Aromatase Inhibitors Users Research Articles

Abstract LB419: Neuroinflammation and aromatase inhibitor associated musculoskeletal syndrome (AIMSS) in breast cancer: Initial insights from [11C]PBR28 PET/MR imaging

Abstract Introduction: While 5-10 years of aromatase inhibitor (AI) treatment clearly improves survival rates of postmenopausal women with hormone-sensitive breast cancer, up to 85% of AI users report aromatase inhibitor associated musculoskeletal syndrome (AIMSS, including arthralgias, myalgias, and muscle stiffness). The biological mechanisms underlying AIMSS are not well understood, but accumulating preclinical and clinical evidence implicate an important role for neuroinflammation in the development and maintenance of other types of chronic musculoskeletal pain (e.g., low back pain, fibromyalgia etc.). The purpose of this pilot study was to investigate the role of neuroinflammation in breast cancer patients with AIMSS. Methods: This cross-sectional case control study used Siemens 3 T integrated positron emission tomography-magnetic resonance imaging (PET/MRI) with the radioligand [11C]PBR28, which binds to the neuroinflammation marker 18kDa translocator protein (TSPO), to assess neuroinflammation in two cohorts (chronic AIMSS, no-AIMSS) of breast cancer patients undergoing AI therapy, and age-, sex- and TSPO genotype-matched healthy controls. Static [11C]PBR28 PET images were reconstructed from 60-90 minutes post-injection. Standardized uptake value (SUV) maps were obtained voxel-wise by normalizing radioactivity by injected dose/body weight. SUV maps were normalized to whole brain to obtain SUV ratio (SUVR) maps. SUVR images spatially normalized to MNI template and then spatially smoothed (FWHM=8mm). Results: Two breast cancer patients (1 AIMSS, 1 no-AIMSS) and 2 matched healthy controls were included in this analysis. Compared to their individual matched healthy controls, both breast cancer patients showed increased [11C]PBR28 signal uptake in the thalamus/midbrain and pons. This elevated signal was more prominent in the breast cancer patient with AIMSS. Conclusions: These preliminary findings suggest an elevated signal of neuroinflammation in the thalamus and brainstem in AI-treatment and AIMSS, aligning with existing literature emphasizing their pivotal role in chronic pain pathology. While it is imperative to acknowledge the limitation of a small sample size, these promising findings suggest a potential role of neuroinflammation for the first time in AIMSS. Future focused Region of Interest (ROI) analysis in thalamus and brainstem with a larger sample size may confirm. Citation Format: Yehui Zhu, Natalie Swanson, Jennifer Murphy, Minhae Kim, Ann Partridge, Robert Edwards, Kristin Schreiber, Marco Loggia. Neuroinflammation and aromatase inhibitor associated musculoskeletal syndrome (AIMSS) in breast cancer: Initial insights from [11C]PBR28 PET/MR imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB419.

Development of cardiometabolic risk factors following endocrine therapy in women with breast cancer.

Studies comparing the effect of aromatase inhibitor (AI) and tamoxifen use on cardiovascular disease (CVD) risk factors in hormone receptor-positive breast cancer (BC) survivors report conflicting results. We examined associations of endocrine therapy use with incident diabetes, dyslipidemia, and hypertension. The Pathways Heart Study examines cancer treatment exposures with CVD-related outcomes in Kaiser Permanente Northern California members with BC. Electronic health records provided sociodemographic and health characteristics, BC treatment, and CVD risk factor data. Hazard ratios (HR) and 95% confidence intervals (CI) of incident diabetes, dyslipidemia, and hypertension in hormone receptor-positive BC survivors using AIs or tamoxifen compared with survivors not using endocrine therapy were estimated using Cox proportional hazards regression models adjusted for known confounders. In 8985 BC survivors, mean baseline age and follow-up time was 63.3 and 7.8years, respectively; 83.6% were postmenopausal. By treatment, 77.0% used AIs, 19.6% used tamoxifen, and 16.0% used neither. Postmenopausal women who used tamoxifen had an increased rate (HR 1.43, 95% CI 1.06-1.92) of developing hypertension relative to those who did not use endocrine therapy. Tamoxifen use was not associated with incident diabetes, dyslipidemia, or hypertension in premenopausal BC survivors. Postmenopausal AI users had higher hazard rates of developing diabetes (HR 1.37, 95% CI 1.05-1.80), dyslipidemia (HR 1.58, 95% CI 1.29-1.92), and hypertension (HR 1.50, 95% CI 1.24-1.82) compared with non-endocrine therapy users. Hormone receptor-positive BC survivors treated with AIs may have higher rates of developing diabetes, dyslipidemia, and hypertension over an average 7.8years post-diagnosis.

(014) Impact of Vaginal Prasterone on the Rate of Urinary Tract Infections in GSM Patients and those on Aromatase Inhibitors: A Retrospective Cohort Analysis

Abstract Introduction The Genitourinary Syndrome of Menopause (GSM) is attributed to a decline in the levels of circulating sexual steroids which often results in increased vaginal pH, atrophic urogenital changes, elevated amount of post-void residual urine, and changes in the vaginal microbiome with a shift towards a predominance of fecal gram-negative bacteria rather than lactobacilli, which is believed to create a potential reservoir for recurrent urinary tract infections (UTIs). Current guidelines to prevent recurrent UTIs include vaginal estrogens. Intravaginal prasterone is converted locally in the vaginal tissue into androgens which are subsequently aromatised into estrogens. It is indicated to treat moderate to severe dyspareunia in postmenopausal women in the US. Objective The objective of this study was to assess, through real world evidence data, the potential of vaginal prasterone to be used in postmenopausal GSM women with recurrent UTIs as prophylaxis to reduce the future UTI risk. As a sensitivity analysis, women using aromatase inhibitors, medications that stop the production of estrogen in postmenopausal women typically prescribed to women with a history of breast cancer, were analyzed. Methods This retrospective matched-cohort study was conducted using the Integrated Dataverse (IDV®) - an open-source claims database from Symphony Health Solutions with data from February 2015 through January 2020. 22,245 women treated with prasterone for a minimum of 12 weeks were matched to women without any prescribed VVA-related treatment. Within each of these two groups, 286 matched patients were taking aromatase inhibitors. Results Across all age groups, women treated with prasterone have a significantly lower UTI prevalence compared to those untreated (6.58% and 12.3%, respectively; p˂0.0001). The highest difference in UTI prevalence among the prasterone treated and untreated women was observed in those aged 65-74 (7.15% and 16.2% respectively; p˂0.0001). Consistent with the above, among aromatase inhibitor users, women treated with prasterone have a significantly lower UTI prevalence (4.90% vs. 9.79%; p=0.008). Conclusions This study suggests that intravaginal prasterone may be a good candidate for prophylaxis in postmenopausal women with recurrent UTIs to reduce future UTI risk, including for patients taking aromatase inhibitors and having contraindications for estrogen-based therapies. This study is however based on real-world evidence and warrants further investigation in a prospective clinical setting. Disclosure Yes, this is sponsored by industry/sponsor: Endoceutics Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endoceutics

MP15-17 IMPACT OF VAGINAL PRASTERONE ON THE RATE OF URINARY TRACT INFECTIONS IN GSM PATIENTS AND THOSE WITH A HISTORY OF BREAST CANCER: A RETROSPECTIVE COHORT ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP15-17 IMPACT OF VAGINAL PRASTERONE ON THE RATE OF URINARY TRACT INFECTIONS IN GSM PATIENTS AND THOSE WITH A HISTORY OF BREAST CANCER: A RETROSPECTIVE COHORT ANALYSIS Rachel Rubin, Erick Moyneur, Katherine Dea, Fernand Labrie, and Alain Dury Rachel RubinRachel Rubin More articles by this author , Erick MoyneurErick Moyneur More articles by this author , Katherine DeaKatherine Dea More articles by this author , Fernand LabrieFernand Labrie More articles by this author , and Alain DuryAlain Dury More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003235.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Genitourinary Syndrome of Menopause (GSM) is attributed to a decline in the levels of circulating sexual steroids which often results in increased vaginal pH, atrophic urogenital changes, elevated amount of post-void residual urine, and changes in the vaginal microbiome with a shift towards a predominance of fecal gram-negative bacteria rather than lactobacilli, which is believed to create a potential reservoir for recurrent urinary tract infections (UTIs). Current guidelines to prevent recurrent UTIs include vaginal estrogens. Intravaginal prasterone is converted locally in the vaginal tissue into androgens which are subsequently aromatised into estrogens. It is indicated to treat moderate to severe dyspareunia in postmenopausal women in the US. The objective of this study was to assess, through real world evidence data, the potential of vaginal prasterone to be used in postmenopausal GSM women with recurrent UTIs as prophylaxis to reduce the future UTI risk. As a sensitivity analysis, women using aromatase inhibitors, medications that stop the production of estrogen in postmenopausal women typically prescribed to women with a history of breast cancer, were analyzed. METHODS: This retrospective matched-cohort study was conducted using the Integrated Dataverse (IDV®) - an open-source claims database from Symphony Health Solutions with data from February 2015 through January 2020. RESULTS: 22,245 women treated with prasterone for a minimum of 12 weeks were matched to women without any prescribed VVA-related treatment. Within each of these two groups, 286 matched patients were taking aromatase inhibitors. Across all age groups, women treated with prasterone have a significantly lower UTI prevalence compared to those untreated (6.58% and 12.3%, respectively; p˂0.0001). The highest difference in UTI prevalence among the prasterone treated and untreated women was observed in those aged 65-74 (7.15% and 16.2% respectively; p˂0.0001). Consistent with the above, among aromatase inhibitor users, women treated with prasterone have a significantly lower UTI prevalence (4.90% vs. 9.79%; p=0.008). CONCLUSIONS: This study suggests that intravaginal prasterone may be a good candidate for prophylaxis in postmenopausal women with recurrent UTIs to reduce future UTI risk, including for patients taking aromatase inhibitors and having contraindications for estrogen-based therapies. This study is however based on real-world evidence and warrants further investigation in a clinical setting. Source of Funding: Endoceutics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e199 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rachel Rubin More articles by this author Erick Moyneur More articles by this author Katherine Dea More articles by this author Fernand Labrie More articles by this author Alain Dury More articles by this author Expand All Advertisement PDF downloadLoading ...

Effects of Endocrine Therapy on Cardiovascular Diseases and Type 2 Diabetes Among Breast Cancer Survivors: The National Health Insurance Service Database of Korea.

Background Although endocrine therapy is an effective treatment for breast cancer, its antiestrogen effects are associated with increased risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the association between endocrine therapy and the risk of cardiovascular diseases and type 2 diabetes among breast cancer survivors in Korea, in consideration of various age groups. Methods and Results In the National Health Insurance Service database of Korea, a total of 133 171 patients with breast cancer aged ≥20 years were included in the current study. Endocrine therapy was treated as time-varying exposure, and patients were categorized as nonusers, selective estrogen receptor modulator users, aromatase inhibitor users, and both users. Time-dependent Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Age at diagnosis, socioeconomic status, histological type, other treatments, and comorbidities were adjusted in the model. Compared with nonusers, selective estrogen receptor modulator users were associated with higher risks of stroke (HR, 1.20 [95% CI, 1.04-1.40]) and venous thromboembolism (HR, 1.47 [95% CI, 1.13-1.90]), whereas aromatase inhibitor users were associated with a higher risk of coronary heart disease (HR, 1.22 [95% CI, 1.06-1.41]). The risk of type 2 diabetes was associated with selective estrogen receptor modulator users (HR, 1.13 [95% CI, 1.05-1.21]), aromatase inhibitor users (HR, 1.14 [95% CI, 1.05-1.23]), and both users (HR, 1.24 [95% CI, 1.10-1.39]). In particular, the risk of a composite of cardiovascular diseases was higher in younger or premenopausal patients. Conclusions In breast cancer survivors in Korea, endocrine therapy is associated with a higher risk of cardiovascular diseases and type 2 diabetes. Monitoring of cancer comorbidities after endocrine therapy is needed in younger and older patients.

Carpal tunnel syndrome and tenosynovitis in women with breast cancer associated with hormone therapy: A multi-institutional analysis using a clinical data warehouse.

The study aims to evaluate the characteristics, treatments, and incidence rates of carpal tunnel syndrome (CTS) and tenosynovitis in women with breast cancer, according to the hormone therapy used. We retrospectively reviewed women with breast cancer identified from the clinical data warehouse of the six hospitals in Korea, from January 2015 to August 2020. Among them, patients with CTS or tenosynovitis were reviewed in terms of disease status and treatments. A total of 101 patients among a population of 15,504 met the study inclusion criteria, so their clinical data were analyzed. Aromatase inhibitor (AI) users frequently needed oral medication for CTS, and developed severe CTS which frequently required surgery. AI users presented with a higher incidence of CTS (1.3%) than patients without hormone therapy (0.4%), and tenosynovitis occurred at a higher rate in AI users (2.3%) compared to the tamoxifen (1.1%) and no hormone groups (0.5%). More than half of the CTS and tenosynovitis occurred within 12 months after hormone commencement. The incidence and disease characteristics of CTS and tenosynovitis differed among the groups depending on the type of hormone therapy received. Our findings will help clinicians understand clinical courses and treatments for CTS and tenosynovitis in breast cancer patients.

Differential impact of tamoxifen and aromatase inhibitors on thrombin generation: the prospective HEMOBREAST cohort

AbstractTamoxifen and aromatase inhibitors (AIs) are potent antitumoral agents against breast cancer. Tamoxifen increases the risk of venous thromboembolism (VTE), but the influence of AIs on the risk of VTE remains unclear. To inform clinical decisions, we evaluated associations of tamoxifen or AIs with changes of surrogate hemostatic biomarkers. This prospective cohort included 107 women with localized breast cancer starting tamoxifen (n = 42) or an AI (n = 65). Thrombin generation (CAT) its sensitivity to thrombomodulin (TM) or activated protein C (APC), and specific coagulation parameters, were measured before and 10-16 weeks after initiation of treatmen Compared with baseline, endogenous thrombin potential and thrombin peak increased in tamoxifen users (+86 nM × min; 95% confidence interval [CI], 30-142; and +33 nM; 95% CI, 21-45) but not in AI users (n = 65; +44 nM × min; 95% CI, −4 to 93; and +7 nM; 95% CI, −3 to 17). Normalized TM sensitivity ratios increased with tamoxifen (+0.26; 95% CI, 0.19-0.33y) but not with AI (+0.02; 95% CI, −0.03 to 0.07). Plasma levels of fibrinogen, antithrombin, protein C, and Tissue Factor Pathway Inhibitor decreased, and free protein S increased with tamoxifen but not with AIs. The observed shift toward increased coagulability associated with tamoxifen is in line with its known increased risk of VTE. In contrast, AIs do not appear to impact hemostasis, suggesting a lack of associated VTE risk. The trial was registered at www.clinicaltrials.gov as #NCT03381963.

Risks of Aromatase Inhibitor-Related Cardiotoxicity in Patients with Breast Cancer in Asia.

Simple SummaryIn Asian breast cancer patients, whether the risks of major adverse cardio- and cerebrovascular events (MACCEs) are different between users of aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs) remains uncertain. In this nationwide cohort study, the risks of MACCEs were significantly higher in users of SERMs compared with users of AIs in those who were at an old age (above 50 years old) or with advanced cancer stage (stage 3–4). Although the choice of hormone therapies is primarily based on the effectiveness regarding cancer survival, AI treatment should be considered for patients for whom the benefits outweigh the risks.Background: Despite a preferred endocrine therapy for women with estrogen and progesterone receptor-positive breast cancer, aromatase inhibitors (AIs) have been reported to increase risks of cardiovascular events. Given that breast cancer patients in Asia are younger at diagnosis, it is urgent to investigate this safety concern. Methods: Through the Taiwanese National Cohort, we identified breast cancer patients initiating selective estrogen receptor modulators (SERMs) or AIs from 2010 to 2016. Outcomes includes major adverse cardio- and cerebrovascular events (MACCEs). The average follow-up duration was five years. Results: We identified 16,730 breast cancer patients treated with SERMs and 11,728 receiving AIs. The population was older and had more comorbidities in the AI group than in the SERM group. After adjusting for age, cancer stage, cancer therapies, cardiovascular drugs and comorbidities, despite similar risks of MACCEs between AI and SERM users, the risk of HF was significantly higher in patients treated with SERMs after adjusted mortality as a competing risk. When divided by the age of 50 years, despite a similar MACCEs in the younger population, MACCEs remained significantly higher in the older population who received SERMs. Conclusions: In this Asian cohort, we found that among patients of old age or with advanced cancer stage, the use of SERMs was associated with a higher risk of cardiovascular events than the use of AIs.

Association Between Aromatase Inhibitors and Myocardial Infarction Morbidity in Women With Breast Cancer: A Meta-Analysis of Observational Studies.

The cardiovascular toxicity of aromatase inhibitors (AIs) for women with estrogen receptor-positive breast cancer is controversial. We aimed to evaluate the association between AIs and the risk of myocardial infarction (MI) in women with estrogen receptor-positive breast cancer based on real-world studies. PubMed, Embase, and Cochrane Library were searched to identify studies that estimated the association between MI risk and AIs. A random-effects model was used to evaluate the hazard ratio (HR) and 95% confidence intervals (CIs) of the predefined outcomes. A total of 134476 patients from eight cohort studies were enrolled in our analysis. For MI incidence, no significant difference was found between the users of AIs and non-users (HR: .98, 95% CI: .83-1.17). The subgroup analysis of patients without a history of cardiovascular disease (CVD) suggested a reduced risk of MI (HR: .86, 95% CI: .77-.96). No significant difference was found for ischemic stroke (HR: .93, 95% CI: .82-1.07) and heart failure (HR: 1.24, 95% CI: .92-1.66) between the two groups. Based on real-world data, AIs may be a safe treatment route for patients with estrogen receptor-positive breast cancer and those with a history of CVD. AIs caused a major decrease in MI in patients without CVD history. However, more in-depth investigations are needed to explore the association between AI use and the incidence of MI in the treatment of estrogen receptor-positive breast cancer.

Indices in dental image exams for bone mineral density evaluation of aromatase inhibitor users

We evaluated the accuracy of radiomorphometric indices (RI) and fractal dimension (FD) for screening bone mineral density (BMD) in postmenopausal patients who had breast cancer and were using aromatase inhibitors (AI). The sample consisted of 40 participants. Digital panoramic radiography (DPR) and cone beam computed tomography (CBCT) were evaluated along with dual-energy X-ray absorptiometry (DXA), which is the gold standard for detecting low BMD. According to the T-scores of DXA, the subjects were assigned into two groups: with normal BMD and with low BMD (osteopenia and osteoporosis). The area under the curve (AUC), sensitivity, and specificity with their respective confidence intervals were determined for DPR and CBCT. For DPR indices, AUC ranged from 52.6 to 75.8%. The mandibular cortical width (MCW) had the highest AUC. For FD, the total trabecular index had the highest sensitivity, while the index anterior to the mental foramen (MF) had the highest specificity. In CBCT, the AUC ranged from 51.8 to 62.0%. The indices with the highest AUC were the molar (M) and anterior (A). The symphysis (S) index had the highest sensitivity and the posterior (P) index had the highest specificity. Sensitivity and specificity were adequate for the computed tomography index (Inferior; CTI [I]). Therefore, MCW, FD of the mandible angle, and total trabecular ROI in DPR and the CTI (I), M, P, and A indices in CBCT proved to be promising tools in distinguishing individuals with low BMD. Cutoff point for these indices could be a useful tool to investigate low BMD in postmenopausal women taking AI.

Endocrine therapy use and cardiovascular risk in postmenopausal breast cancer survivors

ObjectiveExamine the effect of tamoxifen and aromatase inhibitors (AIs) on the risk of 12 clinically relevant cardiovascular outcomes in postmenopausal female breast cancer survivors.MethodsWe carried out two prospective cohort studies...

Evaluation of periodontal health in breast cancer patients undergoing tamoxifen or aromatase inhibitors drugs therapy: A cross-sectional study.

To study the dental and periodontal status of women with breast cancer (BCa) having tamoxifen or aromatase inhibitors (AIs) treatment in comparison with control healthy women. Fifty-one women on tamoxifen therapy, 52 women on AIs therapy and 52 systemically healthy controls were included in the study. The total number of teeth, the number of teeth indicated for extraction, the number of decayed teeth, and the duration of medication were recorded. Periodontal status was evaluated with gingival index (GI); plaque index (PI); bleeding on probing (BOP); probing depth (PD) and clinical attachment loss (CAL). The lowest number of teeth and decayed teeth was found in AIs users (P<.001 and P=.003 respectively). The highest CAL value was seen in AIs users (P=.042) whereas no significant difference was found between the groups in terms of PI, GI, and PD (P=.102, P=.233, and P=.306, respectively). Lower PI was observed in patients using AIs for less than 2 years (P=.048). While tamoxifen did not affect the dental and periodontal condition, AIs medication adversely affected the dental and periodontal condition by more tooth loss and higher CAL.

Abstract PO-077: Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study

Abstract Background: Adjuvant endocrine therapy, including aromatase inhibitors (AI) or tamoxifen, is recommended for women diagnosed with estrogen receptor- and/or progesterone receptor-positive breast cancer as it significantly reduces the risk of recurrence and breast cancer-specific mortality. AIs are the preferred treatment for postmenopausal women; however, concerns have been raised with respect to their cardiovascular safety. Some meta-analyses of randomized controlled trials report an increase in cardiovascular disease (CVD) risk with use of AIs compared to tamoxifen; however, “real-world” observational studies have yielded inconsistent findings. Objectives: We aimed to conduct a population-based study in Scotland to investigate whether breast cancer patients treated with AIs are at an increased risk of cardiovascular disease compared to patients treated with tamoxifen. Methods: Women newly diagnosed with breast cancer, from 2009 to 2017, were identified from the Scottish Cancer Registry. AI and tamoxifen use were identified from the nationwide Scottish Prescribing Information System. The primary outcome was CVD, based on incidence or death from CVD obtained from hospital admission and death records, respectively. Cox regression models calculated hazard ratios (HRs) and 95% intervals (CIs) comparing AI use to tamoxifen use and risk of CVD, using an as treated exposure definition. Analyses were adjusted for a range of potential confounders and subgroup analysis investigated risk by CVD subtypes including myocardial infarction, heart failure, ischemic stroke, venous thromboembolism, and angina. Results: The cohort contained 28,712 breast cancer patients, followed for 110,999 person years, during which there were 776 cardiovascular events. Compared to tamoxifen use, AI use was associated with an increased risk of any CVD event (adjusted HR 1.14, 95% CI: 1.02, 1.27), which was particularly marked for ischemic stroke (adjusted HR 1.27, 95% CI: 0.99, 1.63). There were no clear associations for other CVD subtypes. Conclusions: Our preliminary results suggest an increased risk of CVD, and specifically ischemic stroke, in AI users compared to tamoxifen. Additional analyses will be conducted to further investigate these associations, including dose-response. Citation Format: Lauren McVicker, Christopher Cardwell, Úna McMenamin. Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-077.

Aromatase Inhibitors and Risk of Arthritis and Carpal Tunnel Syndrome among Taiwanese Women with Breast Cancer: A Nationwide Claims Data Analysis.

Tamoxifen or aromatase inhibitor (AI) therapy may prevent breast cancer recurrence, however, adverse effects may lead to treatment discontinuation. Evidence regarding the occurrence of AI-associated musculoskeletal problems among Asians is scarce. We identified women with breast cancer-initiating tamoxifen or AIs from the Taiwan National Health Insurance Research Database (2007–2012). Using multivariable cause-specific hazard models, we examined the association between endocrine therapy and the risk of any arthritis and carpal tunnel syndrome, adjusting for age, prior cancer treatment, and other health status factors. Among 32,055 eligible women with breast cancer (mean age = 52.6 ± 11.5 years), 87.4% initiated tamoxifen, 3.9% initiated anastrozole, 8.0% initiated letrozole, and 0.7% initiated exemestane. AI users had a higher 1-year cumulative incidence for any arthritis (13.0% vs. 8.2%, p < 0.0001) and carpal tunnel syndrome (1.4% vs. 0.8%, p = 0.008). Compared to tamoxifen users, AI users had a higher risk of any arthritis [adjusted hazard ratio (aHR) = 1.21, 95%CI = 1.09–1.34] and carpal tunnel syndrome (aHR = 1.68, 95%CI = 1.22–2.32). No significant difference was observed in the risks of any arthritis and carpal tunnel syndrome across different AIs. Taxane use was not associated with any arthritis (aHR = 0.92, 95%CI = 0.81–1.05) or carpal tunnel syndrome (aHR = 0.97, 95%CI = 0.67–1.40) compared to other chemotherapies. Taiwanese women with breast cancer-initiating AIs had an increased risk of arthritis and carpal tunnel syndrome compared to those who initiated tamoxifen.

Abstract P3-11-25: Real-world treatment patterns and clinical outcomes among women with HR+/HER2- advanced or metastatic breast cancer treated in real-world settings in Italy and Germany

Abstract Background: Palbociclib is a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) that, when combined with an aromatase inhibitor (AI) or fulvestrant, has been shown in clinical trials to prolong progression-free survival (PFS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer (ABC/MBC). This study sought to describe real-world treatment patterns and clinical outcomes among patients with HR+/HER2- ABC/MBC treated with palbociclib in clinical practice settings in Italy and Germany. Methods: MARIA is an ongoing non-interventional, prospective multi-center study that includes women in Italy and Germany initiating their first or second therapy in the HR+/HER2- ABC/mBC setting. Data from 67 sites were used to assess patient and treatment characteristics and progression-free survival (PFS) among patients receiving palbociclib in combination with AI or fulvestrant. Landmark PFS estimates at 6-, 12-, and 18-months were reported by line of therapy (first- and second-line). Results: Overall, 72 patients formed the interim analytic cohort. Among these, 63 (47%) and 9 (7%) received palbociclib + AI as first- and second-line therapy, respectively. Twenty-six (20%) and 37 (27%) of patients received palbociclib + fulvestrant as first- and second-line therapy, respectively. Approximately 96%, 78%, and 64% of patients receiving palbociclib + AI as first-line therapy were progression free at 6-, 12-, and 18-months, respectively. Among patients receiving palbociclib + fulvestrant as first-line therapy, 6-, 12-, and 18-month PFS was 91%, 64%, and 39%, respectively. For second-line therapy, 6-, 12-, and 18-month PFS was 75%, 38%, 38% among palbociclib + AI users and 71%, 54%, and 45% for palbociclib + fulvestrant. Conclusions: This interim analysis indicates that PFS among women with ABC/mBC HR+/HER2-negative breast cancer in Italy and Germany receiving palbociclib, in combination with letrozole or fulvestrant is comparable to published randomized clinical trial results and other real-world observational studies. Further follow-up is required for longitudinal analysis and to estimate overall survival. Funding: Pfizer Citation Format: Michelino De Laurentiis, Nadia Harbeck, Ernest Law, Mayank Ajmera, Debanjali Mitra, Keith Davis, Sara Brucker, Sabino De Placido. Real-world treatment patterns and clinical outcomes among women with HR+/HER2- advanced or metastatic breast cancer treated in real-world settings in Italy and Germany [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-25.

Osteoporotic Fractures of the Spine, Hip, and Other Locations after Adjuvant Endocrine Therapy with Aromatase Inhibitors in Breast Cancer Patients: a Meta-analysis.

BackgroundAromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs.MethodsWe performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls.ResultsThe systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29–1.42; P < 0.001), for hip fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36–2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), respectively, compared to the controls.ConclusionOur meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study.

Background:Tamoxifen (TAM) and aromatase inhibitor (AI) therapies have been associated with increased risk of thromboembolic and cardiovascular events, respectively, in addition to other side effects. This study analysed the risk of these events and the overall survival (OS) benefit in breast cancer patients treated with AI, compared with TAM-treated patients, in a large population-based cohort.Methods:This observational cohort study included women diagnosed with breast cancer and treated with TAM or AI. Data were extracted from primary care records in a population database (SIDIAP, System for the Development of Research in Primary Care). Incidence rates of study outcomes are reported. Survival analyses included Kaplan–Meier estimation and Cox proportional hazards models. Sensitivity analysis was carried out, using Fine and Gray models to account for competing risk of death. Confounding was minimized using propensity score adjustment and inverse probability weighting (IPW) adjustment.Results:Data from 3082 postmenopausal women treated with TAM, and 18,455 treated with AI, were available. Adjusted hazard ratios (HRs) [95% confidence interval (CI)] for AI users, compared with TAM group, were 0.93 (95%CI 0.69–1.26) for thromboembolic events (TEEs); 1.13 (95%CI 0.79–1.63) for cardiovascular events, and 0.76 (95%CI 0.70–0.82) for mortality. Additional analyses using competing risk analysis had similar results, while IPW adjustment showed a potential risk of pulmonary embolism (PE) [2.26 (95%CI 1.02–4.97)] in AI-treated patients.Conclusions:AI users had >20% lower all-cause mortality compared with TAM users, without increasing risk to experience cardiovascular and TEEs. This would locate AI therapy on the first line in clinical practice. Thus, AI might be the most preferable option in adjuvant hormonal therapy choice.

Increased Fracture Risk in Women Treated With Aromatase Inhibitors Versus Tamoxifen: Beneficial Effect of Bisphosphonates.

Aromatase inhibitors have been associated with accelerated bone loss and an increased risk of osteoporotic fractures. Currently, bisphosphonates are recommended to reduce fracture risk in these patients. The aim of this study is to evaluate the fracture risk in breast cancer patients receiving aromatase inhibitors, compared to tamoxifen users, and to assess the effectiveness of oral bisphosphonates in reducing fracture risk. We performed an observational cohort study up to 10 years of follow-up. Data were extracted from primary care records in a population database. Women diagnosed with breast cancer between 2006 and 2015 and treated with tamoxifen or aromatase inhibitors (n = 36,472) were stratified according to low (without osteoporosis diagnosis nor bisphosphonates exposure) or high (with osteoporosis and/or treated with bisphosphonates) fracture risk. Cox models were used to calculate hazard ratios (HR [95% CI]) of fracture from the propensity score-matched patients. Sensitivity analyses account for competing risk of death were performed (subdistribution hazard ratio [SHR] [95% CI]). In postmenopausal women, fracture risk in aromatase inhibitor users showed an HR 1.40 [95% CI,1.05 to 1.87] and SHR 1.48 [95% CI, 1.11 to 1.98], compared to tamoxifen. Observing aromatase inhibitors patients at high risk of fracture, bisphosphonate-treated patients had an HR 0.73 [95% CI, 0.51 to 1.04] and SHR 0.69 [95% CI, 0.48 to 0.98] compared to nontreated. In conclusion, fracture risk in postmenopausal women during aromatase inhibitor treatment, in real-life conditions, was >40% compared to tamoxifen, corroborating previous randomized controlled trials results. In high-risk patients, bisphosphonate users had lower significant fracture incidence during aromatase inhibitor therapy than nonbisphosphonate users. Monitoring fracture risk and related risk factors in aromatase inhibitor patients is advisable. © 2019 American Society for Bone and Mineral Research.

Younger tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and the risk could be reduced by sequenced aromatase inhibitor use: A population-based study in Taiwan.

Objective:Previous Western studies reported that older (≥50 years) breast cancer survivors with tamoxifen treatment had higher risk of endometrial cancer. This study aims to disclose whether younger (<50 years) tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and to examine whether sequenced aromatase inhibitor (AI) use could reduce the risk.Materials and Methods:A population-based cohort of 39,216 newly diagnosed breast cancer patients was identified from Taiwan National Health Insurance Database from 1999 to 2012. The risk of endometrial cancer in nonusers (n = 14,588), tamoxifen-only (n = 19,302), and sequenced AI (n = 5326) users was compared with Cox regression analysis and was adjusted with age, diabetes, hypertension, and chemotherapy.Results:During the 14-year study period, 133 patients were diagnosed with subsequent endometrial cancers. Compared with nonusers, tamoxifen-only users had higher risk of endometrial cancer (14-year incidence 1.7% vs. 0.3%; adjusted hazard ratio [HR] 3.90; 95% confidence interval [CI], 2.37–6.42). This was observed in both older (≥50 years) and younger (40–50 years) age groups. Adjusted HR (95% CI) for the latter was 3.74 (1.65–8.48). This risk persisted after cessation of tamoxifen use. The risk of endometrial cancer was lower in sequenced AI when compared with tamoxifen-only users (adjusted HR 0.43; 95% CI, 0.25–0.72).Conclusions:Not only patients ≥50 years but also younger (40–49 years) patients with tamoxifen treatment had higher risk of subsequent endometrial cancer in this nation-wide cohort. We suggest regular gynecologic monitoring not only during active use but also during follow-up phase. Sequenced AI use may reduce the risk of endometrial cancer in tamoxifen-treated breast cancer patients.

Risk of dementia among postmenopausal breast cancer survivors treated with aromatase inhibitors versus tamoxifen: a cohort study using primary care data from the UK

PurposeAmong a cohort of postmenopausal breast cancer survivors, we aimed to compare the risk of dementia associated with aromatase inhibitor (AI) therapy versus tamoxifen.MethodsUsing UK primary care electronic health records, we identified 14,214 postmenopausal breast cancer survivors (aged ≥ 54 years) with a first AI or tamoxifen prescription between January 2002 and December 2015 and no previous dementia diagnosis. Women were followed-up to identify incident cases of dementia. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between AI exposure (vs. tamoxifen) and dementia, adjusted for confounders.ResultsA total of 368 incident dementia cases was identified over 57,102 person-years of follow-up. The crude incidence rate of dementia was 7.46 per 1000 person-years (95% CI 6.43–8.65) among women starting endocrine treatment on an AI, and 6.32 per 1000 person-years (95% CI 5.34–7.47) among women starting on tamoxifen. After accounting for age differences and assessing other potential confounders, there was no evidence of a difference in dementia risk between exposure groups (HR for AI vs tamoxifen 1.04, 95% CI 0.83–1.03). There was no evidence of effect modification by age.ConclusionThere was no evidence for a difference in dementia risk between AI and tamoxifen users among postmenopausal breast cancer survivors.Implications for Cancer SurvivorsOur findings suggest that there is no reason for concern about a difference in dementia risk with AI vs. tamoxifen, which is relevant to postmenopausal breast cancer patients recommended these treatments.