Aromatase Inhibitors Initiation Research Articles

Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7±1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p<.01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (β=0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (β=-0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (β=-0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (β=-0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

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.

Abstract 804: Temporal trends and disparities by race and ethnicity in treatment of women diagnosed with advanced hormone receptor-positive breast cancer: A SEER-Medicare analysis

Abstract Background: The clinical guidelines for management of advanced hormone receptor-positive (HR+) breast cancer (BC) have changed in the past decade with the addition of novel drug classes. We assessed temporal patterns of treatment initiation among women diagnosed with advanced HR+ BC and examined disparities in treatment initiation by race and ethnicity. Methods: Women aged ≥65 years diagnosed with stage IV or metastatic HR+ BC between 2010-2019 were identified in SEER-Medicare. Poisson models were used to estimate age-adjusted annual incidence rates (IR) and 95% confidence intervals (CIs) for treatment initiation within 12 months of BC diagnosis independently by human epidermal growth factor receptor 2 (HER2) status. Age-adjusted incidence rate ratios (IRR) and 95% CIs were estimated to compare rates of initiation among non-Hispanic Black (NHB) and Hispanic patients with non-Hispanic White (NHW) patients. Results: Among 3,476 eligible patients with a mean age of 76.7 (SD: 7.5) years at diagnosis, 79.6% were NHW, 9.5% were NHB, and 6.0% were Hispanic. Among 2,668 women with HR+/HER2- BC, most initiated on aromatase inhibitors (AIs) alone (56.7%), followed by AIs with palbociclib (12.6%). There was a temporal increase in rates of initiation of AIs with palbociclib (IR [95% CI] per 1000 person-years: 252.8 [240.8, 265.4] in 2015 and 343.9 [330.8, 357.7] in 2019. We did not observe significant differences in rates of initiation of AIs alone or with palbociclib by race and ethnicity. Among 537 HR+/HER2+ patients, 25.0% initiated on AIs alone, 24.6% on pertuzumab and trastuzumab with chemotherapy, 14.3% on trastuzumab with chemotherapy, and 9.1% on AIs and trastuzumab with chemotherapy. IRs (95% CI) for initiation of pertuzumab and trastuzumab with chemotherapy increased from 175.6 (146.3, 210.9) in 2013 to 756.5 (698.3, 819.5) in 2019, while rates for trastuzumab with chemotherapy declined from 963.1 (809.4, 1146.0) in 2010 to 88.4 (72.6, 107.5) in 2019. Rates of initiation of AIs and trastuzumab with chemotherapy remained constant over time. Compared to NHW, NHB and Hispanic women were less likely to initiate pertuzumab and trastuzumab with chemotherapy (IRR [95% CI]: 0.52 [0.27, 1.00] and 0.54 [0.24, 1.23] respectively) and more likely to initiate AIs alone (IRR [95% CI]: 2.23 [1.39, 3.55] and 2.98 [1.69, 5.24] respectively). Conclusions: We observed a temporal increase in the initiation of AIs with palbociclib among patients with advanced HR+/HER2- BC. Among patients with HR+/HER2+ BC, rates of initiating pertuzumab and trastuzumab with chemotherapy increased while rates of trastuzumab with chemotherapy declined. The observed differential management of NHB and Hispanic compared with NHW patients with HR+/HER2+ BC using pertuzumab and trastuzumab with chemotherapy and AIs alone requires further investigation. Citation Format: Kexin Zhu, Elisa Bandera, Farzin Khosrow-Khavar. Temporal trends and disparities by race and ethnicity in treatment of women diagnosed with advanced hormone receptor-positive breast cancer: A SEER-Medicare analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 804.

A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors

Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.

Molecular and clinical effects of aromatase inhibitor therapy on skeletal muscle function in early-stage breast cancer

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I–III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p < 0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p < 0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

Follow-up Routines Matter for Adherence to Endocrine Therapy in the Adjuvant Setting of Breast Cancer.

Endocrine therapy (ET) adherence leads to increased survival in breast cancer (BC). How follow-up should be done to maximize adherence is not known. To assess adherence to ET, factors favouring adherence to ET and effects on survival in a population-based cohort of BC patients in western Sweden. This is a retrospective study. We included 358 patients operated for oestrogen receptor-positive BC and recommended 5 years of ET, in Region Halland, Sweden, year 2015 to 2016. Demographical, clinical and pathological data and use of ET were retrieved from the electronic medical records. Patients were considered adherent if taking ET for 5 years or during the full extent of the follow-up, until termination of ET due to BC relapse or death and where renewals of prescriptions of ET covered ⩾80% of the ordinated dose. Two follow-up routines were employed, ie, routine A where patients were contacted annually by nurses and a more passive follow-up routine B where patients were only contacted by nurses at 2 years and 5 years following start of ET. Medication persistence for 4 years and more was good and similar between patients initiating aromatase inhibitor (AI) and tamoxifen (75.7% and 72.0%, respectively, P = .43). More patients initiating AIs changed ET due to side effects compared with patients initiating tamoxifen (24.3% vs 9.9%, respectively, P < .0001). Endocrine therapy adherence was better for follow-up routine B than for follow-up routine A (hazard ratio [HR] = 2.71 [1.44-5.09], P = .0027). Adherence to ET in BC is high in Western Sweden. Less regular nurse-initiated contacts between BC patients and nursesled surprisingly to a better adherence than a more regular nurse-initiated contact.

Part II: Interactive case: Drug‐induced endocrine disorders

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

Bone health program: A community cancer center's experience.

360 Background: Aromatase inhibitors (AI) are an essential treatment for postmenopausal women with hormone receptor-positive breast cancer in the adjuvant setting. Estrogen deficiency caused by AIs has adverse effects on bone health. Studies reveal that 5 years of treatment with anastrozole led to 6.1% of bone loss at the lumbar spine and 7.2% at the hip. The aim of the project is to identify the current degree of attention to bone health and skeletal-related complications in women with early-stage breast cancer stages I-III that are on AIs at a community cancer center at Einstein Medical Center Montgomery. Methods: This is a retrospective chart review of 63 patients ages 50-85 diagnosed with early-stage I-III breast cancer on an AI in the adjuvant setting. Patients who started on an AI between January 2013 through December 2017 were included. Data on Dual-energy X-ray absorptiometry scans (DEXA) and treatment at baseline, 2-years, and 4-years were analyzed. We followed to see if they had a DEXA scan every 2 years after the baseline DEXA scan for the following 4 years and analyzed information on their bone health. Results: Patients included were on an AI throughout the 4 years. The median age was 60.2 years. 46/63 (73%) had a baseline DEXA scan. Out of these, 12/63 had a normal bone density. 28/63 had osteopenia, of which 16/28 were treated. 6/63 had osteoporosis and only 2/6 were treated. After 2 years, 39/63 (61%) had a 2-year DEXA scan. Of these, 8 had a normal bone density. 26/63 had osteopenia of which 21/26 were treated. 5/63 had osteoporosis and all 5 were treated for this. At 4 years, 40/63 (63%) had baseline DEXA scans. 9/63 had a normal bone density. 21/63 had osteopenia, out of which 17/21 were treated. 10/63 had osteoporosis of which 5/10 were treated. Conclusions: Patients who are being treated with aromatase inhibitors should be evaluated for baseline bone health prior to initiating AIs and every 2 years thereafter. Treatment with bisphosphonates or RANK ligand inhibitors is recommended at an earlier T-score compared to post-menopausal osteoporosis in the absence of breast cancer. In our study, we noticed that the number of patients who did not receive a DEXA scan at the correct time points increased during the period of treatment with the AI. About 53% of patients had osteopenia or osteoporosis at the time of initiation of AIs. The amount of osteoporosis in patients increased from 9.5% at baseline to 15.8% at the 4-year point. This data indicates the need for proper guidelines on DEXA scans and interventions for this patient population. Current interventions planned are patient education Flyers, a patient risk factor checklist in the EMR (Electronic Medical Record) and prompts to review the status of the DEXA report when ordering AIs.

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.

Polypharmacy and premature aromatase inhibitor (AI) discontinuation in older women with breast cancer.

6568 Background: Treatment with AI therapy for at least five years is recommended to reduce risk of cancer recurrence in postmenopausal women with hormone-positive breast cancer, but up to 50% prematurely discontinue their AI. Prior studies have demonstrated higher rates of nonadherence in older patients. Higher rates of comorbidities are also present in older patients, many of which require treatment with prescription medications. However, in prior studies, the impact of polypharmacy on AI persistence in older women has been variable. We evaluated the relationship between use of prescription and over-the-counter (OTC) medications and AI discontinuation in older women in a randomized controlled trial of AI therapy. Methods: In the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, postmenopausal women with stage 0-III hormone-positive breast cancer were randomized to receive exemestane or letrozole and followed for two years. Prescription medication and OTC supplement usage was prospectively collected. Only enrolled participants at least 65 years of age were included in this analysis. Univariate and multivariable Cox proportional hazards models evaluated the association between baseline prescription medications, OTC medications, initial assigned AI medication, and time to discontinuation of initial AI. Results: 131 women at least 65 years old with baseline medication and OTC supplement information were identified. The average age was 70.4 (SD 5). 58 participants (44%) were randomized to exemestane and 73 (56%) to letrozole. 21% had previously received tamoxifen and 18% received taxane-based chemotherapy. The average number of prescription medications at AI initiation was 4.95, and 127 patients reported taking at least one. The average number of OTC medications was 3.23, and 107 patients reported taking at least one. There was no difference in number of prescription medications or OTC medications by study arm. As previously reported, exemestane was associated with premature discontinuation (HR 1.92 [95%CI 1.06-3.50], p = 0.032). Controlling for AI, the risk of discontinuation decreased by 12% for every additional prescription medication (HR 0.88 [95%CI 0.78-0.99], p = 0.038). OTC medication use was not significantly associated with AI duration. Conclusions: Increased prescription medication usage at AI initiation was associated with decreased risk of premature discontinuation of AI. Further research is needed to evaluate this interaction and identify characteristics that impact AI persistence in older women with breast cancer. Clinical trial information: NCT00228956.

Trabecular bone score captures low bone quality in women with normal bone mineral density or osteopenia initiating aromatase inhibitors for breast cancer

Trabecular bone score captures low bone quality in women with normal bone mineral density or osteopenia initiating aromatase inhibitors for breast cancer

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.

Endocrine therapy initiation among women with stage I-III invasive, hormone receptor-positive breast cancer from 2001-2016.

This retrospective cohort study examined patterns of endocrine therapy initiation over time and by demographic, tumor, and treatment characteristics. We included 7777 women from three U.S. integrated healthcare systems diagnosed with incident stage I-III hormone receptor-positive breast cancer between 2001 and 2016. We extracted endocrine therapy from pharmacy dispensings, defining initiation as dispensings within 12months of diagnosis. Demographic, tumor, and treatment characteristics were collected from electronic health records. Using generalized linear models with a log link and Poisson distribution, we estimated initiation of any endocrine therapy, tamoxifen, and aromatase inhibitors (AI) over time with relative risks (RR) and 95% confidence intervals (CI) adjusted for age, tumor characteristics, diagnosis year, other treatment, and study site. Among women aged 20+ (mean 62years), 6329 (81.4%) initiated any endocrine therapy, and 1448 (18.6%) did not initiate endocrine therapy. Tamoxifen initiation declined from 67 to 15% between 2001 and 2016. AI initiation increased from 6 to 69% between 2001 and 2016 in women aged ≥ 55years. The proportion of women who did not initiate endocrine therapy decreased from 19 to 12% between 2002 and 2014 then increased to 17% by 2016. After adjustment, women least likely to initiate endocrine therapy were older (RR = 0.81, 95% CI 0.77-0.85 for age 75+ vs. 55-64), Black (RR = 0.93, 95% CI 0.87-1.00 vs. white), and had stage I disease (RR = 0.88, 95% CI 0.85-0.91 vs. stage III). Despite an increase in AI use over time, at least one in six eligible women did not initiate endocrine therapy, highlighting opportunities for improving endocrine therapy uptake in breast cancer survivors.

Abstract P4-10-19: Aromatase inhibitors and bone health in elderly women with early breast cancer: Real-world data

Abstract Introduction: Aromatase inhibitors (AI) are the mainstay therapy for postmenopausal women with hormone receptor-positive early breast cancer (HR+ EBC). However, their use induces alterations in bone homeostasis, increasing the risk of osteoporosis and fractures, thus impairing quality of life. Elderly women commonly have decreased bone density at the time of EBC diagnosis and AI initiation. Also, this population is usually underrepresented in clinical trials, thus causing scarcity in available data to study the AI long-term effects on bone density among seniors. Hence, we aimed to assess in a real-world setting the clinical impact of bone health management (BHM) in elderly women undertaking AI. Methods: We conducted a 3-year retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI. Patients were stratified according to age: 65-74 (A group) and ≥75 (B group) years old. Statistical analysis of collected data was performed using IBM SPSS v25.0. and StataIC v5.0. Results: A total of 282 patients was included. The median age was 74 years (65-98) and 48.6% of patients enrolled (n=137) were ≥75 years. The median time under AI was 50 months (1-108). AI-associated arthralgia was higher in the elderly group (46.7% vs. 34.5%; p=0.036) that also reported a significantly higher rate of treatment suspension due to AI intolerance (5% vs. 1%; p=0.025). Baseline bone densitometry (BBD) was carried out in a sample of 65.6% of patients and revealed osteopenia or osteoporosis in 82.2% of the sampled individuals. Despite that, only 68.8% and 16.6% of them started calcium/vitamin D supplementation and bisphosphonates therapy, respectively. The incidence of fracture was higher in the B group (17.5% vs. 8.3%; p=0.020), mostly in the radium (25%) and secondary to a fall. Increasing age (p=0.01) and history of previous fracture (p=0.07) independently predicted a fracture event in group B. Adjusting for intrinsic subtype and disease staging, patients with a fracture event had lower disease free-survival (DFS) (HR 4.25 95% CI 0.9-22, p=0.08), but these results were noted only in group A. Conclusions: Our study challenges some perceptions regarding the attention given to bone health in everyday practice. The clinicians' adherence to published guidelines on BHM was overall low, with BBD being performed in only two-thirds of patients. On the positive side, a few clinical suggestions spring from our results. The higher AI intolerance among elderly women opens the opportunity for alternative therapies, such as Selective Estrogen Receptor Degraders (SERD). Fall-preventive strategies should also be implemented especially in high-risk groups such as elderly women under AI. These practice recommendations are likely to foster quality of care and reduce private and public health costs. Citation Format: Mafalda Miranda Baleiras, Leonor Vasconcelos de Matos, Leonor Fernandes, Maria Teresa Neves, Fátima Alves, André Ferreira, Helena Miranda, Ana Martins. Aromatase inhibitors and bone health in elderly women with early breast cancer: Real-world data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-19.

Abstract P5-18-11: Impact of supportive therapies on tolerance of aromatase inhibitors in patients with early-stage, hormone-positive breast cancer

Abstract Background: Aromatase inhibitors (AI) are standard of care in the treatment of early-stage hormone positive (HR+) breast cancer (BC). Commonly, these medications cause significant side effects which limit tolerability and often require a change in therapy. Supportive therapies are an essential part of treatment plans to improve adherence and quality of life. Studies in the last decade have demonstrated the critical role of supportive management in mitigating side effects from AI, such as the reduction in AI related joint pain with acupuncture or use of low dose oxybutynin for hot flashes. The aim of this study was to evaluate the real world use of supportive therapies for AI toxicities over the last decade and to determine if they were associated with patient adherence to initial AI treatment. Methods: We performed a retrospective chart review of all female patients at our academic institution with early-stage, HR+ BC who were initiated on adjuvant AI therapy between 2011-2020. From the electronic medical record, we collected information on patient demographics, AI side effects (hot flashes, vaginal dryness, joint pains, osteopenia/osteoporosis), use of supportive therapies, and duration of first AI therapy. Primary endpoint was the rate of discontinuation of AI at 1 year among those who used supportive therapies compared with those who did not. The Wilcoxon rank sum test, Fisher's exact test, Kruskal-Wallis rank sum test, and Pearson's Chi-squared test methods were used to compare rates of discontinuation of front-line AI therapy for each group. Results: We identified 990 patients (pts) with early-stage, HR+ BC who were started on adjuvant AI between 2011-2020. Of these patients, 97% (n= 963) had AI related side effects yet only 51% (n=504) received supportive therapies. The overall discontinuation rate within 1 year was 14.8% (147 of 990 pts). Patients who received at least 1 supportive therapy were more likely to remain on AI and had a lower 1 year discontinuation rate of 10% (51 of 504 pts) compared to 20% (96 of 486 pts) for those who did not receive any supportive therapy (p&amp;lt;0.001). The most commonly used supportive therapies were bone strengthening agents, with 35.6% (n=352) of patients receiving either denosumab or zoledronic acid, followed by acupuncture used in 11.2% (n=111) of patients. The use of acupuncture increased in 2018, compared to years prior (35 pts from 2011-2017, and 76 pts from 2018-2020). Similarly, oxybutynin use increased in 2019, compared to years prior (9 pts from 2011-2018, and 28 pts from 2019-2020). Upon further analysis, younger age was significantly associated with a higher 1 year discontinuation rate (median age 62 years in &amp;lt;1 year AI treatment group, and 64 years in &amp;gt;1 year AI treatment group, p=0.003). Race also appeared to have an impact on AI tolerance. Although only 31% (39 of 126 pts; p &amp;lt; 0.001) of Black patients received supportive therapy, this group had the lowest 1 year discontinuation rate at 8.7% (11 of 126 pts). Conversely, 56% (277 of 491 pts) of White patients received at least one supportive therapy, yet had the highest 1 year discontinuation rate at 17% (83 of 491 pts). Conclusions: Supportive therapies are essential to help patients mitigate side effects of AI. Patients who received at least one supportive therapy had increased rates of AI adherence beyond 1 year compared to those who did not receive any supportive treatment. The most commonly used therapies were bone strengthening agents and acupuncture. Use of acupuncture and low dose oxybutynin have increased in the past 3 years and 2 years, respectively, following publication of their efficacy. It is critical to further evaluate the impact that race and age have in relation to duration of treatment and use of supportive management. Further studies on how to improve patient tolerability and adherence to AI therapy are needed. Citation Format: Melanie W Kier, Zhiqiang Li, Brittney S Zimmerman, Rima Patel, Yunchen Yang, Mark Y Fink, Jason D Wells, Xiang Zhou, Scott Newman, Rong Chen, Eric Schadt, William Oh, Amy Tiersten. Impact of supportive therapies on tolerance of aromatase inhibitors in patients with early-stage, hormone-positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-11.

Evaluating the role of aromatase inhibitors (AIs) in the treatment of endometrial stromal sarcomas (ESS).

5575 Background: Endometrial stromal sarcomas (ESS) account for &lt; 20% of uterine sarcomas. They usually express estrogen and progesterone receptors (ER/PR) and are considered hormone sensitive. Due to the rarity of these tumors, large clinical trials studying optimal treatment have not been possible. This study represents the largest retrospective study of ESS treated with AI. Methods: The clinicopathological variables and outcomes of patients (pts) with pathologically confirmed low grade ESS treated with AI at our institution between 1998-2020 were recorded. Results: 48 pts with ESS treated with AI were identified. They had a median age of 54 years (range 23-84) and BMI of 27 (range 20-50). 79% were white. 6 (12%), 9 (19%), 14 (29%) and 19 pts (40%) had stage 1,2,3,4 ESS, respectively. 37 (77%) were ER+/PR+; 2 (4%) ER+/PR- and 9 pts (19%) had unknown ER/PR status. All pts were postmenopausal at AI initiation. 12 pts (25%) had a synchronous cancer (5 of these had breast cancer {3 of the 5 presented post tamoxifen}). 23 pts (48%) received megestrol acetate and 25 (52%) an AI as first line hormonal manipulation. During their disease course, 35 pts (73%) received letrozole, 21 (44%) anastrozole and 19 (39.6%) exemestane. 22 pts (46%) were treated with more than one AI. 28 pts (58%) reported side-effects; arthralgia (33%) being the most common. 10 pts (21%) discontinued AI due to toxicity; 12 pts (25%) switched AI for toxicity (with improved tolerance in 67% of these pts). Among the 24 pts (50%) with measurable disease there were 2 partial responses (objective response rate of 8.3%). 1-year disease control rate (DCR) was (79%) for all pts and 58% in stage 4 disease. Median PFS for 1st line AI was 161.6 months (95% CI 48.5 to 274.7). Conclusions: This study represents the largest study of AI use in ESS to date. We found the ORR to be more modest than previously reported. The majority of pts had prolonged stable disease with a DCR of 58% even in stage 4 disease. Pts who progress on one AI may benefit from trial of a 2nd AI. A phase 2 study of interruption versus maintenance AI in locally advanced/metastatic ESS is currently underway (NCT03624244).

Associations between preexisting nociplastic pain and early discontinuation of aromatase inhibitor therapy in breast cancer.

12068 Background: Aromatase inhibitors (AI) are recommended for at least five years to reduce risk of breast cancer recurrence in postmenopausal women with hormone receptor-positive disease. Despite the potential benefit, up to 50% of patients discontinue AI early, primarily because of musculoskeletal side effects. Some patients, including those with fibromyalgia and other chronic pain conditions, have preexisting pain that arises from altered nociception without clear evidence of tissue or peripheral nerve damage, called nociplastic or centralized pain. We hypothesized that preexisting nociplastic pain is associated with early discontinuation of AI therapy due to toxicity. Methods: Patients diagnosed with breast cancer between 2012-19 and who enrolled in the Michigan Genomics Initiative (MGI) were identified. Patients who were female, had hormone receptor-positive breast cancer, had not received neoadjuvant therapy, and who initiated adjuvant AI therapy were included in the analysis. Prior to breast cancer surgery patients completed surveys about pain in the affected breast and overall worst pain (Brief Pain Inventory [BPI]), nociplastic pain (2011 Fibromyalgia Survey [FS], which assesses widespread pain plus somatic symptom severity), and anxiety (PROMIS Anxiety 4a v.1). Demographics, cancer characteristics, and treatment history, including date and reason for discontinuation of AI therapy, were abstracted from the medical record. Patients were censored at date of last oncology follow-up. Univariate and multivariable analyses were conducted to assess relationship between age, BMI, surgical site pain, overall worst pain, FS score, anxiety, and time to discontinuation of initial AI medication. Results: Of 207 analyzed patients, the average age was 61 years, average BMI was 30.3 kg/m2, 181 (87%) were postmenopausal at the time of breast cancer diagnosis, and 31% received chemotherapy. The majority were prescribed anastrozole (n=196); 6 took letrozole and 5 took exemestane. Average scores prior to surgery were 1.5/10 for worst pain, 0.2/10 for surgical site pain, 4.2/31 for FS score, and 54.1/100 for anxiety. On univariate analysis, only use of exemestane (HR 5.55, p&lt;.001) and use of letrozole (HR 3.11, p&lt;.001) were associated with shorter time to ET discontinuation; age, BMI, surgical site pain, worst pain, FS score, and anxiety were not statistically significantly associated with time to AI discontinuation. On multivariable analysis, only higher FS score was statistically significantly associated with time to AI discontinuation (HR 1.11, p=.021). Conclusions: Greater pre-existing nociplastic pain was associated with early discontinuation of AI therapy. For these patients, early interventions that target centralized pain, or treatment with tamoxifen instead of AI therapy, may be appropriate in order to reduce risk of nonpersistence with AI therapy.

A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting.

Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37). Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy. Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.

Most women with breast cancer about to initiate aromatase inhibitors already have bone loss

Women with breast cancer who receive aromatase inhibitors (AI) are at risk of bone mass loss and bone fracture. Many of these women have been previously treated with chemotherapy and/or tamoxifen, also with known deleterious bone effects. We studied the bone mineral status of a group of postmenopausal women with non-advanced breast cancer about to initiate AI treatment.Between 2007 and 2010, 127 women aged 63±9 years were prospectively included. Clinical, epidemiological, analytical, radiological, and densitometric data were collected.Prior to initiating AI treatment, the patients exhibited a high prevalence of bone mass loss (62.2%): 16.5% had osteoporosis and 45.7% osteopenia by OMS criteria. Besides, 7.4% of their dorso-lumbar spine x-rays revealed one or more vertebral fractures, all of which were found in patients with densitometry-defined osteoporosis or osteopenia. Surprisingly, 25-OH-vitamin D levels were normal (≥30 ng/ml) in 87.4% of the women. Obesity was prevalent (BMI 30±5). Their most common tumour was infiltrating ductal carcinoma (76.4%). The women who had received adjuvant chemotherapy (50%) were younger (59.1±8.3 vs. 66.2±8.2, p<.0001), and had greater total hip bone mass (.988±.138 vs. .935±.119, p=.048). The patients that had taken tamoxifen (37%) more often exhibited normal bone mass (55.3% vs. 27.5%, p=.009), and had greater bone mass at the femoral neck (.893±.113 vs. .826±.131, p=.003). In addition, they had lower bone turnover: lower osteocalcin (4.4±2.8 vs. 8.2±6.7, p<.0001) and deoxypyridinoline (7.1±2.4 vs. 8.3±3.3, p=.037).This study shows that more than 60% of women about to initiate aromatase inhibitors for non-advanced breast cancer have low bone density and so high risk of fracture or re-fracture. These facts underscore the importance of screening their bone mass status and propose them preventive treatment.

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).