Initiating Aromatase Inhibitor Therapy Research Articles

Abstract PO2-19-12: Enhancing skin appearance and quality of life in breast cancer survivors on aromatase inhibitor therapy

Abstract Background: Post-menopausal women with estrogen receptor positive breast cancer (BC) are typically prescribed endocrine therapy with an aromatase inhibitor (AI) for 5-10 years following BC diagnosis. AIs have multiple established side effects related to estrogen deprivation including vasomotor symptoms, vaginal dryness, and accelerated bone thinning. Many patients also complain about the impact of AIs on skin quality; however, limited data currently exists, particularly with objective measurements of skin quality. Canfield Sciences VISIA-CA is a device that can be used to objectively measure skin changes using patented comparison to norms analysis with a skin feature database to grade the skin relative to others in the same age and skin type. Herein, we aim to evaluate changes in skin quality with the Canfield Sciences VISIA-CA Device after initiation of AI therapy and investigate potential benefits of skincare intervention. Trial Design: This is a pilot study aiming to describe changes in skin quality after initiation of AI therapy in BC survivors through use of VISIA-CA technology and patient reported outcome measures. This study will allow us to collect data and identify the trend (if any) for a future larger study. Patients who consent for participation are given a baseline survey to assess self-reported quality of life, perception of skin quality, and self-image prior to initiation of AI. Patients also receive baseline skin measurement with the VISIA-CA device and facial skin photography. Baseline skincare regimen is documented. Any patients on prescription tretinoin products at time of baseline assessment are excluded from the study. Patients return 6 months after initiation of AI for follow-up surveys, updated VISIA-CA measurement, and facial skin photography. Patients then meet with a Mayo Clinic Cosmetic Center aesthetician for skincare intervention with recommended topical treatments including daily facial cleanser, exfoliator, toner, hydrating crème, and retinol-based product. Patients return for additional visits with updated survey, VISIA-CA measurement, and facial skin photography at 1 month, 3 months, and 6 months after skincare intervention. Patients are asked to complete skincare compliance diary to document adherence on a weekly basis. Eligibility Criteria: Post-menopausal patients with newly diagnosed ER-positive BC at Mayo Clinic Florida are identified for participation in the study prior to beginning AI therapy. Specific Aims: 1.) Evaluate the incidence and severity of skin changes after initiation of AI therapy in BC survivors through use of Canfield Sciences VISIA-CA technology, facial skin photography, and validated patient reported outcome measures. 2.) Assess for objective improvements in skin quality measurements after skincare intervention including a retinol-based product Statistical Methods: Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). The changes of skin measurement and patient reported outcome measurements will be calculated and summarized for the following time frames: 1) from initiation of AI therapy to 26 weeks after 2) from the initiation of skincare intervention and 4 weeks, 12 weeks, and 26 weeks after. Appropriate statistical plots will be used to illustrate the change. Target Accrual: 50 patients. Schedule of Events Citation Format: Lauren Cornell, Leila Tolaymat, Pooja Advani, Saranya Chumsri, Pincelli Thais. Enhancing skin appearance and quality of life in breast cancer survivors on aromatase inhibitor therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-12.

Part II: Interactive case: Drug‐induced endocrine disorders

Part <scp>II</scp>: Interactive case: <scp>Drug‐induced</scp> endocrine disorders

Denosumab effect on bone mineral density and urinary-NTX in breast cancer patients receiving aromatase inhibitors.

Aromatase inhibitors are used post-surgical intervention in postmenopausal patients with breast cancer. However, these drugs accelerate decline in bone mineral density (BMD), which is countered by use of denosumab, and the efficacy of the drug can be assessed by bone turnover markers. We investigated the effects of denosumab administration for 2years on BMD and urinary N-telopeptide of type I collagen (u-NTX) levels in breast cancer patients treated with aromatase inhibitors. This was a single-center retrospective study. Postoperative hormone receptor-positive breast cancer patients with low T-scores biannually received denosumab from the time of initiation of aromatase inhibitor therapy for 2years. BMD was measured every 6months, and u-NTX levels were assessed after 1month and thereby every 3months. The median patient age of the 55 patients included in this study was 69 (range: 51-90) years. BMD gradually increased in the lumbar spine and femoral neck and u-NTX levels were lowest at 3months post-initiation of therapy. Patients were divided into two groups based on the change ratio of u-NTX 3months post-denosumab administration. Of these, the group with higher change ratio showed a higher degree of BMD restoration in the lumbar spine and femoral neck 6months post-denosumab treatment. Denosumab increased BMD in patients treated with aromatase inhibitors. The u-NTX level decreased soon after start of denosumab treatment, and its change ratio is predictive of improvement in BMD.

The impact of bone mineral density screening on incident fractures and healthcare resource utilization among postmenopausal breast cancer survivors treated with aromatase inhibitors

Postmenopausal women with hormone receptor-positive breast cancer (BC) often receive aromatase inhibitor (AI) therapy. However, AIs induce bone loss and BC survivors are at an increased risk of bone fractures. This study determined whether receipt of baseline dual-energy x-ray absorptiometry (DXA) screening is associated with decreased incident fractures and lower healthcare resource utilization. We retrospectively analyzed 22,713 stage 0-III primary BC survivors who received AI therapy ≤ 1year prior to BC diagnosis from the Medicare-Linked Surveillance, Epidemiology, and End-Results database. We categorized DXA screening for those who had a procedural claim within 12months prior through 6months after first AI claim. We used propensity score methods to assess the association of DXA screening with bone fractures and health resource utilization. Of the study cohort, 62% received a DXA screening. Women with comorbid dementia, renal disease, and congestive heart failure were less likely to receive a DXA. After adjusting for confounders, BC survivors who received a DXA had a 32% decreased risk of any bone fracture compared to those who did not (hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.60-0.76, p < 0.001). Similarly, those who received a DXA were less likely to be hospitalized (HR 0.73 (0.62-0.86)) or use outpatient services (HR 0.85 (0.74-0.97)). Bone density screening is associated with decreased incident bone fractures and a lower likelihood of utilizing healthcare resource for fracture-related events. Postmenopausal BC survivors treated with AIs should undergo appropriate bone density screening to reduce morbidity, mortality, and health care expenses.

327 Nociplastic pain and early discontinuation of aromatase inhibitor therapy in breast cancer patients over age 65

OBJECTIVES/GOALS: Side effects are why up to 50% of women with hormone-positive breast cancer prematurely discontinue aromatase inhibitor (AI) therapy. Pain from altered nociception without clear tissue/nerve damage (nociplastic) is a hypothesized contributing factor to this. Our objective was to evaluate the relationship between nociplastic pain and AI duration. METHODS/STUDY POPULATION: Patients with breast cancer diagnosed between 2012-19 were identified from the University of Michigan Genomics Initiative (MGI). Patients who were female, &gt;65 years old at time of breast cancer diagnosis, and had hormone receptor-positive disease met inclusion criteria. Prior to undergoing surgery, patients completed validated surveys about overall worst pain (Brief Pain Inventory [BPI]), nociplastic pain (2011 Fibromyalgia Survey [FS]), and life satisfaction, with higher scores representing more of the factor. Breast cancer history, treatment, and patient demographics were abstracted from the medical record. Univariate analysis was conducted to evaluate the relationship between age, body-mass index (BMI), chemotherapy, BPI, FS, life satisfaction, and time to discontinuation of initial AI. RESULTS/ANTICIPATED RESULTS: 207 patients were eligible, 133 of whom initiated AI therapy. Of the 133 analyzed patients, mean age was 70.7 years and mean BMI was 30.3. 28 (21%) underwent adjuvant chemotherapy and 79 (59%) received adjuvant radiation prior to initiation of AI therapy. Average nociplastic pain score was 4.0/31 (standard deviation [SD] 4.6), worst pain was 1.5/10 (SD 1.9), and life satisfaction score was 7.3/10 (SD 2.8). The initial AI for 94% of patients (125 patients) was anastrozole. On univariate analysis, only higher nociplastic pain score was statistically associated with premature discontinuation of AI with a HR 1.07 (95%CI 1.00-1.13, p = 0.036). On multivariable analysis, no factors remained statistically significant, although there was a trend for nociplastic pain (HR 1.06, 95%CI 1.00-1.13, p = 0.068). DISCUSSION/SIGNIFICANCE: It is important to identify variables predicting tolerance to therapy so patients can be optimally counseled. Our study suggests that patients with pre-existing baseline pain disorders may be more likely to be nonpersistent with AI therapy. Future study should be conducted to determine if treatments for nocipastic pain improve AI persistence.

Bone Mineral Density at the Time of Initiating Aromatase Inhibitor Therapy Is Associated With Decreased Fractures in Women With Breast Cancer.

Women with estrogen receptor-positive breast cancer who receive an aromatase inhibitor (AI) are at risk for fractures. We aim to determine if dual-energy X-ray absorptiometry (DXA) scans made at the time of AI initiation are associated with decreased fractures. We retrospectively identified 25,158 women with local or regional breast cancer diagnosed between 2005 and 2013 who received AI therapy between 2007 and 2013 from the Medicare-linked Surveillance, Epidemiology, and End Results Program and Texas Cancer Registry databases. We defined baseline DXA screening using claims made between 1 year before and 6 months after each patient's first AI claim to examine determinants of baseline screening using a multivariable GENMOD model. We included a propensity score adjustment in Cox proportional hazard models to assess the association between time-varying DXA screening and the risk of fractures. Additionally, we compared the use of antiresorptive therapy drugs between the two groups. Of the study cohort, 14,738 (58.6%) received DXA screening. The screening rates increased annually from 52.1% in 2007 to 61.7% in 2013. Higher screening rates were observed in patients with younger age, married status, non-Hispanic white race, localized disease, fewer comorbidities, more than one type of aromatase inhibitor drug claim, no state buy-in (surrogate for low socioeconomic status), higher education level, and prior osteoporosis diagnosis. Baseline DXA screening was associated with decreased risk of subsequent fractures (hazard ratio=0.91; 95% confidence interval, 0.86-0.97, p < .001) after multivariable and propensity score adjustment. Bone-modifying drugs were prescribed to 4440 (30.1%) patients with screening compared with 1766 (16.9%) without (p < .001). Of the 4440 patients who received treatment, 95% received bisphosphonates. Our study demonstrated baseline DXA screening was associated with a decreased risk of fractures and a higher likelihood of receiving antiresorptive therapies. Improvement of the baseline DXA screening is still needed in practice. © 2021 American Society for Bone and Mineral Research (ASBMR).

The Use and Concurrent Use of Side Effect Controlling Medications Among Women on Aromatase Inhibitors.

Background: Women on aromatase inhibitors (AIs) as part of their breast cancer treatment often experience difficult to control side effects. Although there are several medications to manage the side effects of AI therapy, many of them are associated with their own risk, particularly sedation. The objective of this study was to describe the prescribing practices for side effect managing (SE) medications among women with breast cancer on AI therapy and to assess for combinations of medications that may present a clinical risk to patients. Methods: Retrospective data analysis using Surveillance, Epidemiology and End Results (SEER)-Medicare data of all women aged 66-90 years with stage I-III hormone positive breast cancer diagnosed between 2008 and 2014 who initiated AI therapy within 12 months of their diagnosis. We determined the percentage of patients prescribed an SE medication in the 12 months prior and in the 24 months after the initiation of AI therapy. We calculated the number of prescriptions and the number of days of overlapping (i.e., >1 SE) prescriptions, and examined predictors of overlapping prescriptions. Results: The use of SE medications was pervasive and increased after initiation of AI therapy. The most commonly prescribed medications were opiates (55.1%), selective serotonin reuptake inhibitors (22.6%), benzodiazepines (18.4%), tramadol (17.7%) and gabapentin (14.6%). In total 15.5% of patients had overlapping prescriptions; among those, 36.2% had three overlapping prescriptions. Prior use was the strongest predictor of overlapping prescriptions with an odds ratio of 7.9 (95% confidence interval: 7.17-8.77). Conclusion: Among women on AI therapy, the use of SE medications is common and many have overlapping prescriptions raising concern for potential harm from polypharmacy.

Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients.

Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer. One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia. More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia. Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.

Early-stage breast cancer (BC) patients: Factors associated with aromatase inhibitor-induced musculoskeletal symptoms.

525 Background: Hormone receptor positive (HR+) breast cancer comprises the largest subgroup of breast cancer. Aromatase Inhibitors (AI) are a key treatment for HR+ BC patients (pts) and reduce mortality. Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS), defined as myalgias, arthralgias, or joint stiffness, occur in up to 50% of pts leading to low adherence to and often discontinuation of therapy. Little is known of the mechanism of AIMSS or its predisposing risk factors. This study aims to identify risk factors associated with AIMSS development in BC patients on AI therapy. Methods: We conducted a medical record review of pts with non-metastatic HR+ BC on adjuvant AI therapy between January 2009 and June 2017 at the University of Maryland Comprehensive Cancer Center. This study included 194 ptswho were free of arthralgia prior to AI therapy. We analyzed pts’ demographics, lifestyle factors, reproductive history, tumor characteristics, medications, cancer treatment, co-morbidities, AI type, onset and severity of AIMSS. Severe AIMSS was defined as requiring change in AI therapy or discontinuation. Multivariable-adjusted logistic regression was used to identify risk factors for severe AIMSS. Results: The mean age of participants was 61. The mean BMI at diagnosis was 30 kg/m2. 41% of pts were White, 40% were Black, 7% other and 12% unknown. Most (79%) did not have a history of tamoxifen and 16% were on GnRH agonists. Most (71%) used letrozole as initial AI therapy; 18% anastrozole; and 11% exemestane. 56% experienced AIMSS while on AI therapy and 20% required change or hold of AI therapy. 4% permanently discontinued AI due to AIMSS severity. BMI at diagnosis was significantly positively associated with risk of AIMSS. Multivariate odds ratio (95% confidence intervals) comparing the highest to lowest tertile of body mass index (BMI) at diagnosis was 4.01 (1.07-10.90; Ptrend: 0.05). There were no significant associations with race, smoking, reproductive factors, type of AI therapy, tamoxifen use prior to AI therapy, medication use, experience of other cancer treatments, and tumor characteristics. Conclusions: 56% of BC pts on adjuvant AI therapy experienced AIMSS. 24% of these changed, held or discontinued AI regimen due to severe AIMSS. Higher BMI at diagnosis was associated with a higher risk of AIMSS. Our results confirm clinical significance of AIMSS among BC pts on AI therapy and suggest BMI as a modifiable factor for AIMSS. A larger study is warranted to replicate our findings and seek other possible risk factors for AIMSS.

Abstract P5-12-13: Factors associated with aromatase inhibitor associated musculoskeletal symptoms in early stage breast cancer patients

Abstract Introduction: Aromatase Inhibitors (AI) are a mainstay of treatment for hormone receptor positive breast cancer (BC) in postmenopausal women. However, patients under AI treatment often suffer from Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS), defined as myalgias, arthralgias, or joint stiffness in hands, fingers, knees, hips and feet, which may limit treatment and subsequently increase BC mortality. The depletion of estrogen following AI initiation has been postulated to cause AIMSS. However, it has not yet been fully established about the clinical significance of AIMSS and its risk factors and the underlying mechanisms. The aim of this study is to identify epidemiologic risk factors associated with the development of AIMSS in BC patients on adjuvant AI therapy. Methods: We conducted a retrospective review of medical records among 111 stages 0-III hormone receptor positive BC patients who received adjuvant AI therapy, including anastrozole, letrozole or exemestane, between January 2009 and June 2017, at the University of Maryland Greenebaum Comprehensive Cancer Center. To be eligible, women had to be either postmenopausal or premenopausal, on a GnRH analog for at least 3 months, and report of no AIMSS before the AI initiation. We collected patients’ data on demographics, lifestyle factors, reproductive histories, tumor characteristics, types of AI and cancer treatment, co-morbidities, use of medications, length of AI therapy, and onset and severity of AIMSS. We defined severe AIMSS as AIMSS requiring the change of AI therapy or discontinuation of AI. The demographics and clinicopathological characteristics of patients on AI therapy and frequencies of AIMSS onset during AI treatment was characterized with means (SDs) or percentages. To estimate the association of severe AIMSS with epidemiologic risk factors, odds ratios (ORs) and 95% confidence intervals were calculated using multivariable-adjusted logistic regression. Results: This study included 111 BC patients with a mean age of 64 years. Their mean BMI at time of BC diagnosis was 30.8 kg/m2, and 41% of patients were White, 39% were Black, 4% were Asian/Pacific Islander, and 16% were other. Majority of patients (77%) had no prior experience of tamoxifen use and used letrozole as an initial AI therapy (70.3%); 15.3% used anastrozole, and 14.4% used exemestane. We found that 52.6% of patients experienced any degree of AIMSS while on AI therapy. In particular, 19.8% of patients required change or holding AI therapy, and 3.6% permanently discontinued AI because of AIMSS. We observed that older age at AI therapy initiation and higher levels of circulating vitamin D-25OH were significantly associated with lower odds of severe AIMSS. Multivariate ORs (95% Cis) comparing the highest to the lowest tertile of age and vitamin D levels at AI initiation were 0.18 (0.05-0.71) and 0.10 (0.02-0.49), respectively (all P-trend: ≤ 0.04). There were no significant association between race, body mass index, smoking, alcohol use, reproductive factors, type of AI therapy, and tamoxifen use prior to AI therapy. Conclusions: In our study, nearly 52.6% of BC patients on adjuvant AI therapy experienced AIMSS. Of those, 23.4% changed or discontinued AI regimen due to severe AIMSS. Older age and higher circulating levels of vitamin D-25OH at the initiation of adjuvant AI therapy were associated with lower risk of developing severe AIMSS. The study results support the clinical significance of AIMSS in BC patients leading to decreased adherence to AI therapy. The replication of our association with age and vitamin D levels in a larger study is warranted as it may provide a greater insight into etiologies of AIMSS. Citation Format: Yamin Sun, Simran Elder, Seungyoun Jung, Candace Mainor, Shruti Murali, Paula Rosenblatt, Katherine Tkaczuk. Factors associated with aromatase inhibitor associated musculoskeletal symptoms in early stage breast cancer patients [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 P5-12-13.

Fracture Risk in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study.

Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. Using a population-based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure (n = 1,775), women with breast cancer not receiving AIs (n = 1,016), and women from the general population (n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users). At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures. In a population-based observational registry that included 1,775 patients initiating long-term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure.

Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

IntroductionOsteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment.MethodsThis descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endocrine sensitive breast cancer, aged 50 to 80 years. A baseline questionnaire documented demographic-, medical-, lifestyle- and fracture history. Body weight was assessed clinically, and body composition and BMD measured via dual energy absorptiometry (DXA). Data was analysed in STATA 14 using descriptive and inferential statistics.Results101 participants were recruited, with a mean age of 61±7 years. Nearly a third (n = 32) of women at baseline fulfilled global criteria for bone protection (BMD T-score ≥-2SD (n = 18); BMD T-score -1.5SD to < -2SD with risk factors (n = 14). Lower body weight, body mass index (BMI), fat mass index and lean mass index were significantly associated with the participants with a BMD measurement in keeping with a diagnosis of OP (p <0.001). Low vitamin D was present in 93% of the cohort tested (n = 95), whilst deficient vitamin D status (<20ng/ml) was documented in 52 women (55%).ConclusionsIn this study, a third of postmenopausal women considered for AI therapy fulfilled international criteria for bone protective pharmacological intervention. This emphasizes the need for clinical risk and BMD assessment in postmenopausal breast cancer patients at baseline. Body composition and bone health associations highlight bone fragility associated with lower body weight.

Effect of Aromatase Inhibitor Therapy on Sleep and Activity Patterns in Early-stage Breast Cancer

IntroductionAdherence to aromatase inhibitor (AI) therapy is poor, often because of treatment-emergent side effects, including musculoskeletal symptoms, fatigue, and insomnia. In the present analysis, we examined the sleep patterns and daytime function both objectively using actigraphy and subjectively using validated questionnaires in women initiating AI therapy. Patients and MethodsPostmenopausal women with stage 0-III hormone receptor-positive breast cancer who were initiating AI therapy were eligible. The patients wore actigraphy devices for 10 consecutive days and completed questionnaires at baseline before the initiation of AI and after 3 months of AI therapy. Associations between the baseline demographics and symptoms, changes in patient-reported outcomes and actigraphy measures from baseline to 3 months of AI therapy and discontinuation of AI therapy were examined using sign tests, logistic regression models, Spearman's correlation, and linear mixed models. ResultsForty-two patients (86%) completed the baseline assessments and 23 patients (47%) completed both the baseline and the 3-month assessments. Objectively measured daytime function as measured by total daytime activity decreased during the 3 months after starting AI (232,566 activity count vs. 204,205 activity count; P = .023), and the decrease was more evident in women with higher baseline physical function. Reduced daytime activity correlated with increased fatigue (ρ = −0.49; P = .017). ConclusionDaytime function decreased after initiation of AI therapy and correlated moderately with increased fatigue, although no association was identified with changes in pain or sleep quality. Additional studies are required to understand why function is reduced, which could have implications for interventions to improve patient tolerance of, and persistence with, AI therapy.

Optimal duration of adjuvant endocrine therapy: how to apply the newest data.

Background:The benefit of 5 years of adjuvant endocrine therapy for women with hormone receptor-positive (HR+) breast cancer (BC) is beyond discussion. Nevertheless, the risk of recurrence of luminal BC persists for 15 years or more after diagnosis. Consequently, approaches of extended adjuvant therapy have been investigated in large clinical trials, with the ultimate aim of further reducing the risk of recurrence in patients with HR+ BC.Methods:A review of recently published trial data is presented to provide a solid basis for discussion. A discussion of the side effects of long-term endocrine treatment, multigenetic tests aiming to identify patients at particular risk, and an outlook for further promising targets are additional aims of this review.Conclusion:Extended adjuvant therapy seems beneficial in reducing distant relapse and contralateral BC for a selected group of patients with HR+ BC, particularly if aromatase inhibitors (AIs) are used after initial tamoxifen therapy. However, patients with lower risk of recurrence and initial AI therapy may suffer more from side effects than benefit from extended therapy.

Hair loss associated with aromatase inhibitor treatment among breast cancer patients.

e21619 Background: Hair loss and thinning have been reported by breast cancer patients treated with aromatase inhibitors (AIs); these side effects are documented to be reasons that patients discontinue their AI therapy and have been shown to be associated with a decrease in quality of life. Despite this knowledge, there is a paucity of detailed data on hair changes over the course of AI therapy. The purpose of this study was to examine hair changes and risk factors for hair loss among breast cancer patients initiating aromatase inhibitor therapy and followed for one year. Methods: Data were analyzed from a cohort of 146 breast cancer patients initiating AI therapy and followed over the first year of their AI treatment. At baseline (prior to AI therapy) and at 1-year, a questionnaire was administered that ascertained data on demographics, health behaviors, and symptoms. Detailed hair loss questions, including those pertaining to family history and specific location of hair loss, were added during the study period when study staff noticed that hair loss and thinning were commonly being reported on the symptom checklist after initiation of AI therapy. Multivariable logistic regression analysis was conducted to examine factors related to AI-attributed hair loss. Results: Among the 86 breast cancer patients who completed the detailed hair loss survey at 1-year (mean age = 63y), 43% reported experiencing hair loss after the initiation of AI therapy. The most frequently reported time period of onset of the AI-attributed hair loss was between 3 and 6 months post-AI initiation (43.2%), with 67.6% of patients noting hair loss in the mid-scalp (top of head). Factors significantly associated with AI-related hair loss at 1-year were: hair loss prior to AI therapy, having a BMI &gt; 30 kg/m2(odds ratio (OR) = 6.5), being a current smoker (OR = 7.8), and maternal history of hair loss or hair thinning (OR = 9.1). ORs were similar when patients with prior chemotherapy were excluded. Conclusions: Hair loss is a common side effect of AI therapy that can negatively affect a patient’s quality of life and potentially lead to treatment discontinuation. Treatment options for this AI-related side effect should be explored, especially for patients who are at increased risk.

Durable complete remission with aromatase inhibitor therapy in a patient with metastatic uterine carcinosarcoma with poor performance status and coagulation disorders: a case report

BackgroundChemotherapy is considered the most appropriate treatment for metastatic uterine sarcoma, despite its limited efficacy. No other treatment has been conclusively proved to be a real alternative, but some reports suggest that anti-hormonal therapy could be active in a small subset of patients. We report the case of a patient with metastatic uterine carcinosarcoma with positive hormonal receptors and a complete pathological response.Case presentationA 54-year-old white woman presented to our emergency room with hypovolemic shock and serious vaginal bleeding. After stabilization, she was diagnosed as having a locally advanced uterine carcinosarcoma with lymph nodes and bone metastatic disease. In order to control the bleeding, palliative radiotherapy was administered. Based on the fact that positive hormone receptors were found in the biopsy, non-steroidal aromatase inhibitor therapy with letrozole was started. In the following weeks, her general status improved and restaging imaging tests demonstrated a partial response of the primary tumor. Ten months after initiating aromatase inhibitor therapy, she underwent a radical hysterectomy and the pathological report showed a complete response. After completing 5 years of treatment, aromatase inhibitor therapy was stopped. She currently continues free of disease, without further therapy, and maintains a normal and active life.ConclusionsThis case shows that patients with uterine carcinosarcoma and positive hormone receptors may benefit from aromatase inhibitor therapy. A multidisciplinary strategy that includes local therapies such as radiation and/or surgery should be considered the mainstay of treatment. Systemic therapies such as hormone inhibitors should be taken into consideration and deserve further clinical research in the era of precision medicine.

A prospective study of aromatase inhibitor therapy initiation and self-reported side effects.

The objective of this study was to examine the associations between aromatase inhibitors (AIs) and side effects less frequently reported in the literature, including difficulty concentrating, forgetfulness, hair loss, and numbness in the extremities. Data were analyzed from a cohort of 146 breast cancer patients initiating AI therapy and followed for 1year and a cohort of 144 postmenopausal women without a history of cancer followed for 6months. At baseline (prior to AI therapy for breast cancer patients), and at 3months, 6months, and 1year (for breast cancer patients only), a comprehensive questionnaire was administered that ascertained data on symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression for new onset of symptoms among the breast cancer patients compared to the women without a history of cancer. Among thebreast cancer patients, 34.2% were treated with chemotherapy prior to AI treatment. Over the first 6months of AI treatment, breast cancer patients had significantly higher odds of reporting new onset of forgetfulness (OR 4.00; 95% CI 1.67, 9.59), difficulty concentrating (OR 2.73; 95% CI 1.29; 5.78), hair loss (OR 4.12; 95% CI 1.86, 9.17), and numbness/tingling in the extremities (OR 2.47; 95% CI 1.09, 5.62) compared to women without a history of cancer. Similar increases in odds were observed for the subgroup of women not treated with chemotherapy versus the comparison group. AI-related symptoms should be monitored and addressed so that adherence to therapy is maintained.

Abstract P5-12-03: Prevalence of bone loss among nonmetastatic breast cancer patients treated with aromatase inhibitors in the United States

Abstract Background: Adjuvant endocrine therapy compromises bone health in patients (pts) with breast cancer, leading to osteopenia, osteoporosis, and fractures (Forbes 2008). For postmenopausal women with estrogen receptor (ER) positive (+ve) breast cancer, aromatase inhibitors (AI) have emerged as the standard of care because of superior efficacy over selective ER modulators such as tamoxifen, shown in several large clinical trials. As rates of utilization and duration of AI therapy are expected to continue to increase, we report estimates of the prevalence of women with nonmetastatic breast cancer treated with AI in the United States and examine evidence of bone loss before and after AI exposure. Methods: The Oncology Services Comprehensive Electronic Records (OSCER) database, an electronic medical record database on &amp;gt;500,000 cancer pts from oncology practices across the US, was used to identify women with breast cancer (ICD-9 174*), ≥1 clinic visit, and confirmed AI therapy (anastrozole, letrozole, or exemestane) in 2014, excluding pts with evidence of metastases (ICD-9 196-198, stage IV, or M1 disease). OSCER is projected nationally through methods of direct estimations utilizing claims data for 1-year period prevalence. Bone loss was defined by diagnosis of osteoporosis (ICD-9 733.0), osteopenia (ICD-9 733.90), or receipt of bone therapy in 2014. Bone therapies used as proxy for bone loss were intravenous (IV) (ibandronate, zoledronic acid), or oral bisphosphonates (BPs) (risedronate, ibandronate, etidronate, alendronate), or subcutaneous anti-RANK ligand antibody (denosumab [60 mg Q6M]). Results: It is nationally estimated that 538,630 (95% CI 519,839 - 557,422) women with nonmetastatic breast cancer were treated with an AI in 2014, representing a median of 6 prescriptions (mean 6.8). Of these, most (94%) were treated with anastrozole or letrozole, 55% were ≥65 years, and 11% took tamoxifen prior to first AI. Among women taking AI in 2014, 39% started in 2014, 24% started in 2013, and 37% have been on AI therapy since 2012 or earlier. Overall, 285,543 (53%) pts on AI therapy had evidence of bone loss, 30% of whom developed bone loss after exposure to AI therapy. Among the 338,784 women with no evidence of pre-existing bone loss, 25% (85,697) developed bone loss after initiating AI therapy (table), with 21% treated with oral and 1% IV BPs, or 9% with denosumab. 2014 prevalenceN (%)Nonmetastatic pts on AI therapy538,630At least 2 AI prescriptions in lifetime468,608 (87)Bone loss before starting AI199,846 (37)No bone loss before AI, with bone loss after AI85,697 (16) Conclusions: This study provides current estimates of the prevalence of nonmetastatic breast cancer treated with AI in the US using real-world data, indicating that more than 535,000 women were treated with AI in 2014. Considering that 37% of pts have been on endocrine therapy since 2012 or earlier, continued use of AI will likely lead to increased pts with bone loss. These women face an increased risk of fractures, highlighting the need for intervention with antiresorptive treatments (i.e., BPs have been studied, and denosumab has a labeled indication in this setting) that may help build bone mass and counteract detrimental effects on the bone. Citation Format: Pirolli M, Hernandez RK, Reich A, Liede A. Prevalence of bone loss among nonmetastatic breast cancer patients treated with aromatase inhibitors in the United States. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-03.

Effect of Aromatase Inhibitor Therapy on the Cardiovascular Health of Black and White Breast Cancer Patients

BackgroundThe present study examined racial differences in the cardiovascular health effects of aromatase inhibitors. Patients and MethodsData were analyzed from 77 white and 35 black patients with early-stage breast cancer initiating aromatase inhibitor therapy and subsequently followed for 1 year. At baseline and a 1-year follow-up clinic visit, a comprehensive cardiovascular health assessment was conducted, which included measurement of carotid intima-medial thickness and a blood draw to measure high-sensitivity C-reactive protein and cholesterol concentrations. A detailed questionnaire was also completed. The information collected was used to calculate each patient's 10-year risk of atherosclerotic cardiovascular disease events at both measurement points. Paired t tests were used to examine the changes in the continuous outcome variables within groups during the study period. Independent t tests were conducted to examine the changes over time between the 2 groups. ResultsNo statistically significant changes in carotid intima-medial thickness, atherosclerotic cardiovascular disease risk score, or the other cardiovascular-related outcomes (high-sensitivity C-reactive protein, cholesterol levels, blood pressure) during the first year of aromatase inhibitor therapy were observed among either the black or white breast cancer patients or between the 2 groups. Mean grip strength in the dominant hand decreased significantly and similarly during the 1-year period for the white and black breast cancer patients. ConclusionThe findings from the present study suggest no large adverse cardiovascular health effects from aromatase inhibitors during the first year of therapy among either black or white breast cancer patients. However, the results of the present study cannot rule out the potential for long-term adverse changes over the duration of aromatase inhibitor therapy or beyond.

Crossover from one aromatase inhibitor (AI) to another in the Exemestane and Letrozole Pharmacogenetics (ELPh) trial.

158 Background: Tolerance of AI therapy can be poor due to treatment-emergent toxicities and can lead to early discontinuation (non-persistence). Patients often switch from one AI to another when toxicities develop; however, limited prospective data exist on patients who switch AI. Here we describe the effect of switching from E to L or L to E on tolerance of and persistence with therapy. Methods: Postmenopausal women initiating AI therapy were enrolled on the ELPh trial and randomized to E or L. Those that stopped their AI for self-reported intolerance were offered crossover to alternate AI after a 2-6 week washout. Kaplan-Meier estimates of proportions on AI after 1, 3, and 6 months were assessed during 1st and 2nd AI. Associations between time on 2ndAI and clinicopathologic factors were analyzed using univariable Cox proportional hazards model. To evaluate effect of crossover on patient-reported outcomes, multiple questionnaires, including a pain visual analog scale (VAS), were assessed serially. Results: 83 women, mean age 60 years, 45% prior chemotherapy, and 31% with prior tamoxifen use, participated in the crossover protocol. 71% reported improvement in symptoms a mean 4.72 weeks after discontinuing 1st AI therapy. Median time on 1st AI was 6.8 months (95% CI 5.8-9 months), and on 2nd AI was 11.5 months (6.9-24.2). The probability of persistence at 1, 3, and 6 months for the 1st AI was 94%, 76%, and 55% and for the 2nd AI was 89%, 73%, and 62%, respectively. There was no significant association between duration on 2nd AI and 1st AI (L vs. E), duration on 1st AI, age, body mass index, or prior therapies. The change in pain VAS from baseline to 1 or 3 months was not significantly different during treatment with the 1st or 2ndAI. Conclusions: Although all AI medications have similar mechanisms of activity, nearly two-thirds of patients who are intolerant of one AI are able to maintain therapy for at least 6 months following switch to 2nd AI. Switching is a reasonable approach for women who cannot tolerate 1st AI that may improve persistence with therapy. The mechanisms for intrapatient variation in tolerance warrant further study. Clinical trial information: NCT00228956.