Discontinuation Of Adjuvant Endocrine Therapy Research Articles

Active symptom monitoring for premenopausal women with breast cancer initiating adjuvant endocrine therapy: Protocol for the SWOG S2010 randomized controlled efficacy trial

BackgroundPremenopausal women with early stage, high risk hormone receptor positive breast cancer are at risk of early discontinuation of adjuvant endocrine therapy (ET), primarily because of toxicity, which can increase the risk of disease recurrence and death. We hypothesize that identification of bothersome symptoms between clinic visits, and automated notification of clinicians about symptoms, will result in improved persistence with ET. MethodsPre- and perimenopausal women planning to receive adjuvant treatment with tamoxifen or an aromatase inhibitor plus ovarian function suppression or ablation for treatment of breast cancer are eligible. A total of 540 participants will be enrolled and randomized 1:1 to patient education with or without Active Symptom Monitoring (ASM). The ASM intervention includes 6 symptom questions (hot flashes, sadness, anxiety, insomnia, vaginal dryness, joint pain) that will be completed via text, email, or telephone weekly for 24 weeks, then every 4 weeks for 48 weeks. All participants will complete a battery of questionnaires every 12 weeks to examine symptoms, beliefs about medicine, self-efficacy, and ET adherence. Optional blood draws will be collected at baseline and after 12, 48, and 72 weeks of therapy to examine estradiol and ET concentrations. The primary endpoint is time to nonpersistence with initially prescribed ET within the first 72 weeks, evaluated using Kaplan-Meier plots and multivariable Cox regression. ConclusionWe expect early identification and management of ET-related toxicities to improve persistence with breast cancer therapy, breast cancer outcomes, and quality of life for premenopausal women at high risk of breast cancer recurrence.Clinicaltrials.govNCT05568472

Familial adversity: association with discontinuation of adjuvant hormone therapy and breast cancer prognosis.

Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in breast cancer patients. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and breast cancer-specific mortality. By cross-linking seven Swedish health registers, we performed a cohort study including all breast cancer patients who initiated adjuvant hormone therapy during 2006-2019 in Sweden (N = 10,701). A group-based multi-trajectory model was used to identify familial adversity groups based on three dimensions: material deprivation, negative family dynamics, and loss or threat of loss. Cox proportional hazard models were used to investigate associations of familial adversity with hormone therapy discontinuation and breast cancer-specific mortality. We identified five distinctive familial adversity groups among the cohort participants. Compared to women with low familial adversity, higher risks to discontinue adjuvant hormone therapy were observed among women with material deprivation (hazard ratio (HR), 1.31; 95% CI, 1.20-1.43), negative family dynamics (HR, 1.16; 95% CI, 1.06-1.28), loss or threat to loss (HR, 1.15; 95% CI, 1.00-1.32), or high familial adversity (HR, 1.53; 95% CI, 1.40-1.68). Furthermore, women with material deprivation (HR, 1.37; 95% CI, 1.05-1.79), negative family dynamics (HR, 1.41; 95% CI, 1.01-1.97), or high adversity (HR, 1.67; 95% CI, 1.26-2.23) were at higher risks of dying from breast cancer. Familial adversity is associated with a higher risk of adjuvant hormone therapy discontinuation and breast cancer-specific mortality. Family-related factors identified in our study may help identify high-risk patients for interventions to prevent treatment discontinuation and subsequently improve breast cancer outcomes.

Feasibility of Symptom Monitoring During the First Year of Endocrine Therapy for Early Breast Cancer Using Patient-Reported Outcomes Collected via Smartphone App.

Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

Association of Sarcopenia With Toxicity-Related Discontinuation of Adjuvant Endocrine Therapy in Women With Early-Stage Hormone Receptor–Positive Breast Cancer

Sarcopenia, an age-related decline in muscle mass and physical function, is associated with increased toxicity and worse outcomes in women with breast cancer (BC). Sarcopenia may contribute to toxicity-related early discontinuation of adjuvant endocrine therapy (aET) in women with hormone receptor-positive (HR+) BC but remains poorly characterized. This multicenter, retrospective cohort study included consecutive women with stage 0-II HR+ BC who received breast conserving therapy (lumpectomy and radiation therapy) and aET from 2011 to 2017 with a 5-year follow-up. Skeletal muscle index (SMI, cm2/m2) was analyzed using a deep learning model on routine cross-sectional radiation simulation imaging; sarcopenia was dichotomized according to previously validated reports. The primary endpoint was toxicity-related aET discontinuation; logistic regression analysis evaluated associations between SMI/sarcopenia and aET discontinuation. Cox regression analysis evaluated associations with time to aET toxicity, ipsilateral breast tumor recurrence (IBTR), and disease-free survival (DFS). A total of 305 women (median follow-up, 89 months) were included with a median age of 67 years and early-stage BC (12% stage 0, 65% stage I). A total of 60 (20%) women experienced toxicity-related aET discontinuation. Sarcopenia was associated with toxicity-related early discontinuation of aET (odds ratio, 2.18; P=.036) and shorter time to aET toxicity (hazard ratio [HR], 1.62; P=.031). SMI or sarcopenia were not independently associated with IBTR or DFS; toxicity-related aET discontinuation was associated with worse IBTR (HR, 9.47; P=.002) and worse DFS (HR, 4.53; P=.001). Among women with early-stage HR+ BC who receive adjuvant radiation therapy and hormone therapy, sarcopenia is associated with toxicity-related early discontinuation of aET. Further studies should validate these findings in women who did not receive adjuvant radiation therapy. These high-risk patients may be candidates for aggressive symptom management and/or alternative treatment strategies to improve outcomes.

Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy Among Patients With Breast Cancer

A large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy. To examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy. This population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022. Discontinuation of adjuvant hormone therapy. The main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy. A total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results. In this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.

Management of adjuvant endocrine therapy (AET) side effects in patients with breast cancer: A single cancer center experience.

e12503 Background: Up to 50% of breast cancer survivors are unable to complete the recommended 5-year course of adjuvant endocrine therapy (AET), usually due to side effects. Patients who develop side effects may change to a different medication (‘switch’) or may treat side effects with additional medications or non-pharmacologic strategies. While there are numerous evidence-based treatments available for side effects of AET, the benefit of switching AET is less well known. We have previously reported on the association between switching and early discontinuation of AET. Here, we provide further insight into the use of switching vs side effect management at our cancer center. Methods: We conducted a retrospective chart review of patients diagnosed between 2011-2014 with early stage, ER+/HER2- breast cancer. Clinical data extracted by chart review included side effects and treatment history. Patients were grouped based on whether they received a switch vs side effect management and compared for variables of interest using Chi-squared tests and confidence intervals. Multiple logistic regression was used to assess long-term adherence, adjusting for side effect type and severity. Results: A total of 228 patients with early-stage ER+/HER2- breast cancer were evaluated. Among them, 162 patients (71.0%) received treatment for side effects. A medication switch was offered in 98/162 (60.5%) cases, with side effect management (SEM) alone offered in the remaining (39.5%). Patients who switched were more likely to have reported severe side effects compared to patients who received SEM alone (OR 4.56, 95% CI (2.1, 9.8), p < 0.001). Hot flashes were more frequent in patients who received SEM compared with those switching (89% vs 59%, respectively, p < 0.001), while arthralgias were more frequent in the patients who were offered a switch (70% vs 47%, p = 0.002). ‘Other’ side effects were also more frequent in patients who switched (58% vs 30%, p < 0.001). Among patients who discontinued therapy early, the majority did so within the first 12 months (18/43, 42%). The long-term adherence rate was 73% overall, and it was significantly lower in the subset of patients who received a switch compared to those who received SEM – 62% vs 91% respectively, p < 0.001. Significance was maintained after adjusting for side effect type and severity with multiple logistic regression, p = 0.013. Conclusions: Despite limited evidence, rates of switching are high in clinical practice. Switching is more common in patients with severe symptoms, and those who report arthralgias and uncommon side effects. Switching was associated with poor long-term adherence. Due to the potential for selection bias, conclusions are limited as to whether switching itself is ineffective. A prospective randomized trial is under development at our cancer center to address this question.

Abstract OT1-04-01: AMEERA-6: Phase 3 Study of Adjuvant Amcenestrant Versus Tamoxifen for Patients With Hormone Receptor-Positive Early Breast Cancer, Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity

Abstract Background: About 30% of patients (pts) with hormone receptor (HR)-positive early breast cancer (EBC) on adjuvant aromatase inhibitor (AI) therapy discontinue due to toxicity with 22% of pts discontinuing during the first year (Henry et al. JCO 2012). For these patients who struggle with adjuvant AIs, there are limited alternatives including switch to a different AI which may have similar side effects, tamoxifen, or observation. This paucity of effective and tolerable options may contribute to poor adherence and/or early discontinuation of adjuvant endocrine therapy, which is associated with worse outcomes. Amcenestrant (SAR439859) is an optimized oral selective estrogen receptor degrader (SERD) with potent dual activity which antagonizes and degrades the estrogen receptor (ER), resulting in inhibition of the ER signaling pathway. In the phase 1/2 AMEERA-1 first-in-human trial (SABCS 2020 PD8-08), amcenestrant showed strong antitumor activity and favorable safety profile in the treatment of HR+ metastatic breast cancer. The phase 2 window-of-opportunity study AMEERA-4 evaluating two doses of amcenestrant demonstrated robust Ki67 reductions, strong engagement of the ER target, and continued to show a favorable safety profile in an early breast cancer population. Based on pharmacodynamic activity, safety, and emerging results from other ongoing amcenestrant trials, the 200 mg daily dose of amcenestrant was selected for the AMEERA-6 study. Trial Design: This is a prospective, randomized, international, double-blind, double-dummy, phase 3 superiority study of amcenestrant versus tamoxifen. Eligible pts are men and women with any menopausal status with HR+ stage IIB/III breast cancer, irrespective of human epidermal growth factor receptor 2 (HER2) status. If neoadjuvant systemic therapy was administered, pts must have residual nodal disease after definitive breast surgery (ypN1-3). Pts will be centrally assessed to have ER-positive and/or progesterone receptor-positive (≥10% positive stained cells) status by immunohistochemistry assay. Pts must have received at least 6 months of adjuvant AIs (≥3 months in the adjuvant setting if they received prior neoadjuvant AI) and discontinued within 30 months of initiation due to AI-related toxicity. Pts may have been treated with more than one AI. All adjuvant therapies including chemotherapy, anti-HER2 treatment, cyclin-dependent kinase (CDK) 4/6 inhibitor, and/or poly (ADP-ribose) polymerase (PARP) inhibitors must be completed or stopped prior to randomization. 3738 pts will be randomized 1:1 to receive either amcenestrant 200 mg daily or tamoxifen 20 mg daily for 5 years and will be followed for 10 years from randomization. Men and pre/peri-menopausal women will also receive a GnRH analog. Extended adjuvant endocrine therapy upon completion of study treatment is allowed per investigator discretion. Stratification factors include duration of prior AI therapy, HER2 status and prior chemotherapy, prior CDK4/6 inhibitors, geographic region, and menopausal status. The primary endpoint is invasive breast cancer-free survival (IBCFS) based on STEEP criteria version 2.0 defined as occurrence of first recurrence of the disease: ipsilateral or regional invasive, distant recurrence, contralateral invasive breast cancer and death. Key secondary endpoint is invasive disease-free survival (IDFS) and other secondary endpoints include overall survival, safety, patient reported outcomes, and pharmacokinetics of amcenestrant. Adherence to treatment and biomarkers are exploratory endpoints. AMEERA-6 recruited the first patient in March 2022 and is being conducted in partnership with AFT, BIG, EORTC, and Sanofi. Clinical trial information: NCT05128773 Citation Format: Otto Metzger, Christina Herold, Coralie Poncet, Heidi De Swert, Jose Casas-Martin, Ann Partridge, Samia Guita, Lisa Carey, Eva Schumacher, Theodora Goulioti, Thomas Meyskens, Joseph Gannon, Khadija Benlhassan, Giovanna Rossi, Eleni Xenophontos, Amal Arahmani, Amylou C. Dueck, Gautier Paux, Etienne Brain, David A. Cameron. AMEERA-6: Phase 3 Study of Adjuvant Amcenestrant Versus Tamoxifen for Patients With Hormone Receptor-Positive Early Breast Cancer, Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-04-01.

Abstract P4-03-01: Persistence with adjuvant endocrine therapy in patients with early breast cancer at high risk of recurrence: a US-based real-world study

Abstract Background: Previous studies have highlighted concerns regarding treatment persistence (TP) of patients with early breast cancer (EBC) taking adjuvant endocrine therapy (ET) but these data have not been analyzed based on patient’s risk of recurrence. The aim of this study is to evaluate the TP of patients at high risk of recurrence based on clinicopathologic criteria used in the monarchE trial. Methods: This observational retrospective cohort study used nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of US patients diagnosed with EBC from Jan 2011 to Sept 2020. Overall, 4028 patients were selected based on the following criteria: adult female or male with diagnosis of HR+, HER2– EBC (stage IA-IIIC) with no evidence of distant metastasis who received surgical resection and adjuvant endocrine therapy. Patients were divided into 2 groups; GroupA: patients with clinicopathologic features suggestive of high risk of recurrence: ≥4 positive(+) axillary lymph nodes (ALN), OR 1-3+ ALN and either Grade3 disease, or tumor size ≥ 5 cm, or Ki-67 ≥ 20%. GroupB: patients with stage IA-IIIC disease who did not meet those high risk criteria. TP (time from start to discontinuation of adjuvant ET) was compared between the 2 groups. Patients who had a gap of >90 days after their last date of ET, as documented in the EHR, were considered to have discontinued ET. Patients whose last ET was ≤90 days from Sept 2020 were censored. Cumulative incidence functions of nonpersistence were estimated, treating recurrences or deaths occurring during ET as competing risks. Results: While gender and race distributions were similar between groups, patients in GroupA (n=557) were younger and more likely to be premenopausal, have an ECOG PS score of 1 or 2+, and have received mastectomy, radiation and chemotherapy compared to GroupB (n=3471). Estimates of the cumulative incidence functions of nonpersistence were statistically different between the groups (p <.001). The Table shows the cumulative incidence (standard error) of nonpersistence at years 1-5 after initiating ET. Conclusions: This study suggests that patients at high risk of recurrence have higher ET-TP than those at lower risk. The separation was most pronounced at 5 years. The steep increase in 5-year nonpersistence in lower risk group could be due to a perception of less need to continue ET for longer periods of time in lower risk disease. The greater persistence in patients at high risk is noteworthy, but interventions to improve patient’s TP are still warranted. Table 1: Cumulative incidence of nonpersistence after initiating ET Citation Format: Kristin M. Sheffield, Alexandra S. Vitko, Jacqueline Brown. Persistence with adjuvant endocrine therapy in patients with early breast cancer at high risk of recurrence: a US-based real-world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-01.

Preventing metastatic recurrence in low-risk ER/PR + breast cancer patients—a retrospective clinical study exploring the evolving challenge of persistence with adjuvant endocrine therapy

PurposeIn the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients’ non-persistence with AET was performed.MethodsWomen who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. ‘Low risk’ was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test.ResultsWe identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028).ConclusionMetastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Attribution of symptoms to adjuvant endocrine therapy and association with adherence among older women with breast cancer: A qualitative study.

e24086 Background: Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality. However, adherence to AET is poor, with 1/3 of patients not completing the recommended 5-year treatment course. Studies have shown that symptoms of the medication, such as joint pain, hot flashes, and fatigue, are associated with AET discontinuation. While previous studies have focused on symptoms post-AET initiation, preliminary evidence suggests that pre-AET symptoms may be an important predictor of early AET discontinuation. We used qualitative interviews to explore adherence to AET and patients’ attribution of symptoms to AET to provide context for a larger quantitative study on the role of patient-reported distress pre-AET as a predictor of AET discontinuation. Methods: Participants were recruited from the Froedtert/MCW Cancer Center registry, stratified by high (≥4) and low pre-AET Distress Thermometer scores and adherence to/discontinuation of AET. Semi-structured phone interviews followed an interview guide focused on constructs previously identified in the literature as having strong associations with AET adherence. Interviews were recorded and transcribed. A multidisciplinary team developed a codebook based on the conceptual framework describing AET discontinuation by AlOmeir et al. as well as other themes that emerged from the data. Results: Interviews were conducted with 31 participants; ages ranged from 57-86 years. Participants were diverse with respect to race/ethnicity (55% white, 26% Black, 13% Latina, and 6% other racial/ethnic groups). Participants who reported symptoms described hot flashes, joint pain, low appetite, memory loss, depression, and fatigue. We saw support for previous findings by AlOmeir et al in which ability to deal with symptoms affected the decision to continue AET. We uncovered additional nuance related to attribution of symptoms, in that some participants attributed their symptoms to a side effect of AET, while others attributed symptoms to other factors including older age, recent completion of other cancer treatments, and psychological burden associated with a cancer diagnosis and treatment. Those who did not attribute symptoms to AET focused on AET as necessary treatment to increase survival, while those who attributed symptoms to AET reported a more negative AET experience in general, with AET described as an additional burden after cancer. Conclusions: Symptom attribution rather than experience of specific symptoms may be a key factor leading to discontinuation of AET. Patient-reported symptoms and associated distress pre-AET may be a viable way to identify patients at high-risk for AET nonadherence, allowing for timely intervention. This will be quantitatively tested in a large sample.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer

PurposeSide effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL).MethodsPatients aged ≥ 70 years with stage I–III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time.ResultsOverall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = − 4.37; 95% CI − 7.96 to − 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = − 11.10; 95% CI − 18.80 to − 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement.ConclusionA large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

SIOG2021-0050 - Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer

SIOG2021-0050 - Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer

Association of Modifiable Risk Factors With Early Discontinuation of Adjuvant Endocrine Therapy

Early discontinuation of adjuvant endocrine therapy (ET) is problematic among breast cancer survivors, with previous studies suggesting that up to 50% of women do not adhere to the recommended full 5 years of ET treatment. To identify the association between early discontinuation of ET in the Trial Assigning Individualized Options for Treatment (TAILORx) and modifiable risk factors, polypharmacy, and types of additional medications such as antidepressants and opioids. This post hoc analysis includes a subgroup of 954 patients with breast cancer in TAILORx, a randomized clinical trial conducted from April 7, 2006, to October 6, 2010. All participants received a diagnosis of hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer and started ET within a year of study entry. Analyses were conducted in the intent-to-treat population. Statistical analysis took place from January 15, 2020, to April 6, 2021. Participants completed measures on cancer-related health-related quality of life including physical well-being and social well-being prior to initiating ET. Early discontinuation of ET was defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence. Kaplan-Meier estimates were used to calculate discontinuation, and Cox proportional hazards regression joint prediction models were used to analyze the association between rates of adherence to ET with patient-level factors. A total of 954 women (mean [SD] age, 56.6 [8.9] years) were included in this analysis. In a joint model, receipt of chemoendocrine therapy (vs receipt of ET only; hazard ratio [HR], 0.57; 95% CI, 0.35-0.92; P = .02) and age older than 40 years (vs ≤40 years; HR for 41-50 years, 0.39; 95% CI, 0.18-0.85; P = .02; HR for 51-60 years, 0.28; 95% CI, 0.13-0.60; P = .001; HR for 61-70 years, 0.40; 95% CI, 0.18-0.86; P = .02; and HR for >70 years, 0.23; 95% CI, 0.07-0.77; P = .02) were associated with a lower probability of early discontinuation of ET. Adjusted for these factors, a history of depression compared with no history of depression (HR, 1.82; 95% CI, 1.19-2.77; P = .005), worse physical well-being compared with better physical well-being (HR, 2.12; 95% CI, 1.30-3.45; P = .002), and worse social well-being compared with better social well-being (HR, 1.94; 95% CI, 1.20-3.13; P = .006) were individually and significantly associated with a higher probability of early discontinuation of ET. Only antidepressant use at study baseline was associated with early discontinuation (HR, 1.87; 95% CI, 1.23-2.84; P = .003). In this post hoc analysis of a randomized clinical trial, baseline patient-reported health-related quality of life components, such as poor social well-being, poor physical well-being, and comorbid depression, were significant risk factors for early discontinuation of endocrine therapies. These results support systematic screening for patient-reported outcomes and depressive symptoms to identify women at risk for discontinuation of ET. ClinicalTrials.gov Identifier: NCT00310180.

Early discontinuation to adjuvant endocrine therapy in the ECOG-ACRIN TAILORx Trial.

7004 Background: The TAILORx study demonstrated women with an intermediate Oncotype DX score receive the same benefit with endocrine therapy (ET) compared to chemoendocrine therapy (CET). However, early discontinuation of adjuvant ET is problematic among breast cancer survivors, with previous studies suggesting that up to 50% of women do not adhere to the full 5 years of recommended ET treatment. The aim of this study was to identify patient-level risk factors associated with early discontinuation of ET in the TAILORx study. Methods: TAILORx was coordinated by the ECOG-ACRIN Cancer Research Group. Participants were a subgroup of 954 women who completed additional measures on health-related quality of life (HRQoL) including endocrine symptoms (ES) physical well-being (PWB) and social well-being (SWB) prior to initiating ET, which categorized into three groups by tertile for analysis. All participants were diagnosed with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer who started ET within a year of study entry. Early discontinuation of ET, defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence, was assessed by clinician report. Rate of discontinuation was calculated using Kaplan-Meier estimates, and Cox-proportional hazards joint models were used to analyze the association between rates of adherence to ET with patient-level factors. Results: In a joint model, receipt of CET therapy (vs receipt of ET only; HR = .59, 95% CI .38-.94, p = .02) and age above 40 (versus age &lt; = 40; HR = .30, 95% CI .14-.66, p = .003) were associated with a lower probability of early discontinuation of ET. Adjusted for these factors, a history of depression compared to no history of depression (HR 1.82, 95% CI 1.19-2.77, p = 0.005), worse ES compared to better ES (HR 1.70, 95% CI 1.06-2.74, p = 0.03), worse PWB compared to better PWB (HR 2.12, 95% CI 1.30-3.45,p = 0.003), and worse SWB compared to better SWB (HR 1.94, 95% CI 1.20-3.13, p = 0.007) were individually and significantly associated with a higher probability of early discontinuation of ET, although none reached statistical significance when all were included in a joint model. Conclusions: Younger women are at risk for early discontinuation and modifiable characteristics such as HRQoL and history of depression are potential risk factors for early discontinuation of ET. These results support systematic screening for HRQoL and depressive symptoms to identify women at risk for discontinuation of ET. Clinical trial information: NCT00310180 .

Abstract PD10-07: Patient reported outcomes and early discontinuation of adjuvant endocrine therapy according to neighborhood poverty rate

Abstract Introduction: Early discontinuation (DC) of adjuvant endocrine therapy (AET) for hormone receptor positive breast cancer (BC) is associated with increased risk of recurrence and death. Symptoms and low socioeconomic status (SES) have both previously been associated with early AET DC. Prospective collection of patient-reported outcomes (PRO) is increasingly used in oncology practice, and can lead to improvements in quality of life and survival in advanced cancer. Compared to patients of high SES, those of low SES report higher symptom burden in multiple clinical settings. Whether PRO reporting during AET differs according to SES is unknown. Methods: We enrolled women initiating AET for stage 0-III BC in a prospective clinic-based cohort from March 2012 to Dec 2016. At baseline (BL), 3, 6, 12, and 24 months (mo), participants completed these PROs online: FACT-ES, MOS Sexual Problems, and NIH PROMIS measures for pain interference, fatigue, depression, anxiety, physical function and sleep disturbance. Neighborhood poverty (NP) rate, a surrogate for SES based on US Census estimates of the % of persons in a zip code below the federal poverty line, was categorized as 0-5% (low), &amp;gt;5-10% (moderate) and &amp;gt;10% (high). We assessed AET DC and cited reason for DC by chart review. Baseline characteristics were compared between NP groups using Fisher’s exact and t-tests. Changes in mean PRO scores from BL to follow-up (FU) time points for each NP group were estimated simultaneously from a linear mixed effects regression model with a random intercept for each patient. We evaluated differences in changes in mean scores for all 8 PRO measures over time according to NP group with an interaction test. Statistical significance of p &amp;lt; 0.05/8 = 0.006 was used, adjusting for multiple comparisons. Results: Among 320 women, mean age was 61 (range 26-90), 83% were White, 10% Black, 65% were post-menopausal and 84% had Stage I-II BC. NP categorization was: 97 (30.3%) low, 127 (39.7%) moderate and 96 (30%) high. Mean stage distribution, and proportions of participants who had mastectomy, chemotherapy and radiation did not differ by NP group. There were fewer post-menopausal women in the moderate/high NP groups (61%) compared to the low NP group (72%, p=0.04). The proportion of Black participants increased with NP group (low 5%, moderate 10%, high 16%, p=0.04). Overall, 180 (56%) were on an aromatase inhibitor (AI) and 140 (44%) were on tamoxifen. There was more AI use in the low NP group (64%) compared to the moderate/high NP groups (53%, p=0.08). At BL, there were no differences in mean score on any PRO by NP group. For all NP groups, endocrine symptoms worsened at all FU times (all p&amp;lt;0.05) and physical function improved at most FU times. Compared to BL, mean changes in pain interference over time differed by NP group (interaction p=0.005), with less pain interference at 6 and 12 mo in the moderate/high NP groups and no significant change in the low NP group. Mean changes in other PROs did not differ by NP group. At median FU of 41 mo (range 3-75), the proportion of participants who discontinued AET due to side effects/intolerance was similar across NP groups (low 12.6%, moderate 16%, high 17%, p=0.67). Discussion: We found that changes in PROs during AET were similar across SES based on NP rates with the exception of less reported pain interference over time in participants of lower SES. The lack of improvement in pain interference in participants of higher SES may be attributable to arthralgias due to more frequent AI use. Despite differences in pain interference, early DC of AET due to side effects/intolerance did not differ by SES in this cohort. Our findings suggest that PROs are generally similar among early BC patients of varied SES receiving AET and that factors other than symptoms may explain the previously reported association between early DC and low SES. Citation Format: Ramy Sedhom, Amanda Blackford, David Lim, Jennifer Ensminger, Claire Snyder, Vered Stearns, Karen Lisa Smith. Patient reported outcomes and early discontinuation of adjuvant endocrine therapy according to neighborhood poverty rate [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 PD10-07.

Adjuvant endocrine therapy for breast cancer patients: impact of a health system outreach program to improve adherence.

Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET. We assembled a retrospective cohort of all KPNC patients diagnosed with HR+, stage I-III BC initiating AET before (n = 4287) and after (n = 3580) implementation of the outreach program. We compared adherence proportions and discontinuation rates before and after program implementation, both crude and adjusted for age, race/ethnicity, education, income, and stage. We conducted a pooled analysis of data from six Cancer Research Network (CRN) sites that had not implemented programs for improving AET adherence, using identical methods and time periods, to assess possible secular trends. In the pre-outreach period, estimated adherence in years 1, 2, and 3 following AET initiation was 75.2%, 71.0%, and 67.3%; following the outreach program, the estimates were 79.4%, 75.6%, and 72.2% (p-values < .0001 for pairwise comparisons). Results were comparable after adjusting for clinical and demographic factors. The estimated cumulative incidence of discontinuation was 0.22 (0.21-0.24) and 0.18 (0.17-0.19) at 3 years for pre- and post-outreach groups (p-value < .0001). We found no evidence of an increase in adherence between the study periods at the CRN sites with no AET adherence program. Adherence and discontinuation after AET initiation improved modestly following implementation of the outreach program.

3365 Treatment Interruptions and Early Discontinuation of Hormone Therapy in Hormone Receptor-Positive Breast Cancer Patients

OBJECTIVES/SPECIFIC AIMS: (1) To evaluate the association of patient and clinical factors with adherence to adjuvant hormone therapy (HT). (2) To examine the association of HT-related symptoms and the extent of remediation with early discontinuation of hormone therapy. METHODS/STUDY POPULATION: Retrospective cohort study of risk factors for interruption and early discontinuation of adjuvant hormone therapy in hormone receptor-positive nonmetastatic breast cancer patients diagnosed between 2009 and 2015. This study will include incident hormone receptor-positive breast cancer patients who initiated their HT and were followed at Tufts MC until Dec 31, 2016. Primary data source is electronic medical records (EMRs) RESULTS/ANTICIPATED RESULTS: The primary outcome of this study is early discontinuation to HT, defined as the first treatment gap of greater than or equal to 180 days following the initiation of HT. Treatment interruption, defined as any patient- or provider-initiated treatment gap of ≥ 2 weeks, will be examined as the secondary endpoint. Any HT-related symptoms occurred during a follow-up interval will be captured and categorized into five major types (i.e., vasomotor, neuropsychological, gastrointestinal, gynecological, and musculoskeletal symptoms). Onset and duration of a HT-related symptom will be recorded. Severity of the symptoms will also be rated by clinical oncologists. Remediations in response to HT- related symptoms will be collected and categorized into to two groups (pharmacological or non-pharmacological) and whether they were patient- or provider-initiated. Response to a remediation is defined as complete relief, partial relied, no relief, or with worsening symptoms. Response to a treatment change (i.e., HT switch or hold) was collected separately but using the same criteria. Analyses will be performed on the association between patient and clinical factors with rates of nonadherence (unplanned treatment interruption and/or early discontinuation) of hormone therapy, respectively. We also will explore whether patients with elevated symptoms and/or incomplete remediation will have earlier discontinuation of hormone therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Through formal chart review, we will establish a dataset that contains highly detailed information about treatment-emergent symptoms and remediations, which will enable us to quantitatively assess the impact of these treatment factors on adherence to hormone therapy for breast cancer. The in-depth analysis of risk factors associated with nonadherence to hormone therapy will inform development of interventions to improve cancer outcomes.

Discontinuation of adjuvant hormone therapy among breast cancer patients not previously attending mammography screening

BackgroundBreast cancer patients who have not previously attended mammography screening may be more likely to discontinue adjuvant hormone therapy and therefore have a worse disease prognosis.MethodsWe conducted a population-based cohort study using data from Stockholm Mammography Screening Program, Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and Swedish Cause of Death Register. Women in Stockholm who were diagnosed with breast cancer between 2001 and 2008 were followed until December 31, 2015. Non-participants of mammography screening were defined as women who, prior to their breast cancer diagnosis, were invited for mammography screening but did not attend.ResultsOf the 5098 eligible breast cancer patients, 4156 were defined as screening participants and 942 as non-participants. Compared with mammography screening participants, non-participants were more likely to discontinue adjuvant hormone therapy, with an adjusted hazard ratio (HR) of 1.30 (95% CIs, 1.11 to 1.53). Breast cancer patients not participating in mammography screening were also more likely to have worse disease-free survival, even after adjusting for tumor characteristics and other covariates (adjusted HR 1.22 (95% CIs, 1.05 to 1.42 for a breast cancer event).ConclusionsTargeted interventions to prevent discontinuation of adjuvant hormone therapy are needed to improve breast cancer outcomes among women not attending mammography screening.

Patient-reported outcomes and factors associated with early discontinuation of adjuvant endocrine therapy in premenopausal women with breast cancer

Background: Adjuvant endocrine therapy (AET) reduces risks of recurrence and death in women with hormone receptor-positive breast cancer (BC). Despite these benefits, many women discontinue AET prematurely due to symptoms. We have previously demonstrated associations between patient-reported outcomes (PRO) and clinical characteristics with early discontinuation (DC) in a clinic-based cohort. Here, we report PRO and factors associated with early DC among the premenopausal participants.

Abstract P6-08-20: Non-adherers of mammography screening: Delayed surgery, early discontinuation of adjuvant hormone therapy, and worse breast cancer outcomes

Abstract Purpose: To test the hypothesis that prior non-adherence to mammography screening could predict subsequent non-adherence to breast cancer treatment. Specifically, we hypothesized that as compared with adherers, screening non-adherers may be more likely to have delayed surgery, discontinue their adjuvant hormone therapy, and consequently have worse breast cancer outcomes. Methods: We conducted a record-linkage study based on data from the Stockholm Mammography Screening Program (1989-2013), Stockholm-Gotland Breast Cancer Register (2001-2017), Swedish Prescribed Drug Register (2005-2017), and Cause of Death Register (2001-2013). Women diagnosed with breast cancer between 2001 and 2008 in Stockholm, Sweden, were prospectively followed for treatment and survival until December 31st, 2013 (N=5106). Screening non-adherers were defined as patients who were invited but did not attend the screening mammography within 2 years before breast cancer diagnosis. Discontinuation of adjuvant hormone therapy was defined as having any interval between two consecutive dispenses exceeding 180 days during follow-up. Disease-free survival was defined as time to local recurrence, distant metastasis, contralateral breast cancer, or death from breast cancer, whichever came first. Results: The proportion of delayed surgery (≥6 weeks) for screening adherers (restricted to interval cancers only) versus non-adherers were 15.5% versus 20.6%, respectively (P&amp;lt;0.01). As compared with adherers, screening non-adherers were more likely to discontinue their adjuvant hormone therapy, with an adjusted hazard ratio of 1.37 (95% CI, 1.17 to 1.61). Furthermore, Cox regression analysis showed that screening non-adherence was associated with poorer disease-free survival even after adjusting for tumor characteristics and other covariates, with an adjusted hazard ratio of 1.19 (95% CI, 1.01 to 1.41) for screening non-adherers versus adherers. Screening AdherersScreening Non-adherers Univariable-analysisMultivariable analysis#Delayed surgery&amp;gt;6 weeks* No897(84.5)624(79.4) 1.00 (Reference)1.00(Reference)Yes†165(15.5)162(20.6) 1.40(1.10-1.78)1.34(1.05-1.72)Discontinuation of adjuvant hormone therapy** No822(50.3)145(42.7) 1.00(Reference)1.00(Reference)Yes††812(49.7)195(57.3) 1.33(1.14-1.56)1.37(1.17-1.61)Disease free survival events No3574(85.8)752(79.8) 1.00(Reference)1.00(Reference)Yes††590(14.2)190(20.2) 1.46(1.24-1.72)1.19(1.01-1.41)* Restricted to patients diagnosed with clinically detected cancers who were primary operated without neoadjuvant therapy; ** Restricted to patients diagnosed after July 1st, 2005, who initiated adjuvant hormone therapy.† Odds ratios (95% CI);† † Hazard ratios (95% CI).# Adjusting for age, tumor size, lymph node involvement, estrogen receptor status, progesterone receptor status, HER2 status, and type of surgery Conclusions: Compared to adherers, screening non-adherers are more likely to have delayed surgery, discontinue their adjuvant hormone therapy, and subsequently have worse breast cancer outcomes even after adjusting for baseline tumor characteristics. Citation Format: He W, Bergman LE, Törnberg S, Strand F, Hall P, Czene K. Non-adherers of mammography screening: Delayed surgery, early discontinuation of adjuvant hormone therapy, and worse breast cancer outcomes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-20.