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Purpose: Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality; however, adherence is suboptimal. Interventions exist, yet few have improved adherence. Patient characteristics may alter uptake of an intervention to boost adherence. We examined moderators of the effect of a virtual intervention (STRIDE; #NCT03837496) on AET adherence after breast cancer. Methods: At a large academic medical center, patients taking AET (N = 100; Mage = 56.1, 91% White) were randomized to receive STRIDE versus medication monitoring. All stored their medication in digital pill bottles (MEMS Caps) which captured objective adherence. Participants self-reported adherence (Medication Adherence Report Scale) at 12 weeks post-baseline. Moderators included age, anxiety, and depressive symptoms (Hospital Anxiety and Depression Scale), AET-related symptom distress (Breast Cancer Prevention Trial Symptom Scale), and AET-specific concerns (Beliefs about Medications Questionnaire). We used hierarchical linear modeling (time × condition × moderator) and multiple regression (condition × moderator) to test the interaction effects on adherence. Results: Age (B = 0.05, SE = 0.02, p = 0.003) and AET-related symptom distress (B = −0.04, SE = 0.02, p = 0.02) moderated condition effect on self-reported adherence while anxiety (B = −1.20, SE = 0.53, p = 0.03) and depressive symptoms (B = −1.65, SE = 0.65, p = 0.01) moderated objective adherence effects. AET-specific concerns approached significance (B = 0.91, SE = 0.57, p = 0.12). Participants who received STRIDE and were older or presented with lower anxiety and depressive symptoms or AET-related symptom distress exhibited improved adherence. Post hoc analyses revealed high correlations among most moderators. Conclusions: A subgroup of patients who received STRIDE exhibited improvements in AET adherence. The interrelatedness of moderators suggests an underlying profile of patients with lower symptom burden who benefitted most from the intervention. Study registration: NCT03837496. [ABSTRACT FROM AUTHOR]

Purpose: In 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. Methods: Women 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. Results: We 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). Conclusion: Metastatic 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. [ABSTRACT FROM AUTHOR]

Purpose: In 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. Methods: Women 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. Results: We 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). Conclusion: Metastatic 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. [ABSTRACT FROM AUTHOR]

Purpose: Characterizing oral adjuvant endocrine therapy (ET) non-initiation and non-persistence in young women with breast cancer can inform strategies to improve overall adherence in this population. Methods: We identified 693 women with hormone receptor-positive, stage I–III breast cancer enrolled in a cohort of women diagnosed with breast cancer at age ≤ 40 years. Women were classified as non-initiators if they did not report taking ET in the 18 months after diagnosis. Women who initiated but did not report taking ET subsequently (through 5-year post-diagnosis) were categorized as non-persistent. We assessed ET decision-making and used logistic regression to identify factors associated with non-initiation/non-persistence and to evaluate the association between non-persistence and recurrence. Results: By 18 months, 9% had not initiated ET. Black women had higher odds and women with a college degree had lower odds of non-initiation. Among 607 women who initiated, 20% were non-persistent. Younger age, being married/partnered, and reporting more weight problems were associated with higher odds of non-persistence; receipt of chemotherapy and greater hot flash and vaginal symptom burden were associated with lower odds of non-persistence. Adjusting for age and clinical characteristics, non-persistence was associated with lower odds of recurrence. Women who initiated were more likely to report shared decision-making than non-initiators (57% vs. 38%, p = 0.049), while women who were non-persistent were less likely to indicate high confidence with the decision than women who were persistent (40% vs. 63%, p < 0.001). Conclusion: Interventions to improve ET decision-making may facilitate initiation and address barriers to adherence in young breast cancer survivors. Trial registration: www.clinicaltrials.gov, NCT01468246. [ABSTRACT FROM AUTHOR]

Purpose: Sexual function problems are common but under-reported among women receiving adjuvant endocrine therapy for breast cancer. Worsening scores on patient-reported outcomes (PROs) may identify those at risk for sexual function problems during treatment. We performed a secondary analysis of prospectively collected PROs in women receiving adjuvant endocrine therapy to identify factors associated with worsening sexual function. Methods: Women with stage 0–III breast cancer initiating adjuvant endocrine therapy participating in a prospective cohort completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Sexual function was evaluated by the MOS-SP measure. Other measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance and the Endocrine Symptom Subscale of the FACT-ES. We evaluated associations between score worsening of at least the minimal important difference (MID) in PROMIS T-scores (4 points) and FACT-ES scores (5 points) with score worsening of at least the MID in MOS-SP scores (8 points) using logistic regression. Results: Among 300 participants, 45.7% experienced ≥ 8-point worsening of MOS-SP score at any time point compared to baseline. Worsening endocrine symptoms (OR 1.34, 95% CI 1.22–1.49, p < 0.001), worsening physical function (OR 1.09, 95% CI 1.00–1.18, p = 0.06), and prior mastectomy (OR 1.45, 95% CI 0.94–2.23, p = 0.09) were associated with MOS-SP score worsening by at least the MID. Conclusion: Worsening endocrine symptoms and physical function identified on PROs are associated with worsening sexual function during adjuvant endocrine therapy. Routine assessment of these domains with PROs may identify women at risk for sexual function problems. Trial registration number: NCT01937052; Date of Registration: 09/09/2013. [ABSTRACT FROM AUTHOR]

Purpose: To identify a structure to explain the relationship between socio-clinico factors, necessity-concerns beliefs, and perceived barriers to adherence with adjuvant endocrine therapy (AET) amongst women with breast cancer. Methods: Participants were 244 patients with early-stage breast cancer recruited from two tertiary hospitals from May 2015 to December 2018 who completed questionnaires on medication adherence (Simplified Medication Adherence Questionnaire), necessity-concerns beliefs (Beliefs about Medicine Questionnaire), and barriers to adherence (Adherence Starts with Knowledge Questionnaire). Socio-clinico variables were collected via interview and medical records review. Structural equation modelling was applied to examine the relationships between these variables and possible mediating effects of necessity-concerns beliefs on adherence to AET. Results: The median age of the study participants was 61 (range 32–80) years and the median duration on AET was 1.6 (IQR 1.2–2.6) years. Adherence was positively associated with age (β = 0.145, 95% CI: 0.011 to 0.279, p = 0.034) and negatively associated with barriers (β = − 0.381, 95% CI: − 0.511 to − 0.251, p < 0.001). There was no effect of Necessity (β = 0.006, 95% CI: − 0.145 to 0.158, p = 0.933) or Concerns (β = 0.041, 95% CI: − 0.117 to 0.199, p = 0.614) on adherence. Necessity-concerns beliefs were also not significant mediators in the relationship between socio-clinico factors and medication adherence. Conclusions: Older age and lower barriers to adherence were associated with higher adherence scores. Necessity-concerns beliefs did not have a significant effect on adherence as majority of the patients identified forgetfulness as a reason for non-adherence. [ABSTRACT FROM AUTHOR]

Background: Compared to tamoxifen, adjuvant treatment with aromatase inhibitors improves disease outcomes of postmenopausal women with hormone receptor-positive early breast cancer. In the international, randomized, double-blind BIG 1-98 trial, 8010 women were randomized to receive tamoxifen, letrozole, or sequential use of the agents for 5 years. With a focus on switching between agents, we investigated cardiovascular events over the entire 5-year treatment period. Methods: Of the 6182 patients enrolled, 6144 started trial treatment and were included in this analysis. Adverse events occurring during study treatment until 30 days after cessation were considered. Eight cardiovascular event types were defined. Cumulative incidence of events were estimated using the Kaplan–Meier method, without consideration for competing events. Multivariable Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI) for pairwise comparisons of treatment arms. Results: While on study treatment, 6.5% of patients (n = 397) had any cardiac events reported; for 2.4%, the event was grades 3–5, of which 11 (0.2%) were grade 5. Letrozole monotherapy was associated with higher risk of grade 1–5 ischemic heart disease (HR = 1.81; 95% CI, 1.06–3.08) compared with tamoxifen monotherapy. Patients assigned sequential tamoxifen →letrozole (HR = 1.59; 95% CI, 0.92–2.74) or sequential letrozole → tamoxifen (HR = 1.20; 95% CI, 0.68–2.14) showed a lesser degree of risk elevation. Patients assigned to tamoxifen-containing regimens had significantly higher risk of grade 1–5 thromboembolic events (tamoxifen monotherapy HR = 2.10; 95% CI, 1.42–3.12; tamoxifen → letrozole HR = 1.96; 95% CI, 1.32–2.92; letrozole → tamoxifen HR = 1.56; 95% CI 1.03–2.35) as compared with patients assigned letrozole alone. Conclusion: When initiating or switching between adjuvant endocrine treatments in postmenopausal patients, age and medical history, with special attention to prior cardiovascular events, should be balanced with expected benefit of the treatment. [ABSTRACT FROM AUTHOR]

Purpose: The CALGB 9343 trial demonstrated that women age 70 or older with early-stage, estrogen receptor positive (ER +) breast cancer (BC) may safely forgo radiation therapy (RT) and be treated with breast conserving surgery followed by adjuvant endocrine therapy (AET) alone. However, most patients in this population still undergo RT in part because AET adherence is low. We sought to develop a predictive model for AET initiation and adherence in order to improve decision-making with respect to RT omission. Methods: Women ages 70 and older with early-stage, ER + BC were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidities, socioeconomic measures, prescription medications, and demographics were collected as potential predictors. Bivariate analysis was performed to identify factors associated with AET initiation and adherence. Stepwise selection of significant predictors was used to develop logistic regression classifiers for initiation and adherence. Model performance was evaluated using the c-statistic and other measures. Results: 11,037 patients met inclusion criteria. Within the cohort, 8703 (78.9%) patients initiated AET and 6685 (60.6%) were adherent to AET over 1 year. Bivariate predictors of AET initiation were similar to predictors of adherence. The best AET initiation and adherence classifiers were poorly predictive with c-statistics of 0.65 and 0.60, respectively. Conclusions: The best models in the present study were poorly predictive, demonstrating that the reasons for initiation and adherence to AET are complex and individual to the patient, and therefore difficult to predict. Initiation and adherence to AET are important factors in decision-making regarding whether or not to forgo adjuvant RT. In order to better formulate treatment plans for this population, future work should focus on improving individual prediction of AET initiation and adherence. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant endocrine therapy (AET) for ≥ 5 years is generally recommended for women with hormone receptor-positive breast cancer to reduce cancer recurrence/mortality; however, adherence can be suboptimal. We tested determinants of AET adherence using patient characteristics, treatment pathways, AET initiation timing, and multiple healthcare facility use. An underlying objective was to explore how oncological pathways mirror chronic disease management to monitor adherence and target improvement interventions using administrative datasets. Methods: Using patient-linked administrative health data from the Italian Lombardy Region, we identified 33.291 surviving patients starting AET in 2010–2016, with two (22.939 patients) or five years (8400 patients) follow-up, using a ≥ 80% prescription refill approach to measure adherence and logistic regression to test determinants of adherence. Results: AET crude adherence falls significantly during follow-up, from 94% at 1 Year to 58% at 5 Years. At 5 Years, patients who were older (>70), prescribed tamoxifen-only (OR 0.69; 95% CI 0.57–0.83; p = 0.0001) vs. aromatase inhibitors-only or therapy switches, treated for depression (OR 0.68; 95% CI 0.60–0.78; p < 0.0001), with surgery performed in high-volume hospitals (OR 0.85; 95% CI 0.75–0.97; p = 0.0116) showed lower adherence. Loyalty, or continued care in the surgical hospital (OR 1.73; 95% CI 1.51–2.00; p < 0.0001), undergoing chemotherapy before AET (OR 2.65; 95% CI 2.02–3.48; p < 0.0001), and earlier AET initiation, positively influenced adherence. Conclusions: Chronic disease monitoring using administrative data can help oncologists focus efforts to ensure AET adherence. Results suggest addressing mental health, age, disease severity patient perceptions, timely AET initiation and therapy switches, and encouraging continued follow-up in the same hospital or better care coordination with outside follow-up specialists. [ABSTRACT FROM AUTHOR]

Purpose: Despite the benefits of adjuvant endocrine therapy (AET) for reducing recurrence and mortality risks after hormone-sensitive breast cancer, AET adherence is sub-optimal for a high proportion of women. However, little is known about long-term patterns of AET adherence over the minimally recommended 5 years. Our objectives were to: (1) identify 5-year AET adherence trajectory groups; (2) describe trajectory groups according to adherence measures traditionally used (i.e., Proportion of Days Covered); and (3) explore factors associated with trajectories. Methods: We conducted a 5-year cohort study using data from a French national study that included AET dispensing data. Women diagnosed with first non-metastatic breast cancer and having at least 1 AET dispensing in the 12 months after diagnosis were included. Group-based trajectory modeling was used to identify adherence trajectory groups by clustering similar patterns of monthly AET dispensing. Multinomial logistic regressions were used to identify factors associated with trajectories. Results: Among 674 women, five AET adherence trajectory groups were identified: (1) quick decline and stop (5.2% of women); (2) moderate decline and stop (6.4%); (3) slow decline (17.2%); (4) high adherence (30.0%); and (5) maintenance of very high adherence (41.2%). Mean 5-year Proportion of Days Covered varied from 10 to 97% according to trajectories. Women who did not receive chemotherapy or a personalized care plan were more likely to belong to trajectories where AET adherence declined and stopped. Conclusion: Our results provide information on the diversity of longitudinal AET adherence patterns, the timing of decline and discontinuation and associated factors that could inform healthcare professionals. [ABSTRACT FROM AUTHOR]

Purpose: Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5 years 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. Methods: 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. Results: 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. Conclusion: Adherence and discontinuation after AET initiation improved modestly following implementation of the outreach program. [ABSTRACT FROM AUTHOR]

Background: Endocrine therapy with aromatase inhibitors (AIs) is the cornerstone of adjuvant systemic treatment for postmenopausal patients with hormone receptor-positive breast cancer. It has become clear that hormone receptor-positive breast cancer carries a consistent risk of relapse up to 15 years after diagnosis. Extended duration of adjuvant AIs therapy after completing initial standard adjuvant AIs-containing therapy may prevent late recurrence and death. We performed a meta-analysis to assess the real impact of the extended adjuvant therapy with AIs. Methods: A literature-based meta-analysis of the randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, Embase, Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. The endpoints were disease-free survival (DFS), overall survival (OS), local recurrence, distant recurrence, contralateral breast cancer, non-breast cancer-related death, and toxicity. Results: Eight trials comprising 15,966 patients met the inclusion criteria. The pooled analysis revealed a significant improvement in DFS (RR = 0.79; 95% CI 0.68–0.91), distant recurrence (RR = 0.75; 95% CI 0.58–0.96), and contralateral breast cancer (RR = 0.53; 95% CI 0.40–0.70) in the extended AIs group. While there was not significant improvement in OS (RR = 1.00, 95% CI 0.99–1.01), non-breast cancer-related death (RR = 1.16, 95% CI 0.96–1.41), and local recurrence (RR = 0.82; 95% CI 0.64–1.06), the subgroup analysis showed that the patient with tumor size > 2 cm (HR = 0.74, RD = − 0.31, P = 0.05 vs. HR = 0.85, RD = − 0.16, P = 0.20), node positive status (HR = 0.77, RD = − 0.27, P = < 0.0001 vs. HR = 0.89, RD = −0.12, P = 0.19) and previous chemotherapy use (HR = 0.75, RD = − 0.29, P = 0.003 vs. HR = 0.91, RD = −0.10, P = 0.44) would get a greater DFS benefit with extended AIs. Longer treatment with AIs was associated with an increased risk ratio of bone pain (RR = 1.26, RD = 0.04, P = 0.003), bone fractures (RR = 1.59, RD = 0.02, P = 0.002), osteoporosis (RR = 1.53, RD = 0.07, P = 0.005), myalgia (RR = 1.26, RD = 0.04, P = 0.02), and treatment discontinuation for adverse events (RR = 1.51, RD = 0.06, P = 0.0009). Conclusion: After initial standard AIs-containing adjuvant therapy, extended AIs therapy could further bring a DFS benefit for postmenopausal patients with early breast cancer, especially in the patients with high-risk characteristics. [ABSTRACT FROM AUTHOR]

Objective: To assess adherence to endocrine therapy and its relation to recurrence and mortality in women with early breast cancer. Methods: This is a retrospective cohort study in population-based cancer registries in two Catalonian provinces of Spain. We included all cases of invasive stage I–III breast cancer diagnosed from 2007 to 2011 and with follow-up to 2017. Adherence to endocrine therapy was measured by means of prescription refills. Patients were considered non-adherent if they filled less than 80% of their prescriptions. After collecting data from patients' medical records, we analysed clinical variables and their relation with adherence by means of logistic and Cox regression models. Results: The study included 2413 women. Five-year adherence was 84.5%; the greatest risk for non-adherence was in women under 50 years of age, diagnosed with stage III cancer, treated with neoadjuvant therapy, or receiving tamoxifen or sequential treatment. Adverse effects were associated with greater adherence. Non-adherence was significantly and independently associated with recurrence (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.16–2.51) and all-cause mortality (HR 2.11, 95% CI 1.62–2.74), after adjusting for age and tumour stage. Conclusions: Although non-adherence was relatively infrequent in this population-based study, its impact on the risk of recurrence and mortality was considerable. Clinicians should make efforts to ensure therapeutic adherence during clinical follow-up of women with breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated associations between personal and clinical social support and non-adherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network.Methods: This study included 3382 women from the Pathways Study diagnosed from 2005 to 2013 with stages I-III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately 2 months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and non-initiation (< 2 consecutive prescription fills within a year after diagnosis). Among those who initiated treatment, we used proportional hazards regression to evaluate associations with discontinuation (≥ 90 day gap) and non-adherence (< 80% medical possession ratio).Results: Of those who initiated AET (79%), approximately one-fourth either discontinued AET or were non-adherent. AET non-initiation was more likely in women with moderate (adjusted OR 1.18, 95% CI 0.96-1.46) or low (OR 1.30, 95% CI 1.05-1.62) versus high personal social support (P trend = 0.02). Women with moderate (HR 1.20, 95% CI 0.99-1.45) or low (HR 1.32, 95% CI 1.09-1.60) personal social support were also more likely to discontinue treatment (P trend = 0.01). Furthermore, women with moderate (HR 1.25, 95% CI 1.02-1.53) or low (HR 1.38, 95% CI 1.12-1.70) personal social support had higher non-adherence (P trend = 0.007). Associations with clinical social support and outcomes were similar. Notably, high clinical social support mitigated the risk of discontinuation when patients’ personal support was moderate or low (P value = 0.04).Conclusions: Women with low personal or clinical social support had higher AET non-adherence. Clinician teams may need to fill support gaps that compromise treatment adherence. [ABSTRACT FROM AUTHOR]

Background: Adjuvant endocrine therapy (AET) significantly reduces recurrence and mortality in women with breast cancer (BrCa). Despite the efficacy of AET in improving BrCa outcomes, up to 50% of women do not adhere to prescribed AET regimens. While numerous demographic and clinical predictors influence adherence and persistence, few studies have identified the patient-reported factors that influence AET adherence and persistence.Purpose: The aim was to examine the patient-reported personal, social, and structural factors influencing BrCa survivors’ adherence and persistence with AET.Methods: An integrative review was undertaken wherein PubMed, Medline, CINAHL, Embase, and PsycINFO databases were searched using keyword descriptors and database subject headings. Inclusion criteria included quantitative or qualitative peer-reviewed studies written in English that assessed AET adherence and/or persistence through objective measurement or self-report and included patient-reported factors found to influence adherence and/or persistence. The data extracted from eligible studies were entered into a matrix, and systematically compared and iteratively analyzed using relational autonomy as an organizing theoretical framework.Results: A total of 43 manuscripts (9 qualitative and 34 quantitative) were reviewed. Several personal, social, and structural factors were identified that influenced AET adherence and persistence, including side effects, necessity beliefs, self-efficacy, the patient–healthcare provider relationship, social support, and continuity of follow-up care.Conclusions: An increasing number of studies have focused on identifying the patient-reported factors that influence AET adherence and persistence. This review highlights important personal, social, and structural factors that act as facilitators and barriers in adhering to and persisting with long-term AET. Acknowledging and addressing these factors is key to providing women with the care needed to improve suboptimal adherence and persistence. [ABSTRACT FROM AUTHOR]

Purpose: To explore differences in opioid use across different adjuvant endocrine therapy (AET) regimens, factors associated with opioid use, and the impact of opioid use on overall survival in female breast cancer patients treated with AET. Methods: This retrospective study analyzed 2006-2012 SEER-Medicare datasets, following patients for at least two years from the index date, defined as the first date they filled an AET prescription. The study included adult women with incident, primary, hormone-receptor-positive, stage I-III breast cancer. They were also first-time AET users, and fee-for-service Medicare enrollees continuously enrolled in Medicare Parts A, B, and D. The main independent variable was the AET regimen. We measured whether patients used opioids after the initiation of AET. Results: After the adjustment of inverse probability treatment weights and unbalanced covariates, the average treatment effect probabilities of opioid use were similar between those who used aromatase inhibitors (AI) only and those used tamoxifen (TAM) only (56.2 vs. 55.3%, respectively). Opioid use probabilities for those who switched from AI to TAM were higher than those for the TAM-only and AI-only groups. Opioid use was also significantly associated with AET non-adherence. Opioid users had a significantly higher risk of death (adjusted hazard ratio [HR] = 1.59, p < 0.001). Conclusions: Switching from AI to TAM was associated with a high likelihood of opioid use. Opioid use was significantly associated with AET non-adherence and higher risk of mortality in female Medicare beneficiaries with breast cancer even after adjusting for adherence. [ABSTRACT FROM AUTHOR]

Purpose: Non-adherence/persistence to adjuvant endocrine therapy can negatively impact survival. Beliefs about medicines are known to affect adherence. This study aims to identify socio-demographic and clinical characteristics associated with medication beliefs among women taking aromatase inhibitors (AIs). Methods: Women completed an online survey on beliefs about AI therapy [Beliefs about Medicines Questionnaire (BMQ)], beliefs about breast cancer [Assessment of Survivor Concerns scale (ASC)], and depression [Personal Health Questionnaire depression scale (PHQ-8)]. Socio-demographic and clinical characteristics were collected. Bivariate analyses and linear regression models were performed to investigate relationships between variables. Results: A total of 224 women reported currently taking AI therapy and were included in the analysis. Significantly higher concern beliefs were found among women who had at least mild depression, experienced side effects from AIs, and previously stopped therapy with another AI. Significant correlations were found between concern and necessity beliefs and cancer and health worry. Women age 70 and older displayed less fear of cancer recurrence and health worry, and a trend towards lower necessity and concern beliefs. No differences were found for other variables. In the regression model, greater necessity beliefs were found with increases in the number of current prescription medications ( B = 1.06, 95% CI 0.31-1.81, p = 0.006) and shorter duration of current AI therapy ( B = −0.65, 95% CI −1.23 to −0.07, p = 0.029), whereas greater concern beliefs were associated with higher depression scores ( B = 1.19, 95% CI 0.35-2.03, p = 0.006). Conclusions: Medication necessity and concern beliefs were associated with a definable subset of patients who may be at higher risk for non-persistence. [ABSTRACT FROM AUTHOR]

Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifen-2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant ( p = 0.019, HR 0.729, 95 % CI 0.560-0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95 % CI 0.878-2.297; HR low IS 1.657, 95 % CI 1.131-2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95 % CI 1.375-4.495; HR low IS 2.422, 95 % CI 1.439-4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95 % CI 0.950-2.395; HR low IS 1.848, 95 % CI 1.277-2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population. [ABSTRACT FROM AUTHOR]

Five years of Tamoxifen (Standard TAM) is a common treatment option for early-stage, hormone receptor positive (HR+) breast cancer (BC). Extending Standard TAM by 5 additional years (Extended TAM) can improve survival and BC recurrences. In postmenopausal women, the use of extended aromatase inhibitors (Extended AI) after Standard TAM is an alternative to Extended TAM. This study examines the cost-effectiveness (CE) of extending Standard TAM with Extended TAM vs. Extended AI in postmenopausal HR+ early-stage BC patients. Three treatments were assessed: (1) Standard TAM; (2) Extended TAM; (3) Extended AI through a Markov model using a Canadian health system perspective, lifetime time-horizon, quality adjusted life years (QALYs), and a 5 % discount rate for future costs and utilities. Incremental cost-effectiveness ratios (ICERs) were calculated, and the impact of parameter uncertainty was assessed through probabilistic sensitivity analyses (SA) using conventional CE thresholds. The estimated total per person costs in 2012 Canadian dollars [$1.00 CAD = $0.99 US 2012] were the least for Extended TAM ($8,623 CAD) and most for Extended AI ($9,432 CAD). Extended AI was the most effective regimen, while Standard TAM was the least. Extended AI was cost-effective at conventional thresholds vs. Extended TAM (ICER: $3,402 CAD/QALY) which was robust to the SA. This study suggests that Extended AI and Extended TAM result in improved QALYs and lower healthcare costs vs Standard TAM. Extended AI results in the greatest improvement in QALYs and is the most cost-effective treatment alternative despite its higher drug costs. [ABSTRACT FROM AUTHOR]

To investigate whether the health-related quality of life (HRQOL) of patients switching from tamoxifen to anastrozole in a randomized trial is identical to that of those who continued tamoxifen after 1-4 years of adjuvant tamoxifen in Japanese postmenopausal breast cancer patients. Eligible patients for the randomized trial, the National Surgical Adjuvant Study of Breast Cancer 03, were recurrence-free postmenopausal women who had received definitive surgery for primary breast cancer with positive hormone receptor(s), and had been taking tamoxifen for 1-4 years postoperatively. They were randomly assigned to continue tamoxifen or to switch to anastrozole for a total duration of five years. Subjects were asked to reply to a self-administered QOL questionnaire survey to assess HRQOL (FACT-B [breast cancer scale], FACT-ES [endocrine symptom scale]) and psychological distress (CES-D: Center for Epidemiologic Studies Depression scale) at randomization (baseline), 3 months, 1, and 2 years after randomization, respectively. At baseline 694 patients (346 in the tamoxifen group and 348 in the anastrozole group) responded to the survey. The total scores of FACT-G, FACT-ES, and those of the FACT-G physical well-being subscale were statistically significantly better in the tamoxifen group than in the anastrozole group ( P = 0.042, 0.038, and 0.005, respectively). However, there was no statistically significant difference between the treatment groups in the CES-D scores. Continuation of tamoxifen treatment after adjuvant tamoxifen for 1-4 years may provide Japanese breast cancer patients with better HRQOL than by switching to anastrozole. [ABSTRACT FROM AUTHOR]

Observational studies on long-term endocrine treatment among breast cancer patients have presented discontinuation rates on tamoxifen, but lack information on the continuance of any endocrine treatment [both tamoxifen and aromatase inhibitors (AIs)] within the same cohort. In this study we determined switching rates from tamoxifen to AIs, discontinuation rates of tamoxifen only, discontinuation rates of any endocrine treatment and determinants of first treatment switch and treatment discontinuation. Patients with early stage breast cancer (stage I–IIIa) starting on tamoxifen were selected from the linked Eindhoven Cancer Registry-PHARMO RLS cohort in the period 1998–2006. Continuous use (allowing a 60 days gap between refills) of tamoxifen only and any endocrine treatment were determined after various follow-up periods: 1, 2, 3, 4, and 5 years. Time to first switch from tamoxifen to an AI was assessed. Cox regression was used to identify determinants of first treatment switch, discontinuation of tamoxifen, and discontinuation of any endocrine treatment. A total of 1,451 new early stage breast cancer patients started on tamoxifen. Of those, 380 had a treatment switch to an AI during follow-up. Of the patients followed for 5 years, 40% continuously used tamoxifen, which was 49% for any endocrine treatment. Older age (older than 70 versus 50–69 years) was independently associated with increased discontinuation of tamoxifen and any endocrine therapy. Patients with two or more concomitant diseases (versus no comorbidity) showed an increased likelihood to stop any endocrine treatment or switch treatment from tamoxifen to an AI. In conclusion, up to half of the breast cancer patients starting tamoxifen continued 5 years of endocrine treatment. Identification of patients at risk of discontinuation will assist in the development of interventions to improve treatment continuation comparable to that of patients included in clinical trials. [ABSTRACT FROM AUTHOR]

There are few studies of model-based survival projections using early empirical results for estimating long-term survival. Utilizing Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) data, a Markov model was generated to compare empirical results with those modeled beyond the empirical result time horizon in estrogen receptor (ER)-positive early-stage breast cancer (ESBC). Modeling 15-year survival based on 5- and 10-year EBCTCG data resulted in an average error estimate in breast cancer mortality of 0.75% [range −0.83 to 2.19%]. Although modeling life expectancy differences ranged from an underestimate of −7.93% to an overestimate of 12.64%, over the span of 15 years this corresponded to a loss of 18 days or a gain of 40 days of life. Reliable early survival data may be used to generate models that accurately estimate 15-year survival in ER-positive ESBC. Whether early survival data can be employed over the lifetime horizon remains to be demonstrated. [ABSTRACT FROM AUTHOR]

Among 834 patients who had primary breast cancer treated by surgery without adjuvant systemic therapy, 363 had relapse treated by endocrine therapy alone. Patients with oestrogen receptor positive tumours (median: 70 vs. 45 months, p<0.0001) or with non-progression at 6 months of therapy (median: 111 vs. 37 months, p<0.0001) survived longer than those with oestrogen receptor negative tumours or with disease progression respectively, presumably due to the effect of therapy. On the other hand, the median disease-free interval, uninfluenced by therapy, showed a similar difference: oestrogen receptor positive versus negative=29 versus 21 months, p<0.005; non-progression versus progression=40 versus 19 months, p<0.0001. Patients with oestrogen receptor-positive tumours and non-progression at 6 months had the longest disease-free interval. The present study has established that there are factors, other than the oestrogen receptor, inherent in the primary tumour as reflected by the disease-free interval, which affect hormone sensitivity. Selection of adjuvant endocrine therapy based on the oestrogen receptor alone would deem inadequate. Further studies to elucidate other possible factors are warranted to refine the use of endocrine therapy, especially in the adjuvant setting when no indication of response is available. [ABSTRACT FROM AUTHOR]

Potential effects of tamoxifen therapy on blood coagulation and fibrinolysis were investigated in women with breast cancer. We studied 14 parameters of hemostasis in 19 postmenopausal women receiving 20 mg tamoxifen/day as an adjuvant treatment. Blood sampling was done before and after the 1st, 3rd, and 6th month of treatment. Pretreatment values of procoagulation, anticoagulation, plasminogen, and plasminogen activator inhibitor were found within the reference range, whereas tissue-plasminogen activator, fibrin degradation products, and prothrombin-fragment 1+2 were elevated. On therapy an initial decrease of all measured parameters was observed. The effect was pronounced in coagulation inhibitors (antithrombin III, protein C and S). No pathological values (below 60%) were observed. No further effects were found during the 3rd and 6th month of treatment. Our data indicate that the decrease of hemostatic parameters during the initial phase of tamoxifen treatment is due to the timing of blood collection, which took place no more than 14 days after surgery. The reduction of coagulation inhibitors was not associated with pathological values. No cumulative effects were seen during tamoxifen therapy. The decrease was not associated with a concomittant increase of in vivo coagulation markers (prothrombin-fragment 1+2, thrombin-antithrombin-complex, fibrin degradation products). Therefore our results are likely to reflect only the resolution of postoperative activation and do not translate into a drug related thrombogenic effect. [ABSTRACT FROM AUTHOR]