Aromatase Inhibitors Users Research Articles

Prospective study to assess fluid accumulation and tenosynovial changes in the aromatase inhibitor-induced musculoskeletal syndrome: 2-year follow-up data

Aromatase inhibitors (AIs) frequently lead to the AI-induced musculoskeletal syndrome (AIMSS). Looking into its pathophysiology, 6 months of AI therapy thickens the tendon sheath with intra-articular fluid (IAF) retention and loss of grip strength. We here report 24-month follow-up data. A prospective cohort study of 33 postmenopausal breast cancer patients received adjuvant endocrine therapy; 27 received an AI and 6 received tamoxifen. At baseline, 6 and 24 months patients had a rheumatologic examination, including a grip strength test, and magnetic resonance imaging of both hands and wrists. The primary end point was tenosynovial changes; secondary end points were changes in morning stiffness, grip strength and IAF. Twenty-three AI and 5 tamoxifen patients completed all investigations. Between month 6 and 24, IAF further increased in AI users (P = 0.04) but not in tamoxifen users, and grip strength further decreased in both groups. The worsened tenosynovial changes were strongly correlated with a decrease in grip strength. At 24 months, morning stiffness continued to be present in over a third of AI users. AIMSS represents a substantial problem in breast cancer patients. It is associated with tenosynovial changes, IAF retention, joint stiffness and loss of grip strength that do not improve with prolonged use.

Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004–2010

Nearly a decade ago, researchers identified a potential interaction between tamoxifen and strong CYP2D6 inhibitors, including several frequently used antidepressants. Based on evidence available at that time, a United States Food and Drug Administration advisory committee recommended tamoxifen's label be changed in October 2006, noting that postmenopausal women with estrogen receptor-positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug interactions may be at increased risk of cancer recurrence. The impact of accumulating drug risk information on antidepressant use is unknown. We conducted a retrospective, longitudinal cohort study of 13,205 women aged 50-95 with breast cancer initiating tamoxifen between July 2004 and December 2009. We evaluated trends in strong, moderate, and weak CYP2D6-inhibitor antidepressants and tamoxifen co-prescribing and factors associated with ongoing strong inhibitor use. A propensity score matched control group (aromatase inhibitor initiators) was used to estimate changes in co-prescribing, accounting for secular trends. In each month, approximately 24 % of tamoxifen and aromatase inhibitor users were prescribed antidepressants. Among women using tamoxifen and antidepressants, 34 % used strong inhibitors between 2004 and 2006 versus 15 % in 2010. Strong inhibitor use decreased more among tamoxifen users than aromatase inhibitor users (difference-in-differences [DD] -0.09; 95 % confidence interval [CI] -0.15, -0.03). Weak inhibitor use increased among tamoxifen users from 32 % between 2004 and 2006 to 52 % in 2010, more rapidly than among aromatase inhibitor users (DD 0.15; CI 0.08, 0.23). The factor most strongly associated with strong inhibitor and tamoxifen co-prescribing after 2006 was prior strong inhibitor use (RR 4.73; CI 3.62-6.18). In conclusion, there were substantial declines in strong CYP2D6-inhibitor use among tamoxifen users following dissemination of information suggesting a potential for increased risk with co-prescribing. Whether patients and providers will continue to avoid strong inhibitor antidepressants is yet to be seen, but clinicians appear to be responsive to drug interaction risk information in this setting.

Dry eye syndrome in aromatase inhibitor users

Aromatase inhibitors are frequently used as an adjuvant therapy in the treatment of breast cancer. We observed that several patients taking aromatase inhibitors presented with severe dry eye symptoms, and we investigated whether there is a relationship between aromatase inhibitors and dry eyes in these patients. Retrospective chart review. Forty-one women. A computerized search of health records was performed to identify patients using anastrazole, letrozole and exemestane seen by the Cornea Service from August 2008 to March 2011. The results were compared with age-matched controls. Ocular surface changes among aromatase inhibitors users. Of the 41 women, 39 were Caucasians. Thirty-nine patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one had an unknown primary cancer. Mean age was 68 ± 11.3 years (range 47-95). Most common presenting symptoms were blurred vision in 28 (68%) patients, irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%) patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients. Mean Schirmer's test measurement was 11 ± 5.8 mm (range 0.5-20 mm). Blepharitis was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome was found in only 9.5% of patients. Because the prevalence of ocular surface disease signs and symptoms appears to be higher in study group than control patients, aromatase inhibitors might be a contributing factor to the dry eye symptoms.

Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors

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. 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. 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. 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.

Linkage of routinely collected oncology clinical data with health insurance claims data—an example with aromatase inhibitors, tamoxifen, and all‐cause mortality

Studies of cancer based solely on health insurance claims data typically lack information on cancer clinical characteristics that are strong predictors of treatment and prognosis. Our objective was to evaluate routinely collected cancer clinical data for adjustment of confounding using an example evaluation of mortality associated with aromatase inhibitors and tamoxifen. This cohort study identified women with breast cancer from 2008 through 2010 using health insurance claims data linked to clinical information on stage at diagnosis, current clinical status, histology, and other clinical markers. Estimated mortality rates (MRs) and 95% confidence intervals (CI) were compared between users of aromatase inhibitors or tamoxifen, adjusted for claims-identified covariates and additionally for the clinical variables using propensity scores and proportional hazards regression models. The overall (n = 7974) estimated MR was 69/1000 person-years (95%CI = 62-76 person-years), 308/1000 person-years (95% CI = 273-345 person-years) for women with metastasis, and 12/1000 person-years (95%CI = 8-16 person-years) for women without active cancer. Propensity score matching of aromatase inhibitor users (n = 777) with tamoxifen users (n = 535) removed many, but not all, covariate imbalances. The hazard ratios (HRs) of all-cause mortality comparing users of aromatase inhibitors with tamoxifen users ranged from 1.0 to 1.6, with the HR most similar to previous clinical trials (0.87) coming from the claims-only analysis. We were able to address potential unmeasured confounders by linking clinical information to the claims data; however, there was no apparent improvement in confounding control in the chosen example. Conditioning eligibility on the clinical data restricted the sample size substantially.

The CIRAS study: a case control study to define the clinical, immunologic, and radiographic features of aromatase inhibitor-induced musculoskeletal symptoms

Aromatase inhibitors (AIs) are widely prescribed for post-menopausal hormone receptor-positive breast cancer; however, musculoskeletal symptoms limit their tolerability. The purpose of this study was to determine whether joint pain in women receiving AIs is associated with inflammatory arthritis as measured by the disease activity score-28 (DAS-28), and to evaluate association with tenosynovitis on ultrasound. A total of 48 postmenopausal women with stage I-III breast cancer and hand pain were recruited from the Lombardi Comprehensive Cancer Center. Those receiving AIs were cases (n = 25), and those not receiving AIs were controls (n = 23). During a single study visit, subjects underwent blinded rheumatologic evaluation, DAS-28, health assessment questionnaires, autoantibodies, inflammatory markers, hand X-ray, and hand Duplex ultrasound. There were no significant differences between cases and controls in DAS-28, or inflammatory markers. A positive ANA (titer > 1:160) was found in ten patients, four of whom met criteria for autoimmune disease (two with rheumatoid arthritis and two with Sjogren's syndrome, equally distributed among cases and controls). This highlights the importance of considering underlying autoimmune disease in subjects with musculoskeletal complaints. Morning stiffness was more prolonged in women receiving AIs, but this did not reach statistical significance (P = 0.07). Ultrasound evidence of flexor tenosynovitis was common in both groups. Although tenosynovitis was not correlated with AI use (P = 0.26), there was a trend toward an association between tenosynovitis and morning stiffness (P = 0.089). While aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) were more common in subjects receiving AIs, they were not unique to AI users. There was no association between presence of AIMSS features and other chemotherapy or medication exposures. Although the majority of subjects had been using AIs for more than 6 months, this study did not find evidence for inflammatory arthritis in women with hand pain receiving AIs. Further studies are needed to develop a case definition of AIMSS, and to confirm whether these symptoms are attributable to AI use.

Association between tamoxifen treatment and diabetes

There is increasing evidence linking breast cancer and diabetes; however, few studies have explored the association between cancer treatments and risk of diabetes. Tamoxifen may increase diabetes incidence through its estrogen-inhibiting effects. This study assessed whether tamoxifen treatment in older breast cancer survivors is associated with an increased risk of diabetes. This nested case-control study used population-based health databases in Ontario, Canada to identify women older than 65 years with early stage breast cancer between April 1, 1996 and March 31, 2006. Cases were defined as cohort members diagnosed with diabetes during follow-up (March 31, 2008), and each case was age-matched with up to 5 controls who did not develop diabetes. After adjusting for other risk factors, the authors compared the likelihood of diabetes between current tamoxifen users and tamoxifen nonusers, based on prescriptions at diabetes diagnosis. They also compared diabetes risk in current aromatase inhibitor users versus nonusers. Of 14,360 breast cancer survivors identified, mean age 74.9 years, 1445 (10%) developed diabetes over a mean follow-up of 5.2 years. Current tamoxifen therapy was associated with a significantly higher risk of diabetes compared with no tamoxifen therapy (adjusted odds ratio, 1.24; 95% confidence interval, 1.08-1.42; P = .002). There was no association between aromatase inhibitor therapy and diabetes. Current tamoxifen therapy is associated with an increased incidence of diabetes in older breast cancer survivors. These findings suggest that tamoxifen treatment may exacerbate an underlying risk of diabetes in susceptible women; further studies are needed to better explore this association.

An analysis of vitamin D (Vit D) and serum estrogens in postmenopausal (PM) breast cancer (BC) patients receiving aromatase inhibitors (AIs).

596 Background: Vit D supplementation is common in BC. Given reports that Vit D modulates aromatase activity, we examined the relationship between Vit D and estrogen levels in PM BC. Methods: 125 PM women within 2 years of diagnosis of T1-3, N0-3, M0 BC were recruited in Toronto and Los Angeles between Mar 2009 and Jan 2010. Data included: anthropometrics (measured); medications and Vit D supplementation (structured interview); and tumor/treatment variables (clinical records). Serum was analyzed for 25(OH)D by radioimmunoassay (RIA) and estradiol (E2) and estrone (E1) by extraction-column chromatography-RIA. Statistical analyses used t-tests, Pearson correlation (r) and regression models after suitable transformation of variables. Results: Hormone therapies included AIs (n=56), tamoxifen (n=30) and none (n=39). The tamoxifen and no hormone groups did not differ for important variables, and were combined (non-AI, n=69). Mean age was 62 years, BMI 27 kg/m2, Vit D supplementation 1244 IU/day, 25(OH)D 98 nmol/L; these attributes were similar in AI users and non-users. Mean E2 and E1 levels (pmol/L) were significantly lower in AI users (19.9 and 26.2) than non-users (39.6 and 123.7), both p<0.0001. The relationship between 25(OH)D and E2 differed qualitatively in AI users vs non-users (interaction p = 0.002): in AI users, 25(OH)D was positively correlated with E2 (r = + 0.31, p=0.02); in non-AI users this correlation was negative (r = − 0.26, p=0.03). 25(OH)D was not associated with E1 in either group. BMI was not associated with either E1 or E2 in AI-users (r = +0.09, p=0.52; r = − 0.03, p=0.84), but was univariably associated with E1 but not E2 in non-AI users (r = +0.44, p=0.0001, and r = +0.22, p=0.07). In multivariable analyses [age, BMI, 25(OH)D], 25(OH)D was positively associated with E2 in AI users (p=0.04) and negatively in non-AI users (p=0.05). BMI was associated with E1 in non-AI users (p=0.002). Measurement of AI levels is underway. Conclusions: In PM BC survivors, serum 25(OH)D was associated with higher E2 among AI users but not non-AI users. If replicated, this finding has implications for BC survivors receiving AIs. Funded by the Breast Cancer Research Foundation.

A population-based assessment of the risk of fragility fracture associated with the use of adjuvant hormone therapy for early breast cancer in older women.

519 Background: Change in bone density is one of the most commonly reported long-term sequelae of adjuvant hormonal therapy for the treatment of early breast cancer (EBC), although the magnitude and direction of change varies with the type of hormonal therapy. Compared with tamoxifen (TAM), the use of aromatase inhibitors (AI) has been associated with an increased risk of fragility fracture, but it remains unclear how much of this increased risk is attributable to the protective effect of TAM versus the detrimental effects of the AIs. We sought to determine the population based risk of fragility fracture associated with the use of adjuvant hormonal therapy using linked administrative databases in older women with EBC compared with non-cancer controls. Methods: All incident EBC patients >66y diagnosed between Jan/01-Dec/08 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to multiple provincial healthcare databases to provide comprehensive medical follow-up. Two treatment cohorts were identified based on the use of either TAM (5,704) or AI (4,760). Using a propensity score matching method, a non-cancer control group was created for both the TAM (n = 16,322) and AI (n = 13, 063) cohorts. Cox proportional hazard models were used to determine the association between each hormone therapy and the development of a fragility fracture. Results: After a median observation time of 5.1 years for TAM, and 2.8 years for AI, 11.5% of the TAM and 7.5% of the AI users developed a fragility fracture. Compared with matched controls (Table), TAM users had a significantly lower adjusted risk of fracture, while AI users had a higher risk. Conclusions: Fragility fractures are a concern in older women with EBC on adjuvant hormone therapy, and bone health should be monitored closely, particularly with the use of AIs. Hazard ratio (HR) for fragility fracture associated with hormone therapy for EBC. Group N Fragility fractures (%) HR 95% CI P value Tam 5,704 647 (11.5%) 0.91 0.83–0.99 0.03 Tam non-cancer control 16,322 2,115 (13.0%) 1.00 AI 4,760 356 (7.5%) 1.12 0.99–1.26 0.07 AI non-cancer control 13,063 963 (7.3%) 1.00

Fracture risk and adjuvant hormonal therapy among a population-based cohort of older female breast cancer patients

The risk of hip and other fractures was examined among a population-based group of older women with breast cancer. Women using aromatase inhibitors (AIs) were found to be over three times more likely to have a hip fracture over approximately 3years' follow-up. Other fracture risk factors were also identified. Aromatase inhibitors have been shown in randomized trials to increase total fracture risk compared with tamoxifen, but the fracture risks in the trials were relatively low, and no difference in hip fracture has been demonstrated. A population-based cohort of 2003 breast cancer survivors ≥65 were followed prospectively for a median of 36months. Patient survey information regarding adjuvant breast cancer therapies, prescription osteoporosis treatments, and other factors potentially associated with fracture was supplemented with cancer registry information. Hip and total nonvertebral fractures were determined using a validated Medicare algorithm, and the association of these fractures with adjuvant hormonal therapies was examined using Cox models. The cohort of 2,748 women with a mean age of 72.8 (SD 5.4) included 28.2% who took an aromatase inhibitor and 27.8% tamoxifen. There were 41 hip fractures (1.5%) and 218 nonvertebral fractures (7.9%) among the cohort. Subjects using AIs (adjusted hazard ratio 3.24 (1.05, 9.98)) and subjects not using hormone therapy (3.32 (1.14, 9.65)) were more likely than users of tamoxifen to have a hip fracture. Bisphosphonate use was more common among AI users but did not explain these results. Users of AIs were more likely to have nonvertebral fractures, but this result did not reach statistical significance (adjusted hazard 1.34 (0.92, 1.94)). Hip and other fractures were common in an older population-based cohort of breast cancer survivors, and aromatase inhibitor use was associated with an increase in the short-term risk of hip fractures not detected in randomized controlled trials.

Abstract B4: Impact of obesity on the effectiveness of aromatase inhibitors (AIs): Can breast cancer survivors on AIs lose weight compared to non-AI users?

Abstract Background and Objectives: Weight at diagnosis and weight gain after diagnosis are associated with increased risk of breast cancer (BrCa) recurrence and mortality. In addition, post-menopausal obese breast cancer survivors on anti-hormonal therapy were 40% more likely to develop a local recurrence and 46% more likely to develop a distant recurrence compared to their normal weight counterparts. This evaluation was conducted to examine if a diet/exercise/behavioral weight loss intervention for overweight breast cancer survivors: 1) would impact BrCa risk biomarkers and 2) would the response differ by aromatase inhibitor (AI) status. Methods: 84 BrCa survivors with a BMI 25-45 kg/m,2 ≥3 months from chemotherapy were recruited, and 52 agreed to participate. 6 (11%) participants did not complete the intervention. The 6-month intervention included: 225 minutes/week of aerobic exercise, resistance training, 1200-1500 calorie/day diet, and weekly group behavioral meetings. Pre and postintervention assessments included: anthropometrics (weight, BMI), body composition (DEXA % body fat), and serum biomarkers (estradiol, testosterone, SHBG, IGF-1/IGFBP3, insulin, leptin, adiponectin, glucose, CRP, cholesterol). Results are shown for 52 women (median age 52 ± 8 years) who initiated the program and 45 (87%) who completed the 6-month intervention. Results: Women were approximately 4.25 years from diagnosis, their median weight at diagnosis was 84.1 kg (±15.8), and BMI was 31.3 kg/m2 (±5.6). Median pre-intervention weight was 91.8 kg (±13.4) and participants lost an average of 10.6 kg (±6.0)* or 13.3% (±28.8)* of their starting weight after the 6-month intervention. BMI decreased from 32.6 kg/m2 (±4.7) to 28.2 kg/m2 (±4.7)* and total percent body fat decreased by 5.6% (±4.5)*. Favorable changes in serum biomarkers of BrCa risk were observed for insulin*, leptin*, adiponectin*, and estradiol*. When comparing AI users to nonusers the significant favorable change in estradiol was not seen for those on AI's. There was a significant difference in decrease in % body fat* between AI users and nonusers. No other differences were significant. (*p-values &amp;lt;0.05) Conclusions: Overall, results suggest a 6-month diet/exercise/behavioral weight loss intervention in overweight post-menopausal BrCa survivors results in a significant decrease in weight and change in serum biomarkers of BrCa risk in both current AI users and nonusers, however, due to the small sample size significant between group difference were not seen. Larger studies evaluating the effects of weight and weight loss based on exposure to antihormonal therapy are needed. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B4.

The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer

Aromatase inhibitors (AIs) have become the standard adjuvant therapy of postmenopausal breast cancer survivors. AIs induce a reduction of bioavailable estrogens by inhibiting aromatase, which would be expected to induce alterations in body composition, more extensive than induced by menopause. The objectives are to examine the impact of AIs on (1) DXA-scan derived body composition and (2) gonadal hormone levels. This is a sub-analysis of a 2-year double-blind, placebo-controlled, randomized trial of 82 women with nonmetastatic breast cancer, newly menopausal following chemotherapy, who were randomized to risedronate (35 mg once weekly) versus placebo, and stratified for their usage of AI versus no AI. Outcomes included DXA-scan derived body composition and gonadal hormone levels. As a group, total body mass increased in women over 24 months. Women on AIs gained a significant amount of lean body mass compared to baseline as well as to no-AI users (P < 0.05). Women not on an AI gained total body fat compared to baseline and AI users (P < 0.05). Free testosterone significantly increased and sex hormone binding globulin (SHBG) significantly decreased in women on AIs compared to no AIs at 24 months (P < 0.01) while total estradiol and testosterone levels remained stable. Independent of AI usage, chemotherapy-induced postmenopausal breast cancer patients demonstrated an increase of total body mass. AI users demonstrated maintenance of total body fat, an increase in lean body mass and free testosterone levels, and a decrease in SHBG levels compared to no-AI users. The mechanisms and implications of these changes need to be studied further.

Translational cell study exploring the role of estrogen receptor β expression as a predictive and/or prognostic factor in breast cancer patients

e22185 Background: We have reported that positive expression of Estrogen receptor β (ERβ) was associated with better prognosis in the early breast cancer patients treated with adjuvant tamoxifen monotherapy (J Clin Oncol. 2008). In addition, this was also true in the ERα-negative/PR-negative/Her-2 negative patients. We explored the biological impact of ERβ in breast cancer cell lines to determine whether these observations were due to its prognostic power or predictive power of response to the therapy. Methods: Since MCF-7 cell was ERβ-negative ERα-positive cell line, we established two stable clones of MCF-7 by introducing ERβ expression vector (β-clone 1, β-clone 2) as the model of ERβ-positive ERα-positive breast cancer. MDA-MB 231 cell was used as ERβ-positive triple-negative cell line. These cells were subjected to proliferation, expression and functional analysis. Results: In western blotting, both β-clone 1 and clone 2 showed decreased expression of PR and Her-2 than parent MCF-7, although there were no differences in ERα expression. Expression of ERβ decreased estradiol (E2) induced proliferation ability and rate of cells in S-phase cycle. PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) did not show any difference in response, and IC 50 for 4 OH-tamoxifen and fulvestrant did not differ among MCF-7, β-clone 1 and clone 2 (0.05–0.1 μM). Whereas, cell death due to deprivation of E2 from 1nM to 1pM was more frequently observed in ERβ-expressing clones than in parent MCF-7 cell. These cell deaths did not involve standard apoptosis pathway with caspase-3/7 activation and PARP cleavage. E2, DPN and PPT did not affect the proliferation of ERβ-positive triple negative MDA-MB 231 cell, and IC 50 for 4-OH tamoxifen was too high (8 μM) to be achieved in clinical pharmacological dose. Conclusions: From our cell study, better prognosis of ERβ-positive breast cancer patient who treated with adjuvant tamoxifen is mainly due to its own favorable biological behavior. However, this prognostic impact may include the favorable response to the treatment, when we use estrogen-deprivation therapy such as aromatase inhibitors (AIs). Additional clinical study in AI users would be required to address this issue. No significant financial relationships to disclose.

Patterns of use of tamoxifen and aromatase inhibitors: A population-based observational study

556 Background: Few data are available outside clinical trials on the use of aromatase inhibitors (AI) as adjuvant treatment for early breast cancer (BC). We therefore used a large population-based database to describe patterns of use of AI over time, in comparison with tamoxifen, as well as switches between these regimens. Methods: We identified 13,479 women treated for BC with tamoxifen, anastrazole, letrozole, or exemestane between 1998 and June 2008 in the UK General Practice Research Database (GPRD). Patients were followed from their first prescription for 5 years or until recurrence, death, switch to another treatment or occurrence of a major thromboembolic or uterine event. Results: Mean age at cohort entry was 62 years (SD=14.0) in the tamoxifen group (n=10,806) and 70.8 (SD = 12.4) in the AI group (n=2,673). Overall, in the first year of treatment 88.8% of patients had prescriptions covering more than 80% of the year (88.3% and 90.8% in tamoxifen and in AI group respectively). Table 1 describes prescriptions covering less than 80% of the days for each year of treatment in 3 subgroups. Among women started on AI therapy diagnosed with BC after 2006, 9.6% switched treatment. Half of them switched from one AI to another AI, the other half switched from AI to tamoxifen. Switches occurred within the first year of treatment in 76% of cases. Among women over 50 years of age who started a tamoxifen therapy after 2000, 31% of women switched to AI in the course of the study, of which 12% within the first year of treatment (11.1% and 13.7% for women diagnosed in 2000–2004 and after 2005 respectively). Conclusions: The real-life patterns of use of tamoxifen and AI therapy demonstrate high rates of adherence. However, the relatively high percentage of switchers among AI users is suggestive of an association with side-effects. [Table: see text] No significant financial relationships to disclose.

Prospective Study to Assess Short-Term Intra-Articular and Tenosynovial Changes in the Aromatase Inhibitor–Associated Arthralgia Syndrome

Arthralgia is an adverse class effect of aromatase inhibitors (AIs). To date, its exact mechanism remains unclear. The purpose of this study was to investigate the changes in clinical rheumatologic features and magnetic resonance imaging (MRI) of hands and wrists in AI and tamoxifen users. This is a prospective single-center study including 17 consecutive postmenopausal patients with early breast cancer receiving either tamoxifen (n = 5) or an AI (n = 12). At baseline and after 6 months, patients filled in a rheumatologic history questionnaire and a rheumatologic examination including a grip strength test was done. At the same time points, MRI of both hands and wrists was performed. The primary end point was tenosynovial changes from baseline on MRI. Secondary end points were changes from baseline for morning stiffness, grip strength, and intra-articular fluid on MRI. Wilcoxon signed ranks was used to test changes from baseline and the Spearman correlation coefficient to assess the association between rheumatologic and MRI changes from baseline. At 6 months, patients on AI had a decrease in grip strength (P = .0049) and an increase in tenosynovial changes (P = .0010). The decrease in grip strength correlated well with the tenosynovial changes on MRI (P = .0074). Only minor changes were seen in patients on tamoxifen. AI users reported worsening of morning stiffness and showed an increase in intra-articular fluid on MRI. The functional impairment of hands in the AI-associated arthralgia syndrome is characterized by tenosynovial changes on MRI correlating with a significant decrease in hand grip strength.

A survey among breast cancer survivors: treatment of the climacteric after breast cancer

Aim To evaluate the prevalence and type of menopausal treatments used by breast cancer survivors. To assess factors that impaired the quality of life of these patients.Material and methods A questionnaire assessing quality of life was sent to 325 breast cancer patients. A 66% valid response rate was obtained. Among these responses, 169 women were postmenopausal. The following results concern these patients only.Results Forty-five women were using some treatment to alleviate certain menopausal symptoms (26.6%). More than half of the patients used no therapy to alleviate menopausal symptoms, either because they had no symptoms (n = 43; 25.4%), they feared breast cancer recurrence (n = 24; 14.2%), they were advised not to use a treatment (n = 27; 16%), it had been shown to be inefficient (n = 5; 3%), or because of contraindication (n = 3; 1.8%). In this survey, 62.3% of postmenopausal women affected by breast cancer suffered from hot flushes (n = 94), of which half were severe (n = 46). Among women suffering from hot flushes, a third used various products to alleviate their symptoms (n = 30). Younger women suffered more often from vasomotor symptoms than did older women (p < 0.000). Current users of aromatase inhibitors suffered more from sexual disorders than did non-users (p < 0.001). They had more often an unsatisfactory sexual life (p < 0.01), more vaginal dryness (p = 0.01) and a decreased libido (p < 0.02) compared to non-users.Conclusion More than 50% of postmenopausal women suffered from climacteric symptoms such as hot flushes, but few were taking a treatment to alleviate these symptoms.

How we maintain bone health in early-stage breast cancer patients on aromatase inhibitors.

We often confront the issue of advising otherwise healthy breast cancer survivors, who are likely to be long-term users of aromatase inhibitors (AIs), on the maintenance of bone health. Although our approach is largely based on the American Society of Clinical Oncology (ASCO) guidelines, we outline some practical considerations to this common problem.

Side effects of aromatase inhibitors versus tamoxifen: the patients’ perspective

Background Hormonal therapy is a mainstay in the management of estrogen receptor–positive (ER+) breast cancer. Tamoxifen (TAM) has been the drug widely used until the recent emergence of the aromatase inhibitors (AIs). Although AIs appear to be better tolerated than tamoxifen, they do have a different safety profile and these side effects have not been well characterized in community practice. We surveyed patients with ER+ breast cancers who received adjuvant hormonal therapy to determine how these medications impacted their quality of life and whether side effects or cost influenced decisions to continue therapy. Methods A mailed questionnaire and community cancer registry were used. Results Four hundred fifty-two of 902 surveys were returned for a 50% response rate. Eighty-two percent of respondents were placed on (adjuvant hormonal therapy) some form of estrogen-blocking therapy. Fifty-four percent of these were placed on tamoxifen and 46% on an AI. The most troublesome symptoms for tamoxifen and AI users, respectively, included hot flashes (35%/30%), weight gain (14%/15%), insomnia (17%/17%), and joint aches (12%/23%, P = .002). Thirty-nine percent of TAM users and 46% of AI users were taking medications to control their symptoms. Fifty percent of TAM users and 39% of AI users took vitamin E to help control hot flashes. Forty-two percent of TAM users versus 32% of AI users took Advil (Wyeth, Richmond, VA) for muscle/joint aches; 47.5% of AI users switched medication to improve symptoms as compared with only 37% of tamoxifen users ( P = .015). The average cost of medications to control side effects for both tamoxifen and AI users was $67.36 per month. Conclusions In our survey, both tamoxifen and AI users reported significant and different side effects. AI users suffered more frequently from musculoskeletal complaints, and more AI users switched therapy. Both AI and tamoxifen users used adjunctive medications for symptom control. In both groups, a large number used vitamin E to help hot flashes despite weak evidence to support its effectiveness in this setting. Cost of therapy and symptom control was not a major barrier to care.