Breast Cancer Receiving Aromatase Inhibitors Research Articles

Effects of a 6-month aerobic exercise intervention on brain morphology in women with breast cancer receiving aromatase inhibitor therapy: a sub-study of the EPICC trial.

Physical exercise may increase brain volume and cortical thickness in late adulthood. However, few studies have examined the possibility for exercise to influence brain morphology in women treated for breast cancer. We conducted a nested sub-study within a randomized clinical trial to examine whether 6 months of moderate-intensity aerobic exercise in postmenopausal women with early-stage breast cancer influences brain morphology. We included twenty-eight postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (M age = 62.96 ± 5.40) who were randomized to either 45-60 min of supervised aerobic exercise 3 days/week (n = 16) or usual care (n = 12). Before beginning aromatase inhibitor aromatase inhibitor therapy, and the exercise intervention, and again at 6-month follow-up, volumetric and cortical thickness measures were derived from magnetic resonance imaging scans. There were no significant intervention effects on brain volume and cortical thickness. However, greater average exercise intensity (%) during the intervention was associated with greater post-intervention cortical volume, mean cortical thickness, precentral gyrus thickness, and superior parietal thickness (all p < 0.05). Finally, total supervised exercise time was associated with higher precentral gyrus thickness after the intervention (p = 0.042, R 2 = 0.263). The exercise intervention did not significantly affect brain volumes and cortical thickness compared to the control group. However, positive associations were found between exercise intensity and brain morphology changes after the 6-month intervention, indicating that exercise may reduce the vulnerability of the brain to the deleterious effects of breast cancer and its treatment.

Chemical Shift-Encoded MRI of the Lumbar Vertebral Bone Marrow for Detecting Osteoporosis With Low Trabecular Bone Quality in Patients With Breast Cancer Receiving Aromatase Inhibitors.

Osteoporosis with low trabecular bone quality (OLB) in patients with breast cancer receiving aromatase inhibitor (AI) therapy is associated with an increased risk of vertebral fractures. The capability of chemical shift-encoded MRI (CSE-MRI) in detecting OLB needs to be investigated. To assess the diagnostic performance of proton density fat fraction (PDFF) and R2* measurements from CSE-MRI for detecting OLB in postmenopausal women with breast cancer undergoing AI therapy. Prospective. 126 postmenopausal females (mean age: 69.5 ± 8.8 years) receiving AIs (average period: 41.6 ± 26.5 months) after breast cancer surgery. 1.5-T, three-dimensional CSE-MRI (six echoes), T1-weighted Dixon, short tau inversion recovery, and diffusion-weighted images. Both CSE-MRI and dual-energy x-ray absorptiometry were performed on the same day. Measurements included averaged PDFF, R2*, bone mineral density (BMD), and trabecular bone score (TBS) from L1 to L4 vertebrae. A T-score ≤ -2.5 from BMD measurements indicated osteoporosis, whereas T-scores of ≤ - 2.5 plus TBS ≤-3.7 indicated OLB. The diagnostic performance of PDFF, R2*, and the combination of PDFF and R2* for identifying osteoporosis or OLB was assessed. Student's t-test; Mann-Whitney U test; χ2 or Fisher exact tests; Pearson correlation; multivariate analysis; Receiver operating characteristic (ROC) analysis with the area under the curve (AUC); logistic regression model; intraclass correlation coefficient. A P-value <0.05 was considered statistically significant. For detecting osteoporosis, AUC values were 0.59 (PDFF), 0.66 (R2*), and 0.65 (combined PDFF and R2*). Significant mean differences were noted between patients with and without OLB for PDFF (66.11 ± 5.36 vs. 57.49 ± 6.43) and R2* (46.62 ± 9.24 vs. 63.36 ± 12.44). AUC values for detecting OLB were 0.75 (PDFF), 0.82 (R2*), and 0.84 (combined PDFF and R2*). R2* may perform better than PDFF for identifying OLB in patients with breast cancer receiving AIs. 2 TECHNICAL EFFICACY: Stage 4.

Construction and validation of a risk prediction model for aromatase inhibitor-associated bone loss.

To establish a high-risk prediction model for aromatase inhibitor-associated bone loss (AIBL) in patients with hormone receptor-positive breast cancer. The study included breast cancer patients who received aromatase inhibitor (AI) treatment. Univariate analysis was performed to identify risk factors associated with AIBL. The dataset was randomly divided into a training set (70%) and a test set (30%). The identified risk factors were used to construct a prediction model using the eXtreme gradient boosting (XGBoost) machine learning method. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods were used for comparison. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model in the test dataset. A total of 113 subjects were included in the study. Duration of breast cancer, duration of aromatase inhibitor therapy, hip fracture index, major osteoporotic fracture index, prolactin (PRL), and osteocalcin (OC) were found to be independent risk factors for AIBL (p < 0.05). The XGBoost model had a higher AUC compared to the logistic model and LASSO model (0.761 vs. 0.716, 0.691). The XGBoost model outperformed the logistic and LASSO models in predicting the occurrence of AIBL in patients with hormone receptor-positive breast cancer receiving aromatase inhibitors.

Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause

Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce. To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors. This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022. All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT). The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded. Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean [SD] age, 52.6 [8.3] years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean [SD] score at baseline vs 6 months: CLT, 14.8 [8.8] points vs 20.0 [9.5] points; SLT, 15.6 [7.0] points vs 23.5 [6.5] points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean [SD] difference, 5.2 [1.5] points vs 7.9 [1.2] points; P = .15) or after excluding women who were not sexually active (mean [SD] difference, 2.9 [1.4] points vs 5.5 [1.1] points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean [SD] difference, -4.3 [3.4] vs -4.5 [2.3]; P = .73), Vaginal Health Index (mean [SD] difference, 3.3 [4.1] vs 5.0 [4.5]; P = .17), body image (mean [SD] difference, -3.7 [4.5] vs -2.7 [4.8]; P = .35), and quality of life (mean [SD] difference, -0.3 [3.6] vs -0.7 [3.2]; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean [SD] difference, -0.6 [0.9] vs -0.8 [1.2]; P = .29), vaginal maturation index (mean [SD] difference, 10.2 [17.4] vs 14.4 [17.1]; P = .15), vaginal epithelial thickness (mean [SD] difference, 0.021 [0.014] mm vs 0.013 [0.012] mm; P = .30), vaginal epithelial elasticity (mean [SD] difference, -1373 [3197] Pascals vs -2103 [3771] Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean [SD] Likert scale score, 3.3 [1.3] vs 4.1 [1.0]; P = .007). No differences were observed in complications or serum estradiol levels. In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT. ClinicalTrials.gov identifier: NCT04619485.

Management of bone loss due to endocrine therapy during cancer treatment.

Bone modifying agents BMAs (oral and IV bisphosphonates, denosumab) are used to treat bone loss due to endocrine therapy in patients with hormone receptor positive (HR +) early breast cancer and non-metastatic prostate cancer (NMPC). Timely initiation of appropriate sequential therapy is imperative to reduce cancer treatment-induced bone loss (CTIBL). This narrative review summarizes current literature regarding management of CTIBL in HR + early breast cancer and NMPC patients. Risk factors for fragility fractures, screening strategies, optimal timing for the treatment, dosing/duration of therapy, and post treatment monitoring have not been clearly defined in HR + early breast and NMPC patients receiving endocrine therapy. This review aims to discuss the utility of fracture risk assessment (FRAX) tool for the prevention and management of CTIBL, osteoanabolic therapy for imminent fracture risk reduction, and sequential therapy options. Using predefined terms, PubMed, MEDLINE, and Google Scholar were searched for studies on CTIBL in HR + breast and NMPC patients. We included randomized clinical trials, meta-analysis, evidence-based reviews, observational studies, and clinical practice guidelines. Fracture risk assessment tools (FRAX) guide therapy for osteoporosis in patients with early HR + breast cancer and NMPC. BMAs to prevent bone loss should be initiated at higher T-score than recommended by FRAX in premenopausal HR + breast cancer patients with chemotherapy-induced ovarian failure, oophorectomy and gonadotropin releasing hormone (GnRH) therapy, post-menopausal women with HR + breast cancer receiving aromatase inhibitor therapy, and NMPC patients with androgen deprivation therapy. Sequential therapy with osteoanabolic agents as first line treatment offers a potential therapeutic strategy in patients with high imminent fracture risk. Due to limited data in cancer patients regarding management of osteoporosis, a dosing schedule similar to osteoporosis is considered appropriate. Risk stratification to identify vulnerable patient population, choosing the appropriate sequential therapy, and close monitoring of patients at the risk of bone loss can potentially reduce the mortality, morbidity, and health care cost related to CTIBL.

Long-Term Outcomes of Adjuvant Denosumab in Breast Cancer

BackgroundAdjuvant aromatase inhibitors increase osteoporosis and fractures in patients with hormone receptor–positive breast cancer. We have previously reported outcomes of the ABCSG-18 (study 18 from the Austrian Breast & Colorectal Cancer Study Group) trial showing that adjuvant anti–receptor activator of nuclear factor-κB ligand denosumab treatment counteracts these adverse effects and may improve outcomes. We report here the final long-term outcomes.MethodsABCSG-18 is a prospective, double-blind, placebo-controlled, phase 3 trial in which 3425 postmenopausal patients with early hormone receptor–positive breast cancer receiving aromatase inhibitor therapy were randomly assigned in 58 trial centers to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months. The primary end point was the time to first clinical fracture after randomization. Secondary disease outcome–related end points were disease-free survival (DFS), bone metastasis–free survival (BMFS), and overall survival (OS).ResultsFor this final protocol-defined analysis, median follow-up is 8 years (interquartile range, 6 to 9.6 years). There were 309 versus 368 DFS events (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.97) in the denosumab versus the placebo group, respectively, resulting in an absolute 9-year DFS benefit of 3.5 percentage points (79.4 vs. 75.9%). Adjuvant denosumab improved BMFS by 2.5 percentage points (88.9 vs. 86.4%; hazard ratio, 0.81; 95% CI, 0.65 to 1.00) and OS by 1.0 percentage point (90.9 vs. 89.9%; hazard ratio, 0.80; 95% CI, 0.64 to 1.01). No new toxicities for this dose of adjuvant denosumab were observed.ConclusionsDFS, BMFS, and OS continued to show benefit in this final long-term analysis of ABCSG-18. There were no new toxicities. (Funded by Amgen; ClinicalTrials.gov number, NCT00556374.)

Bone modifying agents for bone loss in patients with aromatase inhibitor as adjuvant treatment for breast cancer; insights from a network meta-analysis.

The data of head-to-head comparisons of the anti-fracture efficacy of bone modifying agents (BMAs) in patients with hormone receptor-positive breast cancer receiving aromatase inhibitor (AI) are not available. Therefore, we conducted a network meta-analysis to compare the efficacy of different BMAs in patients with breast cancer receiving adjuvant AI. We performed a network meta-analysis to compare the change of bone mineral densities (BMDs) and the risk of fracture in the selected studies using a random effect model. The primary outcomes are the change of BMD of lumbar spine (LS) and total hip (TH) from the baseline (ΔBMD, %) at 1 and 2years and the risk of fracture. We identified and included a total of 16 randomized controlled trials for this analysis. All BMAs included (risedronate, zoledronate, and denosumab) were associated with a significant increase in BMD of LS and TH at 1 and 2years compared with no upfront treatment group. Among BMAs, zoledronate and denosumab use resulted in significantly higher BMD of LS and TH at 1 and 2years compared with risedronate. The risk of fracture was significantly lower in the patients who received denosumab or risedronate compared with the patients without upfront treatment (Relative risk (RR) [95% CI] 0.51 [0.38-0.67] and 0.54 [0.35-0.83], respectively). Among the bisphosphonates, zoledronate increased BMD the most, but risedronate, not zoledronate, use was associated with lower risk of fracture. Denosumab increased BMD not only of LS but also of the cortical-bone-rich hip, and showed a significant reduction of fracture risk.

Assessment of Aromatase Inhibitor-Induced Bone Loss and Appropriateness of Supportive Therapy in Postmenopausal Breast Cancer Patients at a Tertiary Care Center

Objective: To assess aromatase inhibitor-induced bone loss (AIBL) and its management in postmenopausal women (PMW) with breast cancer (BC). Materials and Methods: A cohort of 350 PMW with BC receiving aromatase inhibitors (AIs) during a span of 4 years was evaluated retrospectively. Bone mineral density (BMD) of the patients at lumbar spine (LS) and dual femur was monitored at baseline and annually for 2 years. Baseline fracture risk was evaluated using WHO fracture risk assessment tool. Results: At baseline, only 35.4% of the patients received supportive therapy such as calcium and Vitamin D supplements ± bisphosphonates. Significant decrease of mean BMD occurred at LS, left femur, and right femur (LF and RF) at 1 year (P

Dose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen

Dose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen

Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole.

Aim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. Results:SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.

Dietary and Exercise Interventions in Reducing Side Effects in Patients With Stage I-IIIa Breast Cancer Receiving Aromatase Inhibitors

Dietary and Exercise Interventions in Reducing Side Effects in Patients With Stage I-IIIa Breast Cancer Receiving Aromatase Inhibitors

Effect of moderate running training and Mindfulness-based Stress Reduction (MBSR) on immune system and quality of life in women with breast cancer receiving aromatase inhibitors

Effect of moderate running training and Mindfulness-based Stress Reduction (MBSR) on immune system and quality of life in women with breast cancer receiving aromatase inhibitors

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community.Trial registration: Clinicaltrials.govNCT02793921. Registered 20 May 2016.

Bone health assessment by quantitative ultrasound and dual-energy x-ray absorptiometry in postmenopausal women with breast cancer receiving aromatase inhibitors.

Phalangeal quantitative ultrasound (QUS) measurements provide surrogate information on bone quality. The aim of the present study was to assess bone status by phalangeal QUS and by dual-energy x-ray absorptiometry (DXA), and to evaluate bone turnover in breast cancer (BC) women receiving aromatase inhibitors (AIs). Sixty postmenopausal BC women and 42 matched controls were recruited (mean age 61.64 ± 8.33 y). Amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), Ultrasound Bone Profile Index, as QUS parameters, L1-L4 and femoral neck BMD by DXA were assessed at baseline and after 18 months; serum bone-specific alkaline phosphatase (BSAP) and C-telopeptide of type 1 collagen were measured at baseline, 9 and 18 months. FRAX (without BMD) derived 10-years probability of major fractures and hip fractures were significantly associated with AD-SoS (r = -0.381, P = < 0.001 and r = -0.370, P < 0.001, respectively), Ultrasound Bone Profile Index (r = -0.434, P ≤ 0.001 and r = -0.409, P = < 0.001, respectively), BTT (r = -0.309, P = 0.002 and r = -0.340, P = 0.001, respectively). The median percent changes of AD-SoS (-3.71 [-5.38 to 0.11] vs -0.7 [-4.15 to 0.83], P = 0.02 respectively), BTT (-8.4 [-14.91 to -3.53] vs -1 [-5.72 to 3.75], P < 0.001 respectively) were significantly different between AIs users and controls. The same trend was observed for DXA measurements. BSAP and C-telopeptide of type 1 collagen significantly changed in AIs users. AD-SoS was associated with change of BMD at lumbar spine (β, 0.16; SE, 0.08; P = 0.04) and change of BSAP (β, -0.04; SE, 0.02; P = 0.04). Phalangeal QUS appeared a useful tool to evaluate bone quality in BC women on AIs.

Efficacies of aromatase inhibitors in the treatment of hormone dependent metastatic breast cancer in postmenopausal women: a report of 148 cases

To evaluate the clinical efficacies of aromatase inhibitors in the treatment of postmenopausal metastatic breast cancer. A total of 148 postmenopausal women (including bilateral ovariectomy) with hormone dependent metastatic breast cancer receiving aromatase inhibitors (letrozole, anastrozole or exemestane) were analyzed retrospectively. Their clinical efficacies were evaluated. The median progression-free survival (PFS) was 6.5 months and the clinical benefit rate 63.5%. And the rates of PFS of patients on first-line and second-line or above treatments were 9.0 (95% CI: 6.95-11.05) and 3.0 months (95% CI: 1.8-10.1) respectively. The clinical benefit rates of two groups were 74.2% and 26.3% respectively. Aromatase inhibitors are both efficacious and well-tolerated for patients of postmenopausal metastatic breast cancer. It may be recommended as a first-line therapy for postmenopausal women with hormone dependent metastatic breast cancer.

Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial

Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. Amgen.

Identification of Tools to Measure Changes in Musculoskeletal Symptoms and Physical Functioning in Women With Breast Cancer Receiving Aromatase Inhibitors

To estimate and compare responsiveness of standardized self-reported measures of musculoskeletal symptoms (MSSs) and physical functioning (PF) during treatment with aromatase inhibitors (AIs). Prospective, longitudinal study. Park Nicollet Institute and North Memorial Cancer Center, both in Minneapolis, MN. 122 postmenopausal women with hormone receptor-positive breast cancer. MSSs and PF were assessed before starting AIs and at one, three, and six months using six self-reported MSSs measures and two PF tests. MSSs and PF changes from baseline to six months. Using the Breast Cancer Prevention Trial-Musculoskeletal Symptom (BCPT-MS) subscale, 54% of participants reported MSSs by six months. Scores from the BCPT-MS subscale and the physical function subscales of the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) were most responsive to changes over six months. BCPT-MS, AUSCAN, and WOMAC were the most responsive instruments for measuring AI-associated MSSs. Assessment and management of MSSs are important aspects of oncology care because MSSs can affect functional ability and AI adherence. The three measures with the greatest sensitivity were the BCPT-MS, AUSCAN, and WOMAC questionnaires. These measures will be useful when conducting research on change in MSSs associated with AI treatment in women with breast cancer.

Efficacy of a combined alendronate and calcitriol agent (Maxmarvil&lt;sup&gt;®&lt;/sup&gt;) in Korean postmenopausal women with early breast cancer receiving aromatase inhibitor: a double-blind, randomized, placebo-controlled study

The use of aromatase inhibitor (AI) in postmenopausal women with hormone receptor (HR)-positive early breast cancer (EBC) produces a deleterious effect on bone mass and an increase in fractures. Several studies using intravenous bisphosphonates have shown effective management of AI-induced bone loss. To determine whether a lower dosage in oral form combined with calcitriol can effectively manage AI-induced bone loss, we performed a randomized, double-blind, prospective, placebo-controlled 24-week trial with a combination of alendronate and 0.5-µg of calcitriol daily to HR-positive EBC patients. A total of 98 Korean postmenopausal women with HR-positive EBC who received daily AI, calcium and vitamin D were randomly assigned to 5-mg of alendronate and 0.5-µg of calcitriol (Maxmarvil®) or placebo groups. The bone mineral density (BMD) and turnover markers were measured. At week 24, the difference in lumbar BMD between the groups was 3.0% (p < 0.005). The increase in C-telopeptide after 24 weeks was significantly less in the Maxmarvil group compared to that in the placebo group (35.2 ± 17.5% vs. 109.8 ± 28.6%, p < 0.05). Our study demonstrates that a combination of 5-mg alendronate and 0.5-µg calcitriol is effective to prevent bone loss due to AI in Korean postmenopausal women with EBC.

Screening for Osteoporosis in Postmenopausal Women With Breast Cancer Receiving Aromatase Inhibitors: Less Is More?

Advancing age is associated with an increased risk of both breast cancer and osteoporosis. Aromatase inhibitors (AIs) are commonly used to reduce the risk of recurrence in postmenopausal women with early-stage, hormone receptor–positive breast cancer. Estrogen has favorable effects on bone, including stimulation of new bone formation, whereas it inhibits bone resorption through cytokine-mediated osteoclastogenesis. 1 AIs, by inducing an estrogen-depleted state, have been shown to have adverse effects on bone mineral density (BMD) and are associated with fracture rates that vary from 1% to 4%. 2-6 This is seen with both nonsteroidal (letrozole or anastrazole) and steroidal (exemestane) AIs. The use of tamoxifen in the comparator group complicates these studies, given that it functions as an estrogen agonist in bone tissue, thereby preserving bone density and increasing the difference in observed BMD compared with AIs. 7 After completion of treatment, fracture rates return to normal. 8 Markers of bone turnover are also significantly increased with AI treatment. 2-6 The recently reported bone mineral density substudy of the NCIC Clinical Trials Group, MAP.3, a trial of prophylactic exemestane in postmenopausal women at increased risk for breast cancer, provides clarification of the effects of AIs on BMD in the absence of a tamoxifen comparison group. 9 An absolute difference of 1.34% in

Using the 21-gene recurrence score and the recently developed Recurrence Score-Clinical-Pathologic to assess recurrence risk in patients with node-negative, ER-positive early-stage breast cancer receiving aromatase inhibitor treatment alone.

592 Background: The 21-gene Oncotype DX recurrence score (RS) is widely used for assessment of distant recurrence risk and prediction of chemotherapy benefit in patients with early stage ER-positive breast cancer. The Recurrence Score-Clinical-Pathologic (RSPC) risk assessment tool assesses distant recurrence risk when tamoxifen (TAM) therapy is used without chemotherapy, integrating RS with tumor grade, tumor size, and patient age (Tang et al., J Clin Oncol 28:15_suppl, 2010 [suppl; abstr 509]). Neither RS nor RSPC risk assessment have significant treatment interaction with TAM versus aromatase inhibitor (AI) use. Individualized risk assessment when AI therapy is planned would be desirable. Methods: A recent meta-analysis (Dowsett et al, JCO 2010) compares the relative efficacy of AIs and TAM in reducing the risk of distant recurrence. The AI:TAM hazard ratio from the meta-analysis was combined with 10-year risk of distant recurrence as assessed by RS or RSPC for individual N0, ER+ patients to assess the patient’s distant recurrence risk with planned AI therapy. Results: From log rank statistics reported in the AI meta-analysis, we derived a treatment hazard ratio estimate of 0.82 (AI:TAM). Assessments of recurrence risk with AI depend, as expected, on the distant recurrence risk with TAM alone as assessed by RS or RSPC. Confidence interval widths for the AI-alone and TAM-alone risk assessments did not differ greatly. The estimated absolute benefit of AI relative to TAM for 10-year distant recurrence risk in individual patients ranges from about 1% to about 5%. Conclusions: The AI:TAM meta-analysis hazard ratio estimate can be combined with individual patient’s RS and RSPC distant recurrence risk assessment to assess the patient’s distant recurrence risk with planned treatment with AI alone.