Effects Of Adjuvant Endocrine Therapy Research Articles

Abstract LB_B07: Probability of negative impact on adherence caused by the most frequent side effects of adjuvant endocrine therapy for premenopausal breast cancer in SOFT and TEXT Trials

Abstract Background: Regardless of adjuvant chemotherapy, the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy tamoxifen or exemestane in pre-menopausal women with estrogen receptor (ER)-positive breast cancer cause adverse events may affect adherence. Among the 22 targeted adverse events systematically reported in SOFT and TEXT trials, adverse events commonly experienced in exemestane–OFS group (32.3%) and tamoxifen–OFS group (31.0%), compared with tamoxifen alone group (24.6%). Side effects associated with endocrine therapy cause negative impact on adherence. Early discontinuation of endocrine therapy in 22.5%, 19.3%, and 23.7% of the tamoxifen, tamoxifen–OFS, and exemestane–OFS groups, respectively, in SOFT and TEXT trials. This report is intended to evaluate the possible contribution of the 8 most frequently studied side effects that have negative impact on adherence to hormone therapy in breast cancer. Methods: Calculating the probability of negative impact of most frequent endocrine therapy`s side effects (per SOFT-TEXT trials) on adherence per Leanne Fleming et al quantitative systematic review “The impact of medication side effects on adherence and persistence to hormone therapy in breast cancer survivors” Results: Musculoskeletal/joint pain had the most negative impact on the adherence in tamoxifen, tamoxifen–OFS, and exemestane–OFS groups (56%, 63% and 73%, respectively). Average of negative impact of tamoxifen, tamoxifen–OFS, and exemestane–OFS on adherence is 22%, 25% and 27%) Conclusions: The probability of adherence of using tamoxifen alone seems better than tamoxifen–OFS and exemestane–OFS. Citation Format: Tariq Hassan AL Qurayshah. Probability of negative impact on adherence caused by the most frequent side effects of adjuvant endocrine therapy for premenopausal breast cancer in SOFT and TEXT Trials [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B07.

Are breast cancer patients with suboptimal adherence to cardiovascular treatment more likely to discontinue adjuvant endocrine therapy? Competing risk survival analysis in a nationwide cohort of postmenopausal women

BackgroundHigh rates of discontinuation undermine the effectiveness of adjuvant endocrine therapy (AET) among hormone-receptive breast cancer patients. Patient prognosis also relies on the successful management of cardiovascular risk, which affects a high proportion of postmenopausal women. As with AET, adherence with cardiovascular drugs is suboptimal. We examined whether patient adherence with cardiovascular drugs was associated with the rate of AET discontinuation in a French nationwide claims database linked with hospitalisation data.MethodsWe identified postmenopausal women starting AET between 01/01/2016 and 31/12/2020 and taking at least two drugs for the primary prevention of cardiovascular disease (antihypertensive drugs, lipid-lowering drugs and platelet aggregation inhibitors) before AET initiation. Adherence was assessed for each drug class by computing the proportion of days covered. Women were categorised as fully adherent, partially adherent or fully non-adherent with their cardiovascular drug regimen based on whether they adhered with all, part or none of their drugs. AET discontinuation was defined as a 90-day gap in AET availability. Time to AET discontinuation according to levels of cardiovascular drug adherence was estimated using cumulative incidence curves, accounting for the competing risks of death and cancer recurrence. Multivariate cause-specific Cox regressions and Fine-and-Gray regressions were used to assess the relative hazards of AET discontinuation.ResultsIn total, 32,075 women fit the inclusion criteria. Women who were fully adherent with their cardiovascular drugs had the lowest cumulative incidence of AET discontinuation at any point over the 5-year follow-up period. At 5 years, 40.2% of fully non-adherent women had discontinued AET compared with 33.5% of partially adherent women and 28.8% of fully adherent women. Both partial adherence and full non-adherence with cardiovascular drugs were predictors of AET discontinuation in the two models (cause-specific hazard ratios 1.16 [95% CI 1.10–1.22] and 1.49 [95% CI 1.39–1.58]; subdistribution hazard ratios 1.15 [95% CI 1.10–1.21] and 1.47 [95% CI 1.38–1.57]).ConclusionClinicians should be aware that patients who do not adhere with their entire cardiovascular drug regimen are also more likely to discontinue AET. This stresses the importance of integrated care, as suboptimal adherence with both treatment components poses a threat to achieving ideal patient outcomes.

Adherence behaviours in breast cancer patients at risk of cardiovascular disease

Abstract Background High rates of discontinuation undermine the effectiveness of adjuvant endocrine therapy (AET) among hormone-receptive breast cancer patients. Patient prognosis also relies on the management of cardiovascular (CV) risk, which affects a high proportion of postmenopausal women. As with AET, adherence with CV drugs is suboptimal. We examined whether patient adherence with CV drugs was associated with AET discontinuation in a French nationwide claims database linked with hospitalisation data. Methods Women aged over 50 starting AET between 01/01/2016 and 31/12/2020 and taking at least two antihypertensive and/or lipid-lowering drugs were followed for 5 years or until AET discontinuation, 31/12/2021, death or cancer recurrence. Women were categorised as fully adherent, partially adherent or fully non-adherent with their CV drug regimen in the year before starting AET. The primary outcome was AET discontinuation, defined as a 90-day gap in treatment availability. Cumulative incidence curves were used to estimate time to discontinuation according to CV drug adherence and accounting for competing risks of death and cancer recurrence. Multivariate Cox and Fine-and-Gray regressions were used to assess the relative hazards of AET discontinuation while adjusting for potential confounders. Results 32,072 women fit the inclusion criteria. Fully adherent women had the lowest cumulative incidence of AET discontinuation at any point over the follow-up period. Partial adherence and full non-adherence with CV drugs were predictors of AET discontinuation in both models (cause-specific hazard ratios 1.15 [95% CI: 1.15-1.25] and 1.49[95% CI: 1.42-1.63]; subdistribution hazard ratios 1.15[95% CI: 1.09-1.21] and 1.47[95% CI: 1.38-1.57]). Conclusions Patients who do not adhere with their CV drug regimen are more likely to discontinue AET. Appropriate support should be brought to these patients as they may be at heightened risk of both cardiovascular and cancer-related events. Key messages • Concurrent management of cardiovascular health and breast cancer is essential and clinicians should know that patients with low adherence to cardiovascular drugs are more likely to discontinue AET. • Patients with suboptimal adherence across their drug regimen should be brought appropriate support as they may be at heightened risk of both cardiovascular and cancer-related events.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer

PurposeMammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain.MethodsWe evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided.ResultsAdjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33).ConclusionsThe prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

538 Background: Adjuvant endocrine therapy (ET) is the standard of care for Estrogen Receptor (ER)-positive early-stage breast cancer. However, many patients suffer from adverse events associated with ET. The prognosis of patients with T1a/bN0 breast cancer with ER-positive and human epidermal growth factor 2 (HER2)-negative is excellent, and it is not clear whether adjuvant ET should be recommended. Here we evaluate the effect of adjuvant ET for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Methods: This study was a multicenter, retrospective cohort study that evaluated adjuvant ET for patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Patients who underwent surgery between 2008 and 2012 in 47 institutions of the Japan Clinical Oncology Group (JCOG) breast cancer group were eligible. We analyzed the cumulative incidence of distant metastasis as primary endpoint using the Gray test model and time to event endpoints (distant disease free survival and overall survival) using log-rank test between patients treated with and without adjuvant ET. We also used Gray test model for the analysis of the cumulative incidence of ipsilateral and contralateral breast cancer. Predictive factors were assessed using the Fine-Gray model and the Cox proportional hazards model. Results: The median follow-up period was 9.2 years. Of 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%] diseases), 3991 (83.9%) received adjuvant ET. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In the multivariate analysis, the independent risk factors of distant metastasis were no ET, mastectomy, high grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% (HR, 0.54; 95% CI, 0.38-0.77). Adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs 6.9%; sHR, 0.17; 95% CI 0.11-0.28, and 1.9% vs 5.2%; sHR, 0.33; 95% CI, 0.22-0.49). Conclusions: Adjuvant endocrine therapy significantly reduces distant metastases, however the absolute difference is small for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, it reduced ipsilateral and contralateral breast cancer as well. Shared decision making regarding the omission of adjuvant endocrine therapy is crucial, especially in patients with low risk of distant metastasis.

Facing points of view: Representations on adjuvant endocrine therapy of premenopausal patients after breast cancer and their healthcare providers in France. The FOR-AD study.

Adjuvant endocrine therapy (ET) for 5-10 years is the backbone of the therapeutic strategy in patients with hormone receptor positive (HR+) early breast cancer (BC). However, long-term adherence to adjuvant ET represents a major challenge for most patients. According to prior studies, side effects of adjuvant ET are an important reason for poor adherence. In contrast, better communication and relational bond between patients and healthcare providers (HCPs) may improve adherence. The FOR-AD (Focus on non-adherence) study aimed at better understanding the representation of adjuvant ET by patients and their HCPs, in order to improve the care process. Three focus groups of premenopausal women (receiving adjuvant ET for variable amount of time) and two focus groups of HCPs (including oncologists, pharmacists, and nurses) were conducted, each including around ten participants. Thematic analyses using a general inductive approach were constructed to report participants' representations. Two main themes emerged across groups, and appeared of major importance. Representations on adjuvant ET were often homogenous within each group, but differed between patients and their HCPs. The relationship between both groups was considerably discussed, particularly its importance in facilitating adherence to adjuvant ET. Suggestions on improving the care process were also given, such as systematically including psychologists in follow-up care paths and having a nurse navigator follow patients under treatment with adjuvant ET. The present qualitative exploration may help buildi future tailored interventions to improve adherence to adjuvant ET, in particular regarding the role of nurse navigators.

Historical early treatment effects of adjuvant endocrine therapy for breast cancer in high-risk subgroups: Reanalysis of BIG 1-98, SOFT and TEXT.

508 Background: Clinical trials testing adjuvant endocrine therapy (ET) have not historically limited enrollment to patients with clinically high-risk breast cancer (BC), nor estimated treatment (trt) effects prior to 5 yrs. In light of recent trial results for adjuvant CDK4/6 inhibitors, we estimated early relative and absolute trt effects of aromatase inhibitor (AI) vs tamoxifen (T), with ovarian suppression (OFS) if premenopausal, in high risk subgroups. Methods: From pts enrolled in adjuvant phase 3 randomized clinical trials BIG 1-98 (postmenopausal, 5yr AI v T), TEXT (5yr AI+OFS v T+OFS) and SOFT (5yr AI+OFS v T+OFS v T), we identified subgroups with HR+/HER2- BC and high risk features (≥4 pLN; or 1-3 pLN with grade 3, pT≥5 cm and/or Ki-67≥20% [retrospectively centrally assessed]). TEXT randomized at start of adjuvant trt; BIG 1-98 and SOFT after chemotherapy. Disease-free survival (DFS) was defined from randomization to invasive recurrence at local, regional, distant or contralateral breast, second non-breast malignancy or death. We estimated trt effects as differences in 2, 3 and 5yr DFS Kaplan-Meier estimates (KM diffs at t yrs) and hazard ratios over time intervals of 0-2, 0-3 and 0-5 yrs (HRs over 0 to t yrs) to approximate the maturity of trial results with increasing follow-up. Results: The high-risk HR+/HER2- subgroups were 695/4922, 707/2660 and 526/3047 pts in BIG 1-98, TEXT and SOFT with 202, 122, 142 DFS events observed by 5 yrs since randomization. 60%, 46% and 44% of pts had ≥4 pLNs; 42%, 90% and 92% had chemotherapy. The table summarizes results. Conclusions: In re-analysis of clinical high risk HR+/HER2- subgroups of 3 trials each ̃700 pts, 5 yrs AI vs T had similar magnitude of early trt effects after 2-3 yrs follow-up of all pts vs trt effects observed after 27 mos median follow-up in monarchE trial (HR=0.70; KM diffs 2.7% at 2 yrs, 5.4% at 3 yrs; n=5637). Relative and absolute trt effects sometimes diminished when estimated over 5 yrs rather than over 2 yrs, but meaningful absolute differences remained at 5 yrs in contrast to Penelope-B trial results. Design and interpretation of high risk HR+/HER2- early BC trials may depend on timing of randomization and selection of backbone adjuvant trts; follow-up >5 yrs must remain standard. [Table: see text]

Abstract P4-11-27: A multimodal and personalized digital companion to help survivors of breast cancer (BC) manage side effects of adjuvant endocrine therapy (ET): A qualitative exploration

Abstract Background: Mobile health (mHealth) applications (app) and remote monitoring demonstrated tangible value in terms of improving dose delivery, quality of life and mitigating the severity of acute treatment-related side effects, both in the metastatic setting and during the active phase of treatment in patients (pts) with early-stage solid tumors. However, the value of mHealth in ‘after primary treatment’ survivorship phase is less studied. Most BC pts have hormone receptor-positive disease and are eligible for adjuvant ET for 5-10 years. ET is associated with multiple side effects that negatively impact quality of life and treatment adherence. A prior survey among French survivors suggested that pts are willing to use digital companion app to help them in the after-cancer experience. In this setting, we developed a digital companion for survivors of BC receiving ET. Objectives: In this study, we explored acceptability, representations, levers, and barriers to a multimodal mHealth intervention among BC pts treated with ET. Methods: This was a qualitative study based on 3 focus groups (FG) with survivors of BC receiving adjuvant ET. The multimodal mHealth intervention had the following features: measure (symptom reporting), understand, and appease (information on interventions to relieve the symptom). FG were conducted via videoconference, lasted approximately 60-90 min, were recorded and transcribed for analysis. A content, thematic analysis was performed. All participants provided oral informed consent and socio-demographic information. Results: 17 BC survivors from diverse professional and socio-economic background participated. Mean age was 48.5 years (range: 32-61). There was a consensus regarding the acceptability and perception of usefulness of an app during treatment with adjuvant ET. A feeling of loneliness during this period was also expressed. Emergent themes cited included: a) positive representations i) satisfaction with the educational support with language and the level of information of the app judged as appropriate and reliable; ii) hope in the role of the app as a companion to alleviate the loneliness; iii) vehicle to enhance family interaction; iv) tool to boost engagement towards their treatment. b) concerns associated with i) fear of human contact replacement ii) fear of loss of interest over time, particularly in the setting of a 5-10 year journey. Pts were pro-active in providing feedback regarding innovative features that could be integrated: i) including interest on the use of biosensors (step counting, nutritional tracking); ii) to receive personalized encouragement messages and iii) updated information regarding scientific advances related to the treatment of early breast cancer. Most participants found the app to be aesthetically pleasing and easy to use. Conclusions: Findings from this qualitative study are promising regarding the acceptability and perception of usefulness of a personalized app for the mitigation of ET side effects in the adjuvant setting. It highlights the need of personalized educational material, but also maintenance of ‘bi-directional’ communication with health professionals. Optimization of the tool is ongoing and updated FG results will be presented. This tool will be tested in a randomized controlled trial starting in Q1/2022, which will evaluate its effectiveness. Quotes from participantsThemes emergedParticipants’ quotes from focus groupsSatisfaction with educational support‘’Today we find everything on the internet, bad and good things, we cannot know what is true and what is fake. (⋯) If an app can give us reliable information, good, summarized information, this would be great!’’Satisfaction with educational support; Hope in the role of the app to alleviate loneliness“I didn’t even know we had so many side-effects linked to endocrine therapy. Now I understand that it’s true, it’s not something from my head. It’s related to the treatment and it’s really nice to have this support.”Alleviation of loneliness‘’I often feel lonely, sometimes is difficult to have contact with the doctor.’’, ‘’We feel lonely, even our family cannot understand.’’Alleviation of loneliness‘’We need to exchange with people that lived the same situation.’’, “We go to forums, chats, Instagram⋯”, ‘’We realize that we are not alone, that we are not the only ones with the symptoms.’’Fear of human contact replacement‘’It is a good addition, but it will never replace the relationship that we have with our doctor.’’Fear of loss of interest over time‘’It is a good app to start endocrine therapy⋯ How to make the app interesting and useful during several years of treatment?’’ Citation Format: Elise Martin, Antonio Di Meglio, Pietro Lapidari, Daniele Presti, Davide Soldato, Léna Degousee, Marion Aupomerol, Barbara Pistilli, Léonor Fasse, Diane Boinon, Florian Scotte, Gwenn Menvielle, Agnès Dumas, Céline Lazorthes, Jonathan Benhamou, Matthieu Pozza, Raphaëlle Martin-Neuville, Nicolas Helleringer, Jeanne Eelkema, Fabrice Andre, Ines Vaz-Luis, Maria Alice Franzoi. A multimodal and personalized digital companion to help survivors of breast cancer (BC) manage side effects of adjuvant endocrine therapy (ET): A qualitative exploration [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-27.

Abstract OT2-02-01: Utilization of patient reported outcomes generated by electronic medical record and smart pill bottles with follow up telehealth encounters to improve adherence to adjuvant endocrine therapy in breast cancer patients

Abstract Background: The use of adjuvant endocrine therapy (ET) in the form of tamoxifen (TAM) or an aromatase inhibitor (AI) for up to 10 years is the standard of care (SOC) for women with hormone receptor positive (HR+) breast cancer (BC). These agents can reduce recurrence by 30-50% and reduce mortality by approximately 1/3 irrespective of the use of chemotherapy (CT). Many women have difficulty with long-term compliance and persistence due to side effects and may ultimately self-discontinue. In the EBCTCG meta-analysis, evaluating 20 separate trials of adjuvant TAM for 5 years versus no adjuvant TAM, there was an estimated 80% adherence. Other BC trials have demonstrated lower adherence to TAM, dropping to 50% by years 4-5. Additionally, within the first year, discontinuation rates have been reported to be as high as 20-23%. In this investigator-initiated clinical trial we aim to evaluate the utility of one of two interventions a) serial electronic medical record (EPIC) generated patient (pt) reported outcomes (PRO)and pt surveys, OR b) a smart pill bottle, in increasing adherence to adjuvant ET over a 12-month interval during the first 4 years of adjuvant ET. The study also includes research-specific Telehealth (TH) visits when indicated in response to reports of increased toxicity or non-compliance. Methods: This is the Phase II, randomized, open-label, three-arm, multi-site study that will randomize 285 pts ≥18 years of age with stage 0-III HR+ BC in a 1:1:1 fashion with 95 patients in each arm. Arm A includes standard of care (SOC) quarterly visits (in-person or TH) with the treating provider during 12 months follow-up. Arm B is SOC quarterly visits during 12 months follow up, 18 electronic surveys every 3 weeks in between the SOC visits. Arm C is SOC quarterly visits during for 12 months follow up and use of electronic smart pill bottle with daily reminders to take ET. Primary Objective is to evaluate if the intervention of utilization of automated PROs and follow up TH encounters or the utilization of Smart Pill Bottles and follow up TH encounters can improve patient adherence with adjuvant ET within 12 months of study participation during the first 4 years of ET. The secondary objective is to evaluate if these interventions can improve quality of life and decrease side effects of adjuvant ET. The trial is open with 119 patients enrolled at the time of this abstract submission. ClinicalTrials.gov Identifier: NCT04054557 Citation Format: Utilization of patient reported outcomes generated by electronic medical record and smart pill bottles with follow up telehealth encounters to improve adherence to adjuvant endocrine therapy in breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-02-01.

Abstract PO-097: Treatment-related toxicities in Black and White women taking adjuvant endocrine therapy

Abstract Purpose: The effectiveness of adjuvant endocrine therapy (AET) to reduce morbidity and mortality among women diagnosed with hormone-receptor positive (HR+) breast cancer (BC) is well understood, yet the potential debilitating toxicities for Black survivors is not. Further, symptom toxicities impact treatment adherence. Using a mixed methods approach, this study examined patterns of reported AET- related toxicities in HR+ Black and White survivors. Methods: Study participants were enrolled in the Women’s Hormonal Initiation and Persistence study, a longitudinal observational trial of women diagnosed with HR+ breast cancer. Data regarding patient (e.g. race), medication (e.g. AET type), cancer care delivery (e.g. communication), and clinicopathologic factors (e.g., chemotherapy) were collected via surveys and medical charts. The FACT-ES assessed AET toxicity at baseline, 12 and 24 months. Primary analyses focused on the first year; secondary analyses explored changes over time. Multivariable linear regression models examined predictors of AET overall toxicity and for 5 toxicity subgroups. Focus groups with women (N=30) prescribed AET were transcribed verbatim, coded and analyzed. Results: Of the 570 participants, 28% were Black. Black women were more likely to have chemotherapy prior to starting AET but as likely as whites to have radiation. Most women (62%) were taking aromatase inhibitors (AIs). In unadjusted analyses Black women reported more overall, vasomotor, neurological, and gastrointestinal toxicities (p<.05). Race was insignificant in multivariable analysis. Factors associated with higher AET toxicity were higher medication concerns (ß=1.29; CI: 0.88 – 1.69; p<0.001), younger age (ß=-0.23; CI: -0.36 – -0.10; p<0.001), and lower satisfaction with care (ß=-0.24; CI: -0.48 – 0.01; p=0.041). Higher AET gynecological toxicities were associated with AI use (vs. Tamoxifen) (p=0.002) Trends of toxicities over time suggest higher overall reporting by Black women (P=0.07). Qualitative analysis revealed that most women were not prepared for AET toxicities and desired more information at the start of AET. More often than Whites, Black women reported receipt of less information from providers and emphasized that spiritual coping supported their ability to adhere to AET therapy despite toxicities. Conclusion: During the first year of AET, racial disparities in toxicity diminished when controlling for psychosocial and communication factors. Development of interventions that target these factors may enhance symptom management, self-care, and potentially adherence. Citation Format: Vanessa B. Sheppard, Arnethea L. Sutton, Reuben Retnam, Kandace P. McGuire. Treatment-related toxicities in Black and White women taking adjuvant endocrine therapy [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-097.

Using time series analysis to forecast the health-related quality of life of post-menopausal women with non-metastatic ER+ breast cancer: A tutorial and case study.

Time series models are widely used forecasting techniques in health care for long time series and are typically built in commercial statistical packages. However, for short time series data, such as health-related quality of life (HRQoL), guidance on how to select and use appropriate time series models is lacking. This tutorial provides a step-by-step guide adopting a time series analysis framework for HRQoL forecasting. We walk through a case study examining the forecasting of the effects of adjuvant endocrine therapy on the HRQoL of post-menopausal women with non-metastatic ER+breast cancer using data from the HRQoL sub-protocol of the Tamoxifen arm of the Arimidex, tamoxifen, alone or in combination (ATAC) trial. The forecasting of HRQoL consists of four steps: 1) data extraction and accuracy check, 2) forecasting horizon definition and identification of data pattern, 3) forecasting model identification and fitting using five forecasting approaches appropriate for short time series ((i) double exponential smoothing, (ii) double moving average, (iii) fuzzy forecasting, (iv) grey forecasting, and (v) Volterra series), 4) forecasting model selection. A user-friendly visual basic for applications (VBA) Excel add-in is made available to interested users to facilitate the application of the tutorial. The Grey method and Volterra series appeared to be good candidates to forecast the effects of adjuvant endocrine therapy on the HRQoL of post-menopausal women with non-metastatic ER+breast cancer enrolled in the ATAC trial. It is feasible to forecast the effects of treatments on HRQOL even when the time series is short.

The effects of adjuvant endocrine therapy on bone health in women with breast cancer.

In women with oestrogen receptor (ER)-positive early breast cancer, oestradiol is important for breast cancer development and progression. Endocrine therapy prevents the deleterious effects of oestradiol in breast tissue by systemically depleting oestradiol concentration (aromatase inhibitors) or preventing its local action in breast tissue (selective oestrogen receptor modulators i.e. tamoxifen), thereby improving oncological outcomes. Use of aromatase inhibitors in postmenopausal women and ovarian function suppression with either tamoxifen or aromatase inhibition in premenopausal women, consequent to systemic oestradiol depletion, exerts detrimental effects on skeletal health. The oestradiol-deficient state causes increased bone remodelling and a negative bone balance. This results in bone loss, microstructural deterioration and bone fragility predisposing to fractures. Similar effects are also seen with tamoxifen in premenopausal women. In contrast, use of tamoxifen in postmenopausal women appears to exert protective effects on bone but studies on fracture risk are inconclusive. The longevity of women with ER-positive breast cancer treated with adjuvant endocrine therapy emphasises the need to mitigate the adverse skeletal effects of these therapies in order to maximise benefit. In general, fractures are associated with increased morbidity, mortality and are a high socioeconomic burden. Whilst the efficacy of antiresorptive therapy in preventing bone mineral density loss in postmenopausal women has been established, further clinical trial evidence is required to provide guidance regarding fracture risk reduction, when to initiate and stop treatment, choice of agent and optimal management of bone health in premenopausal women receiving endocrine therapy. In addition, potential oncological benefits of antiresorptive therapies will also need to be considered.

Cognitive effects of adjuvant endocrine therapy in older women treated for early-stage breast cancer: a 1-year longitudinal study.

Evidence suggests endocrine therapy (ET) for breast cancer (BC) has adverse cognitive effects, but its specific effects on older women are unknown. This is despite the fact that older women are at increased risk of both breast cancer (BC) and cognitive decline relative to younger women. This study prospectively examined the cognitive effects of ET in a cohort of older BC patients. Our primary outcome measure was change in verbal memory, the cognitive domain most consistently affected by estrogen deprivation. Forty-two chemotherapy-naïve women age 60+, without dementia and recently diagnosed with hormone receptor-positive BC, completed neuropsychological tests at the time of ET initiation and after 1year of treatment. Change in age-standardized verbal memory performance was examined using paired t tests. To assess a broader range of potential cognitive effects, we also examined changes in visual memory, processing speed, frontal executive function, and perceptual reasoning. Participants exhibited significant decline from baseline to 1year in verbal memory (p =0.01). This decline was small to moderate in effect size (d = - 0.40). Performance on other domains did not change significantly over the year (all p > 0.05). Our findings suggest potentially detrimental effects of ET on verbal memory in older women after just 1year of treatment. Given that ET is prescribed for courses of 5 to 10years, additional studies examining longer-term effects of treatment in older women are critical.

Adverse effects of adjuvant endocrine therapy

Hormonal therapy is a highly effective and well tolerable treatment of hormone-responsive breast cancer. However, it has some side effects that can affect quality of life and lead to treatment discontinuation. Common side effects of tamoxifen and aromatase inhibitors are discussed in this article: menopausal, gynecological symptoms, cardiovascular and musculoskeletal adverse events. Some of them are preventable and manageable. In order to maintain good quality of life during treatment the oncologists should pay more attention to the side effects that lead to it’s deterioration and not be too anxious about insignificant ones.

Longitudinal Effects of Adjuvant Endocrine Therapy on the Quality of Life of Post-menopausal Women with Non-metastatic ER+ Breast Cancer: A Systematic Review.

BackgroundAnti-estrogen (ER) endocrine therapy is an effective treatment strategy in reducing breast cancer mortality. This therapy has a better therapeutic index than chemotherapy but can still affect patients’ quality of life (QOL) over time.ObjectiveThe objectives of this systematic review were to (1) describe QOL instruments used in ER-positive (ER+) non-metastatic breast cancer trials and (2) document the longitudinal effects of adjuvant endocrine therapy on the QOL of post-menopausal women with ER+ non-metastatic breast cancer.MethodsWe searched three electronic bibliographic databases for articles published from inception to October 2017 that described (1) a randomized controlled trial (RCT) of non-metastatic breast cancer containing an adjuvant endocrine regimen in at least one arm; (2) the use of a patient self-report measure assessing general or breast cancer-specific QOL; and (3) QOL outcomes at multiple time points during follow-up of at least 5 years. All included trials were independently evaluated by two reviewers, and data were extracted using standardized forms.ResultsIn total, 13 studies met our inclusion criteria and were assessed in this review. The quality of the trials was reasonably good. The top three most commonly used QOL instruments in the trials were the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy, the Short Form-36 and the Menopause-Specific Quality of Life. Most studies found no differences between tamoxifen and aromatase inhibitor groups in terms of global QOL. QOL data affected treatment regimen recommendations in a few cases. A meta-analysis was not feasible because the RCTs included in our review varied in terms of sample size, comparators, QOL instrument used, and timing of QOL measurement. Additionally, as no search strategy has perfect sensitivity, specificity and accuracy, there is always a chance that potentially relevant articles were missed.ConclusionThis systematic review suggests that the QOL of post-menopausal women is unlikely to be adversely affected by long-term use of adjuvant endocrine therapy. Efforts are needed to improve the quality of QOL reporting in clinical trials.Electronic supplementary materialThe online version of this article (10.1007/s41669-018-0070-7) contains supplementary material, which is available to authorized users.

Exploring knowledge, attitudes and experience of genitourinary symptoms in women with early breast cancer on adjuvant endocrine therapy.

Clinical trials of adjuvant endocrine therapy in women with early breast cancer have consistently reported that genitourinary symptoms are common. However, little is known about women's experiences of genitourinary symptoms, their views about the symptoms and how they impact on their lives. The aim of this study was to explore knowledge, attitudes and experiences of genitourinary symptoms among women receiving adjuvant endocrine therapy for early breast cancer. Thirty-two semi-structured interviews were conducted and subjected to a rigorous qualitative analysis. Genitourinary symptoms were commonly reported to negatively impact on personal, social and physical activities, were often attributed to anxiety and stress and were a source of embarrassment. Women also commented on the limited information available or provided regarding the potential genitourinary adverse effects of adjuvant endocrine therapy. There was a general lack of awareness that their symptoms could be associated with or exacerbated by adjuvant endocrine therapy. Women indicated a preference to receive information and advice about potential management options from either their general practitioner or specialist. These findings underscore the importance of improving communication and increasing awareness among both clinicians and patients about the potential impact of adjuvant endocrine therapy on genitourinary symptoms.

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy.

There is increasing attention and concern about managing the adverse effects of adjuvant endocrine therapy for women with early breast cancer as the side effects of therapy influence compliance and can impair quality of life (QoL). Most side effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are directly related to estrogen deprivation, and the symptoms are similar to those experienced during natural menopause but appear to be more severe than that seen in the general population. Prolonged estrogen deprivation may lead to atrophy of the vulva, vagina, lower urinary tract and supporting pelvic structures, resulting in a range of genitourinary symptoms that can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of QoL. The genitourinary side effects may be prevented, reduced and managed in most cases but this requires early recognition and appropriate treatment. We provide an overview of practical clinical approaches to understanding the pathophysiology and the management of genitourinary symptoms in postmenopausal women receiving adjuvant endocrine therapy for breast cancer.

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial

Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493.

The impact of adjuvant endocrine therapy in early breast cancer on quality-of-life: an overview of prospective trials

ABSTRACTAlthough endocrine therapy (ET) plays a crucial role in the adjuvant treatment of ER-positive breast cancer, a significant proportion of patients discontinue treatment early because of toxicity. In recent years a number of papers have attempted to quantify the impact of adjuvant ET on the quality-of-life (QOL) of the patient. The aim of this present review is to report the results of prospective trials that have measured the effect of adjuvant ET on the QOL in breast cancer patients. In most trials a great discrepancy has emerged between the magnitude of treatment-related symptoms and a drop in different QOL domains. In fact, the average change of QOL scores, if present, was unexpectedly small. Moreover, aromatase inhibitors were shown to have an unfavorable profile when compared to tamoxifen, in the up-front or switched schedule, or to placebo, in the extended strategy. Further studies are warranted to implement more sensitive and largely accepted QOL instruments.

Cognitive effects of endocrine therapy for breast cancer: keep calm and carry on?

The number of breast cancer survivors is gradually increasing and a subset of these patients experience long-term adverse effects of adjuvant systemic therapy, including cognitive decline. Surprisingly, relatively little is known about the long-term adverse effects of endocrine treatment on cognition. As 75% of all patients with breast cancer are eligible to receive hormonal treatment, understanding the potential neurocognitive adverse effects of such therapy is of utmost importance. Concerns about adverse cognitive effects of adjuvant endocrine therapy are timely, as recently updated guidelines recommend increasing the length of such therapy from 5 years to 10 years for a subset of patients. The decline of cognitive functions can have a detrimental impact on quality of life and might interfere with independent living. This Review discusses the tissue-selective side effects of endocrine therapies and specifically their impact on cognitive function, on the basis of clinical data; the neurobiological effects of endocrine therapies as observed in preclinical models are also discussed. We highlight the critical issues that need to be addressed in future preclinical and clinical studies in order to best assess the cognitive effects of endocrine treatment in patients with breast cancer.