to hormonal therapies such as aromatase inhibitors (AIs) is widely documented, to the authors' knowledge less is known regarding whether health beliefs predict treatment nonadherence. The objective of the current study was to evaluate the relationship between health beliefs (perceived susceptibility to breast cancer, perceived benefits of AI treatment, and perceived barriers to AI treatment) and adherence to AIs., Methods: Postmenopausal women with early-stage, estrogen receptor-positive breast cancer who were currently receiving treatment with an AI completed the 3-factor Health Beliefs and Medication Adherence in Breast Cancer scale and questionnaires concerning their demographics and symptoms. Adherence data (treatment gaps and premature discontinuation) were abstracted from participants' medical charts. Logistic regression analyses were conducted to evaluate the relationship between health beliefs and adherence., Results: Among 437 participants, 93 (21.3%) were nonadherent. Those who perceived greater barriers to their AI treatment were more likely to demonstrate AI nonadherence behaviors by the end of their treatment period compared with those who reported fewer barriers to AI therapy (adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.86 [P = .04]). In contrast, perceived susceptibility to cancer recurrence and perceived benefits of AIs did not appear to predict AI adherence. Minority individuals were found to have lower perceived susceptibility to breast cancer recurrence and higher perceived barriers to AI treatment (P<.05 for both)., Conclusions: Greater perceived barriers appeared to predict nonadherence to AIs. Interventions addressing women's negative beliefs regarding the challenges of AI treatment are needed to help optimize adherence in survivors of breast cancer. Cancer 2017;169-176. © 2016 American Cancer Society., Competing Interests: The authors declare that they have no conflict of interest. Moriah Brier, Dianne Chambless, Robert Gross, Jinbo Chen, and Jun Mao do not have conflicts of interest to report., (© 2016 American Cancer Society.)

Purpose: Poor adherence to oral adjuvant hormonal therapy for breast cancer is a common problem, but little is known about the relationship between self-report adherence measures and hormonal suppression. We evaluated the relationship of three self-report measures of medication adherence and oestrogen among patients on aromatase inhibitors (AIs)., Materials and Methods: We recruited 235 women with breast cancer who were prescribed AI therapy. Participants self-reported AI adherence by completing the following: (1) a single item asking whether they took an AI in the last month, (2) a modified Morisky Medication Adherence Scale-8 (MMAS-8) and (3) the Visual Analog Scale (VAS). Serum estrone and estradiol were analysed using organic solvent extraction and Celite column partition chromatography, followed by radioimmunoassay., Results: Ten percent of participants reported they had not taken an AI in the last month and among this group, median estrone (33.2 pg/ml [interquartile range (IQR)=22.3]) and estradiol levels (7.2 pg/mL [IQR=3.3]) were significantly higher than those in participants who reported AI use (median estrone=11.5 pg/mL [IQR=4.9]; median estradiol=3.4 pg/mL [IQR=2.1]; p<0.001). This relationship held when controlling for race and AI drug type., Conclusions: A single-item monthly-recall adherence measure for AIs was associated with oestrogen serum levels. This suggests that patient-reported monthly adherence may be a useful measure to identify early non-adherence behaviour and guide interventions to improve patient adherence to hormonal treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Breast cancer survivors on aromatase inhibitors often experience joint pain as a side effect of their treatment; qualitative investigations suggest that this arthralgia may cause women to feel that they are aging faster than they should be. To facilitate further study of this experience, the Penn Arthralgia Aging Scale (PAAS) was developed. This report describes the development and validation of the PAAS in a racially diverse sample of breast cancer survivors suffering from joint pain., Methods: The items of the scale were developed from a content analysis of interviews with patients. The scale was pilot-tested, and modifications were made on the basis of patient feedback. Subsequently, 596 breast cancer survivors who endorsed joint pain completed the 8-item PAAS. The factor structure (with exploratory factor analysis), the internal consistency, and the convergent, divergent, and incremental validity were examined., Results: The resulting scale had a 1-factor structure with strong internal consistency (Cronbach's α = .94) and demonstrated both convergent and divergent validity: the PAAS was significantly correlated with joint pain severity (rs = 0.55, P < .01) and had a small and nonsignificant correlation with actual age (rs  = -0.07, P = .10). The PAAS was also found to explain incremental variance in anxiety, depression, and pain interference outcomes., Conclusions: These findings suggest that the PAAS produces reliable and valid scores that capture perceptions of aging due to arthralgia among breast cancer survivors. With further research, the PAAS may advance our understanding of how perceptions of aging may affect breast cancer survivors' emotional, behavioral, and clinical outcomes., (© 2015 American Cancer Society.)

Introduction: Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs., Methods: Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations., Results: Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (β = 93.1; 95 % confidence interval (CI): 25.1-161.1; p = 0.008), eotaxin (β = 79.9; 95 % CI: 32.5-127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (β = 151.2; 95 % CI: 32.7-269.8; p = 0.013), and vitamin D-binding protein (VDBP) (β = 19,422; 95 % CI: 5500.5-33,344; p = 0.006)., Conclusions: Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.

Background: Although fatigue, sleep disturbance, depression, and anxiety are associated with pain in breast cancer patients, it is unknown whether acupuncture can decrease these comorbid symptoms in cancer patients with pain. The objective of this study was to evaluate the effect of electroacupuncture (EA) on fatigue, sleep, and psychological distress in breast cancer survivors who experience joint pain related to aromatase inhibitors (AIs)., Methods: The authors performed a randomized controlled trial of an 8-week course of EA compared with a waitlist control (WLC) group and a sham acupuncture (SA) group in postmenopausal women with breast cancer who self-reported joint pain attributable to AIs. Fatigue, sleep disturbance, anxiety, and depression were measured using the Brief Fatigue Inventory (BFI), the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). The effects of EA and SA versus WLC on these outcomes were evaluated using mixed-effects models., Results: Of the 67 randomly assigned patients, baseline pain interference was associated with fatigue (Pearson correlation coefficient [r]=0.75; P < .001), sleep disturbance (r=0.38; P=.0026), and depression (r=0.58; P < .001). Compared with the WLC condition, EA produced significant improvements in fatigue (P=.0095), anxiety (P=.044), and depression (P=.015) and a nonsignificant improvement in sleep disturbance (P=.058) during the 12-week intervention and follow-up period. In contrast, SA did not produce significant reductions in fatigue or anxiety symptoms but did produce a significant improvement in depression compared with the WLC condition (P=.0088)., Conclusions: Compared with usual care, EA produced significant improvements in fatigue, anxiety, and depression; whereas SA improved only depression in women experiencing AI-related arthralgia., (© 2014 American Cancer Society.)

Background: Arthralgia is a common and debilitating side-effect experienced by breast cancer patients receiving aromatase inhibitors (AIs) and often results in premature drug discontinuation., Methods: We conducted a randomised controlled trial of electro-acupuncture (EA) as compared to waitlist control (WLC) and sham acupuncture (SA) in postmenopausal women with breast cancer who self-reported arthralgia attributable to AIs. Acupuncturists performed 10 EA/SA treatments over 8 weeks using a manualised protocol with 2 Hz electro-stimulation delivered by a TENS unit. Acupuncturists administered SA using Streitberger (non-penetrating) needles at non-traditional acupuncture points without electro-stimulation. The primary end-point was pain severity by Brief Pain Inventory (BPI) between EA and WLC at Week 8; durability of response at Week 12 and comparison of EA to SA were secondary aims., Findings: Of the 67 randomly assigned patients, mean reduction in pain severity was greater in the EA group than in the WLC group at Week 8 (-2.2 versus -0.2, p=0.0004) and at Week 12 (-2.4 versus -0.2, p<0.0001). Pain-related interference measured by BPI also improved in the EA group compared to the WLC group at both Week 8 (-2.0 versus 0.2, p=0.0006) and Week 12 (-2.1 versus -0.1, p=0.0034). SA produced a magnitude of change in pain severity and pain-related interference at Week 8 (-2.3, -1.5 respectively) and Week 12 (-1.7, -1.3 respectively) similar to that of EA. Participants in both EA and SA groups reported few minor adverse events., Interpretations: Compared to usual care, EA produced clinically important and durable improvement in arthralgia related to AIs in breast cancer patients, and SA had a similar effect. Both EA and SA were safe., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Physical activity (PA) has numerous health benefits for breast cancer survivors. Recent data suggest that some breast cancer survivors treated with aromatase inhibitors may experience aromatase inhibitor associated musculoskeletal symptoms. It is unknown whether aromatase inhibitor associated musculoskeletal symptoms are associated with reduced PA and what other risk factors are associated with such PA reductions. We conducted a cross-sectional study at a large university-based breast cancer clinic among breast cancer survivors prescribed an aromatase inhibitor. At routine follow-up, we surveyed participants about aromatase inhibitor associated musculoskeletal symptoms, as well as pre-aromatase inhibitor, and current, PA levels. Among 300 participants, 90 (30%) reported a reduction of PA since the initiation of aromatase inhibitor therapy. Those with aromatase inhibitor associated musculoskeletal symptoms were more likely to report decreased PA (62% versus 38%, p = 0.001) compared with those without aromatase inhibitor associated musculoskeletal symptoms. In multivariate analyses, aromatase inhibitor associated musculoskeletal symptoms (odds ratio [OR] = 2.29 [95% confidence interval [CI]: 1.36-3.86]), and body mass index (OR = 1.06 [95% CI: 1.02-1.12]) were associated with reductions in PA. In subgroup analysis among breast cancer survivors with aromatase inhibitor associated musculoskeletal symptoms, self-reported lower extremity joint pain (OR = 1.23 [95% CI: 1.00-1.50]) and impaired lower extremity physical function (OR = 1.07 [95% CI: 1.01-1.14]) were associated with reductions in PA. Breast cancer survivors with aromatase inhibitor associated musculoskeletal symptoms were more likely to report reductions in PA since initiating aromatase inhibitor therapy compared with those without aromatase inhibitor associated musculoskeletal symptoms. Our findings suggest that tailored interventions targeting lower extremity functional limitations are needed to enable breast cancer survivors with aromatase inhibitor associated musculoskeletal symptoms to participate in PA., (© 2013 Wiley Periodicals, Inc.)

Background: Premature discontinuation of aromatase inhibitors (AIs) in breast cancer survivors compromises treatment outcomes. We aimed to evaluate whether patient-reported joint pain predicts premature discontinuation of AIs., Methods: We conducted a retrospective cohort study of postmenopausal women with breast cancer on AIs who had completed a survey about their symptom experience on AIs with specific measurements of joint pain. The primary outcome was premature discontinuation of AIs, defined as stopping the medication prior to the end of prescribed therapy. Multivariate Cox regression modeling was used to identify predictors of premature discontinuation., Results: Among 437 patients who met eligibility criteria, 47 (11%) prematurely discontinued AIs an average of 29 months after initiation of therapy. In multivariate analyses, patient-reported worst joint pain score of 4 or greater on the Brief Pain Inventory (BPI) (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.14-3.80, P = 0.016) and prior use of tamoxifen (HR 2.01, 95% CI 1.09-3.70, P = 0.026) were significant predictors of premature discontinuation of AIs. The most common reason for premature discontinuation was joint pain (57%) followed by other therapy-related side effects (30%). While providers documented joint pain in charts for 82% of patients with clinically important pain, no quantitative pain assessments were noted, and only 43% provided any plan for pain evaluation or management., Conclusion: Worst joint pain of 4 or greater on the BPI predicts premature discontinuation of AI therapy. Clinicians should monitor pain severity with quantitative assessments and provide timely management to promote optimal adherence to AIs.

Purpose: While patients often use the internet as a medium to search for and exchange health-related information, little is known about the extent to which patients use social media to discuss side effects related to medications. We aim to understand the frequency and content of side effects and associated adherence behaviors discussed by breast cancer patients related to using aromatase inhibitors (AIs), with particular emphasis on AI-related arthralgia., Methods: We performed a mixed methods study to examine content related to AI associated side effects posted by individuals on 12 message boards between 2002 and 2010. We quantitatively defined the frequency and association between side effects and AIs and identified common themes using content analysis. One thousand randomly selected messages related to arthralgia were coded by two independent raters., Results: Among 25 256 posts related to AIs, 4589 (18.2%) mentioned at least one side effect. Top-cited side effects on message boards related to AIs were joint/musculoskeletal pain (N = 5093), hot flashes (1498), osteoporosis (719), and weight gain (429). Among the authors posting messages who self-reported AI use, 12.8% mentioned discontinuing AIs, while another 28.1% mentioned switching AIs. Although patients often cited severe joint pain as the reason for discontinuing AIs, many also offered support and advice for coping with AI-associated arthralgia., Conclusion: Online discussion of AI-related side effects was common and often related to drug switching and discontinuation. Physicians should be aware of these discussions and guide patients to effectively manage side effects of drugs and promote optimal adherence., (Copyright © 2013 John Wiley & Sons, Ltd.)

Purpose: Insomnia is increasingly recognized as a major symptom outcome in breast cancer; however, little is known about its prevalence and risk factors among women receiving aromatase inhibitors (AIs), a standard treatment to increase disease-free survival among breast cancer patients., Methods: A cross-sectional survey study was conducted among postmenopausal women with stage 0-III breast cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic of a large university hospital. The insomnia severity index (ISI) was used as the primary outcome. Multivariate logistic regression analyses were performed to evaluate risk factors., Results: Among 413 participants, 130 (31.5 %) had subthreshold insomnia on the ISI, and 77 (18.64 %) exceeded the threshold for clinically significant insomnia. In a multivariate logistic regression model, clinically significant insomnia was independently associated with severe joint pain (adjusted odds ratio (AOR) 4.84, 95 % confidence interval (CI) 1.71-13.69, P = 0.003), mild/moderate hot flashes (AOR 2.28, 95 % CI 1.13-4.60, P = 0.02), severe hot flashes (AOR 2.29, 95 % CI 1.23-6.81, P = 0.015), anxiety (AOR 1.99, 95 % CI 1.08-3.65, P = 0.027), and depression (AOR 3.57, 95 % CI 1.48-8.52, P = 0.004). Age (>65 vs. <55 years; AOR 2.31; 95 % CI 1.11-4.81; P = 0.026) and time since breast cancer diagnosis (<2 vs. 2-5 years; AOR 1.94; 95 % CI 1.02-3.69; P = 0.045) were also found to be significant risk factors. Clinical insomnia was more common among those who used medication for treating insomnia and pain., Conclusions: Insomnia complaints exceed 50 % among AI users. Clinically significant insomnia is highly associated with joint pain, hot flashes, anxiety and depression, age, and time since diagnosis.

Introduction: Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA., Methods: We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders., Results: Among 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001)., Conclusions: Functional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA.

Hot flashes in breast cancer survivors (BCS) receiving adjuvant aromatase inhibitor (AI) therapy are common, but risk factors for these symptoms are ill-defined. This study tested if body size is associated with hot flashes in BCS on AI therapy. A cross-sectional study of postmenopausal BCS receiving adjuvant AI therapy was performed. The primary outcome was occurrence of patient-reported hot flashes. The primary exposures of interest were current body size and weight change since breast cancer diagnosis. Three hundred participants were enrolled at a mean age of 61 years (range 33-86) after an average AI exposure of 23 months (range 1 month-9 years). Fifty-nine percent reported hot flashes, 32% reported moderate to severe hot flashes, and 25% reported significant worsening of hot flashes since starting AI therapy. Sixty-one percent experienced weight maintenance (±10 lb), while 27% had weight gain (gained 10 lb or more), and 11% had weight loss (lost 10 lb or more). In multivariable analysis, weight gain was independently associated with hot flash occurrence (OR 2.1, 95% CI 1.1-4.4) and hot flash severity (OR 2.6, 95% CI 1.3-5.0) after adjusting for confounding. Current body size was not associated with hot flash occurrence, severity or change with AI therapy. In an outpatient BCS population on AI therapy, weight gain is a risk factor for hot flash occurrence. Women who gained at least 10 lb since breast cancer diagnosis were two times more likely to have hot flashes than women who maintained or lost weight. These results support the thermoregulatory model of hot flashes and argue against a protective effect of body fat in this population.

Background: Arthralgia is common in postmenopausal breast cancer survivors (BCS) who are receiving aromatase inhibitors (AIs). The objective of this study was to evaluate the perceived onset, characteristics, and risk factors for AI-related arthralgia (AIA)., Methods: In a cross-sectional survey of postmenopausal BCS who were receiving adjuvant AI therapy at a university-based oncology clinic, patient-reported attribution of AIs as a cause of joint pain was used as the primary outcome. Multivariate logistic regression analyses were performed to evaluate risk factors., Results: Among 300 survey respondents, 139 (47%) attributed AI as a cause of their current arthralgia. Of those patients, 74% recognized the onset of AIA within 3 months of starting medication, and 67% rated joint pain as moderate or severe in the previous 7 days. In multivariate logistic regression analyses, the time since last menstrual period (LMP) was the only significant predictor of AIA. Controlling for covariates, the women who had their LMP within 5 years had the highest probability of reporting AIA (73%), whereas those who had their LMP > or =10 years previously had the lowest probability of reporting AIA (35%; adjusted odds radio, 3.39; 95% confidence interval, 1.21-9.44; P = .02). Wrists/hands, ankles/feet, elbows, and knees appeared to be associated more strongly with AI-related symptoms than non-AI-related joint symptoms (all P < .01)., Conclusions: AIA was common, began within the first 3 months of therapy in most patients, and appeared to be related inversely to the length of time since cessation of menstrual function. These findings suggest that estrogen withdrawal may play a role in the mechanism of this disorder.

BackgroundArthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA).MethodsWe performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants.ResultsAmong 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00-2.20], had a more recent transition into menopause (

Background: Premature discontinuation of aromatase inhibitors (AIs) in breast cancer survivors compromises treatment outcomes. We aimed to evaluate whether patient-reported joint pain predicts premature discontinuation of AIs.Methods: We conducted a retrospective cohort study of postmenopausal women with breast cancer on AIs who had completed a survey about their symptom experience on AIs with specific measurements of joint pain. The primary outcome was premature discontinuation of AIs, defined as stopping the medication prior to the end of prescribed therapy. Multivariate Cox regression modeling was used to identify predictors of premature discontinuation.Results: Among 437 patients who met eligibility criteria, 47 (11%) prematurely discontinued AIs an average of 29 months after initiation of therapy. In multivariate analyses, patient-reported worst joint pain score of 4 or greater on the Brief Pain Inventory (BPI) (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.14-3.80, P = 0.016) and prior use of tamoxifen (HR 2.01, 95% CI 1.09-3.70, P = 0.026) were significant predictors of premature discontinuation of AIs. The most common reason for premature discontinuation was joint pain (57%) followed by other therapy-related side effects (30%). While providers documented joint pain in charts for 82% of patients with clinically important pain, no quantitative pain assessments were noted, and only 43% provided any plan for pain evaluation or management.Conclusion: Worst joint pain of 4 or greater on the BPI predicts premature discontinuation of AI therapy. Clinicians should monitor pain severity with quantitative assessments and provide timely management to promote optimal adherence to AIs. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer survivors (BCS) taking aromatase inhibitors (AIs) are at an increased risk for decreased bone density and fractures. Given the role vitamin D plays in bone metabolism, we examined the prevalence of and risk factors for vitamin D deficiency in a study of postmenopausal BCS on AIs. Methods: We collected data on 391 postmenopausal women with stage I-III breast cancer on AI therapy. Vitamin D levels were measured by radioimmunoassay from patients' sera; deficiency was defined as a level < 30 ng/mL. Multivariate models were created to assess risk factors for deficiency. Results: The median vitamin D level was 35 ng/mL (range 6.78-93.15), and 35% of women were vitamin D deficient. When adjusting for age and vitamin D supplementation, minority participants were more likely to be vitamin D deficient than white women, (adjusted odds ratio [AOR] 2.18, 95% confidence interval [CI]1.22-3.89, p=0.009). Both overweight (AOR 3.05, 95% CI 1.72-5.41, p<0.001) and obese participants (AOR 3.21, 95% CI 1.79-5.78, p<0.001) had higher deficiency rates than did normal weight participants. Conclusions: Hypovitaminosis D is common in BCS, and those who are nonwhite or overweight are at a higher risk of deficiency despite taking vitamin D supplements. [ABSTRACT FROM AUTHOR]