Side Effects Of Hormone Therapy Research Articles

Adherence to endocrine therapy with tamoxifen and satisfaction with follow-up of women with breast cancer by a gynecologist: A survey study

Background. Side effects of endocrine therapy with tamoxifen (TAM) reduce the quality of life of patients with breast cancer (BC) and adversely affect treatment compliance. Against the background of treatment of BC with TAM, the risk of developing endometrial hyperplasia (EH) increases. At the moment, algorithms for monitoring patients receiving TAM by an obstetrician-gynecologist have not been developed and approved. There are also divergent opinions of experts regarding the diagnosis and management of patients in the detection of EH. This article presents the results of the final stage of the study in 2017–2022 – a survey study. The purpose of this study was to assess adherence to endocrine therapy and satisfaction with observation by a gynecologist of women with BC after 5 years of observation and their relationship with the identified early associated polymorphisms of the CYP2D6, CYP3A5, CYP2C9 and ABCB1 genes. Materials and methods. 54 patients with BC, out of 120 who had previously passed the first pharmacogenetic stage of the study, were interviewed with specially designed questionnaire. Due to the small sample size, delta percentages (∆%) were used in each comparison group with a difference threshold of 5%. To assess associations with the studied genetic polymorphisms, previously obtained significant associations of adverse drug reactions with pharmacogenetics in the same patients were used. Results. The prevalence of all adverse drug reactions (ADRs), with the exception of EH, was higher in the group of patients who canceled TAM. Over 5 years of follow-up, 57.4% of patients were regularly observed by an obstetrician-gynecologist, 42.59% of patients visited a gynecologist less than once a year. Of all the respondents, 53.7% of patients are satisfied with the regularity and quality of dispensary observation by an oncologist, 33.33% of patients are satisfied with the regularity and quality of dispensary observation by an obstetrician-gynecologist. All studied ADRs (EH, hot flashes, asthenia, bone pain and dyspepsia) associated with various genetic polymorphisms, prevailed in the group of patients who stopped taking TAM due to drug intolerance (∆%: 25.72, 6.97, 4.81, 6.97 and 24.52 respectively) compared with the TAM-group. Conclusion. The results obtained confirm the role of the studied genetic polymorphisms in the development of ADRs of TAM, but only systemic (hot flashes, asthenia, bone pain and dyspepsia). With regard to endometrial hyperplasia, no significant differences were obtained, which requires more extensive studies.

Abstract PO5-12-05: A Retrospective Study of the Rate of Cognitive Impairment and Influencing Factors during Postoperative Endocrine Therapy for Breast Cancer

Abstract Background Although cancer-related cognitive impairment (CRCI) has been gradually recognized, general cognitive function tests such as the MMSE are not sensitive enough to diagnose CRCI. There is also a lack of evidence on the incidence and its response. However, even mild cognitive impairment can have a significant impact on quality of life. In this study, we retrospectively analyzed the prevalence of cognitive impairment in patients undergoing endocrine therapy at our hospital and the factors influencing the symptoms. Subjects 349 patients who continued single-agent postoperative endocrine therapy for at least 6 months between January 1 and October 31, 2022, and who responded to the cognitive dysfunction questionnaire at least once. Data from the cognitive dysfunction items of the endocrine therapy questionnaire administered during the period were used to retrospectively examine the CRCI awareness rate and factors involved. Results and Discussion The patients who were aware of cognitive dysfunction was 170, or 49% of all patients, and univariate analysis showed that age was significantly higher in the group with CRCI, but there were no significant differences in type of endocrine therapy or history of chemotherapy between the groups with and without CRCI. Physical symptoms such as menopausal symptoms (hot flashes and sweats), arthralgia, myalgia, fatigue, depressed mood, and malaise were significantly more frequent in patients with CRCI, which could be considered side effects of endocrine therapy. Risk factors such as low cognitive reserve, low level of education, advanced age, race, depression, fatigue, and anxiety have been reported in the past, and in this study, fatigue, depressed mood, and malaise were found significantly more frequently in patients with cognitive dysfunction. However, the diagnosis of depression and dementia may also be important.Non-pharmacological interventions, especially cognitive rehabilitation and exercise, are expected to be effective in improving symptoms, but there is no certain opinion yet. The limitation of this study is that it was a single-center, retrospective analysis. In addition, it was difficult to evaluate the results over time, including before the start of oral medication, so we are considering conducting a prospective data collection study so that comparisons can be made in the future. Conclusion: This study was a simple screening, based only on subjective symptoms. In recent years, postoperative endocrine therapy has been prolonged to 10 years, and there is a possibility to improve the quality of life of patients by recognizing the possibility of cognitive dysfunction in both providers and patients, and by taking measures that include multiple factors. Citation Format: Akari Murakami, Mayuko Aono, Kaho Utsunomiya, Kumiko Okujima, Kana Takemoto, Megumi Takaoka, Erina Kusakabe, Kana Taguchi, Kanako Nishiyama, Yoshiaki Kamei, Yasutsugu Takada, Hitoshi Tanimukai. A Retrospective Study of the Rate of Cognitive Impairment and Influencing Factors during Postoperative Endocrine Therapy for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-05.

Barriers to endocrine therapy adherence: perspectives of Black breast cancer survivors and their providers.

Adherence to oral endocrine therapy (ET) remains an issue for up to half of women prescribed these medications. There is emerging data that Black breast cancer survivors (BCS) have lower rates of ET adherence. Given the disparities in breast cancer recurrence and survival for Black BCS compared to their White counterparts, the goal of this study is to better understand barriers to ET adherence among Black BCS from the patient and provider perspectives. In this qualitative study, we conducted semi-structured interviews between October 29, 2021, and March 1, 2023. Interviews were recorded and transcribed, and coded data were organized into primary and secondary themes. Participants were recruited from a single academic cancer center. A convenience sample of 24 Black BCS and 9 medical oncology providers was included. Eligible BCS were 18years or older, English-speaking, diagnosed with stage I-III hormone receptor-positive breast cancer, who had initiated ET. Mean age of the BCS was 55years (interquartile range, IQR 17years). About one-fourth had a high school diploma or less (26.1%) and 47% completed a college education or higher. Approximately one-third of participants had annual household incomes of $40,000 or less (30.4%) or more than $100,000 (30.4%). Forty-three percent of the patient participants had private insurance; 11% were insured through Medicaid or the federal healthcare exchange; 26.1% had Medicare; and 13% were uninsured. Of the 9 medical oncology providers interviewed, 2 were advanced practice providers, and 7 were medical oncologists. We found 3 major themes: (1) Black BCS often had concerns about ET before initiation; (2) after initiation, both BCS and providers reported side effects as the most impactful barrier to ET adherence; and (3) survivors experienced challenges with managing ET side effects. Our results suggest that multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black women and may reduce disparities in outcomes. Multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black breast cancer survivors.

Therapeutic efficacy and anti-inflammatory mechanism of baicalein on endometriosis progression in patient-derived cell line and mouse model

BackgroundBaicalein is a flavonoid extracted from the roots of Scutellaria baicalensis G. that has anti-inflammatory and antitumor effects. However, therapeutic mechanisms of baicalein in patients with endometriosis in vivo have yet to be elucidated. As a chronic inflammatory gynecological disease, endometriosis causes pain and infertility, and has no complete treatment to date. Current treatment strategies cause several side effects and have high recurrence rates. PurposeThis study aimed to identify the in vivo therapeutic effects of baicalein on endometriosis and verify the action mechanisms of baicalein, focusing on regulating inflammation. MethodsIn this study, an autologous transplant mouse model and patient-derived immortalized human ovarian endometriotic stromal cells (ihOESCs) were used to investigate the therapeutic activities of baicalein. The mouse model was administered with 40 mg/kg baicalein by oral gavage for 4 weeks, and the treatment outcomes of baicalein-treated mice were compared with vehicle- and dienogest-treated groups. ihOESCs were treated with 0-5 μg/ml baicalein for in vitro studies. ResultsBaicalein significantly alleviated the progression of endometriosis in mouse models. Baicalein reduced the expression of proinflammatory cytokines in endometriotic lesions and ihOESCs, and cytokine expression and T cell proportions in mouse spleen. in vitro results showed that baicalein increased mitochondrial calcium flux and induced mitochondrial depolarization and ROS generation in ihOESCs. Ultimately, baicalein inactivated the MAPK/PI3K signaling and induced cell death in ihOESCs. ConclusionIn conclusion, baicalein effectively attenuated the progression of endometriosis through its anti-inflammatory activities. Baicalein can be an alternative or supplemental treatment for endometriosis to ameliorate the side effects of hormonal therapy.

Effect of Salvia officinalis scent on postmenopausal women’s sexual function and satisfaction: a randomized controlled trial

IntroductionSexual function is one of the important aspects of quality of life which is often impaired after menopause. Given the side effects of hormone therapy on postmenopausal women, alternative treatments such as aromatherapy have won popularity. The aim of this study was to investigate the effect of aromatherapy using Salvia officinalis on the sexual function and satisfaction of postmenopausal women.MethodsThis was a double-blind randomized controlled trial conducted on postmenopausal women referring to health centers in Kermanshah, Iran, in 2018. The participants were randomly divided into two groups: Salvia officinalis (n = 32) and control (n = 32). Women in the intervention group received 2 drops of Salvia officinalis essential oil by inhalation twice a day for 5 consecutive days of a week continued for 6 weeks. The control group received almond oil in the same dosage and frequency. Sexual function and satisfaction were evaluated using the Lindberg sexual satisfaction questionnaire and the female sexual function index, respectively before the intervention and 6 weeks after it.ResultsAfter 6 weeks of intervention, the total mean scores of sexual function (28.8 ± 2.13 vs.17.9 ± 1.59 P < 0.001) and sexual satisfaction (71.53 ± 5.86 vs. 50.44 ± 10.41) were significantly higher in the Salvia officinalis group compared with the control group, respectively.ConclusionThe findings showed that aromatherapy using Salvia officinalis has a significant effect on improving sexual function and satisfaction in postmenopausal women. Therefore, given the prevalence of sexual disorders in postmenopausal women, aromatherapy using Salvia officinalis is recommended to be used for improving these disorders.Clinical trial registrationIranian Registry of Clinical Trials; https://en.irct.ir/user/trial/50212/view (IRCT20160427027633N6), registered (12/08/2020).

Side effects and impacts of extended adjuvant endocrine therapy: A qualitative study among women with HR+/HER2- breast cancer.

e12509 Background: Extended (≥5-year) adjuvant endocrine therapy (ET) is generally the preferred treatment approach for patients with hormone receptor–positive (HR+) breast cancer at high risk of recurrence. However, due to side effect burden and other challenges, patient adherence to extended adjuvant ET is often suboptimal, presenting challenges for patients and healthcare providers alike. To further understand potential barriers to adherence, the objective of this study was to explore the side effects and impacts of extended adjuvant ET among women with HR+ breast cancer through in-depth qualitative interviews. Methods: Individual qualitative interviews were conducted with 20 US women with a self-reported clinical diagnosis of nonmetastatic HR+/HER2− breast cancer who had undergone ≥4 years of adjuvant ET and were currently taking ET or had concluded their regimen within the past 12 months. Using thematic analysis methods, interview transcripts and interviewers’ field notes were analyzed to identify important concepts and dominant trends. Results: Interview participants averaged 52.8 years in age and were diverse in race, education level, and employment status. The most commonly reported ET side effects among the 20 participants were hot flashes (n = 16), joint pain (n = 15), difficulty sleeping (n = 15), difficulty with weight management (n = 15), fatigue (n = 15), reduced interest in sex (n = 14), and feeling irritable (n = 14). Participants most frequently identified joint pain (n = 8), reduced interest in sex (n = 4), and discomfort with intercourse (n = 4) as the most bothersome ET side effects. Participants generally reported that the frequency and severity of side effects that they experienced remained constant throughout the extended adjuvant period; only 3 reported having switched ET regimens to manage side effects. Participants reported numerous impacts from ET side effects, including to cognitive and physical functioning (most common), social interactions, and work/productivity. Several participants spoke about the tradeoffs they make in enduring ET side effects and impacts to reduce risk of recurrence. For most participants, the primary benefit of extended adjuvant ET was the perceived reduction of risk of recurrence; some reported “peace of mind” from taking ET, knowing they were doing everything possible to reduce their risk of recurrence. Several participants expressed reluctance to stop taking ET despite the side effects because adherence to their medication made them feel less anxious or worried about recurrence. Conclusions: Patients receiving ET for HR+/HER2− breast cancer continue to experience significant side effects during extended adjuvant ET, and these side effects impact quality of life in many ways. Some patients are nonetheless motivated to continue with long-term ET to reduce risk of recurrence and/or because of the emotional benefit it affords.

LESS: Single-arm study to de-escalate adjuvant endocrine therapy duration in post-menopausal women with HR+ HER2- early-stage breast cancer at very low risk of metastasis.

TPS615 Background: Adjuvant Endocrine Therapy (ET) is the cornerstone treatment of localized hormone-receptor positive (HR+) breast cancer, with demonstrated benefits on overall survival (30-40% relative decrease in mortality) but also on the risk of local and contralateral relapse (43-50% relative decrease). While the relative benefit of 5 years of ET is identical for small tumors as compared to larger ones, the absolute benefit is much lower, and the risk-benefit ratio becomes questionable given the frequent and impactful side effects of ET which are associated with non-adherence. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients. However, shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients. The purpose of this study is to demonstrate that adjuvant ET limited to 2 years of aromatase inhibitor (AI) in postmenopausal women at very low risk of recurrence as determined with a MammaPrint and BluePrint Ultra Low Risk Luminal test result can ensure very high survival without metastatic relapse and allows a reduction of side effects and a better quality of life. Methods: LESS (NCT05297617) is a prospective, national, multicenter, single-arm, interventional, non-threshold crossing phase II study evaluating a therapeutic de-escalation that limits adjuvant ET to 2 years of AI. Approximately 696 post-menopausal patients with an invasive unilateral, HR+, HER2-negative, without indication of adjuvant chemoT and genomically-assessed MammaPrint/BluePrint UltraLow risk Luminal A breast cancer tumors, will be enrolled. LESS will include two sub cohorts: the majority of patients with Grade 2, pT1c-2, pN0/N1mic tumors, and up to 80 patients ≥65 years with Grade 1, pT1, pN0 and Ki67&lt;10% tumors. The primary endpoint is distant metastasis free survival (DMFS) defined as the time from date of registration to date of first event of distant recurrence, death, or second primary non-breast invasive cancer. Secondary endpoints include the assessment of quality of life parameters and psychological aspects related to this de-escalation. The null hypothesis (H0) that, in the study population after 2 years of adjuvant AI, DMFS at 5 years is lower or equal to 94.5% will be tested against the alternative - that it is above 94.5%. For an expected DMFS of 96.7% under the alternative hypothesis, a total of 37 DMFS events are required in order to provide approximately 85% power at a one-sided significance level of 0.05 to reject H0 using a logrank test. The 1st patient was included in October 2022, initiating the 2-year inclusion period and 10 years FU per patient. Clinical trial information: NCT05297617 .

In Silico Evaluation of the Binding Energies of Androgen Receptor Agonists in Wild-Type and Mutational Models.

Anabolic androgenic steroids (AAS) are substances with androgenic and anabolic characteristics. Among the many side effects of hormone therapy with AAS, the following stand out: heart problems, adrenal gland disorders, aggressive behavior, increased risk of prostate cancer, problems related to lack of libido and impotence. Such substances vary in the relationship between androgenic activity, and the activation of the androgen receptor (AR) is of fundamental importance for the singularity of the action of each AAS. In this sense, our study evaluates the aspects that comprise the interactions of testosterone agonists (TES), dihydrotestosterone (DHT) and tetrahydrogestrinone (THG) in complex with the AR. In addition, we also evaluated the impact of ligand-receptor affinity differences in a mutation model. We apply computational techniques based on density functional theory (DFT) and use, as methodology, Molecular Fractionation with Conjugate Caps (MFCC). The energetic specificities present in the interaction between the analyzed complexes attest that the highest affinity with the AR receptor is found for AR-THG, followed by AR-DHT, AR-TES and AR-T877A-DHT, respectively. Our results also show the differences and equivalences between the different agonists, in addition to evaluating the difference between the DHT ligand in complex with the wild-type and mutant receptor, presenting the main amino acid residues that involve the interaction with the ligands. The computational methodology used proves to be an operative and sophisticated choice to help in the search for pharmacological agents for various therapies that have androgen as a target.

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

BackgroundInnovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. ObjectiveTo present the voting results of the APCCC 2022. Design, setting, and participantsThe experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysisThe panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitationsThe voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. ConclusionsThese voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient summaryThe Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter summaryReport of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-home messageAt APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

PS-BPC11-5: INCIDENCE OF CLINICAL HYPERTENSION IN YOUNG TRANSGENDER PEOPLE AFTER A FIVE-YEAR FOLLOW-UP: ASSOCIATION WITH GENDER-AFFIRMING HORMONAL THERAPY

Introduction and Objective: There is a paucity of data on the long-term cardiovascular side effects of hormonal therapy in transgender people. The most overlooked issue is the cardiovascular risk associated with the use of androgen blockers. While some short-term data on blood pressure effects of gender-affirming hormonal therapy are available, the risk of hypertension development is unknown. We sought to assess this risk in our transgender patients. Design and Methods: Retrospective analysis of the clinical records of consecutive transgender patients who began hormonal therapy in our Outpatient Gender Identity Clinic with &lt; 30 years of age and have a follow-up of at least 5 years. Patients who had office sitting BP &gt; 140/90 mmHg at least twice, had an ABPM or systematic HBPM register with &gt; 135/85 mmHg or were taking antihypertensive medication were diagnosed with hypertension. Mediation analyses with weight increase as mediator were performed post-hoc to quantify its relative contribution to the increase in blood pressure. Patients who were already living with hypertension at the onset of hormonal therapy, withdrew from it or switched androgen blockers were excluded. All subjects gave informed consent. Results: 129 transgender women treated with estradiol and 153 transgender men treated with testosterone were included. Their onset and 5-year follow-up age, blood pressure and body weight are shown in the Table (women are stratified by type of androgen blocker) along with the incidence of hypertension. The increase in body weight was strongly correlated with the SBP increase (Spearman's r: 0.361, p &lt; 0.001). Mediation analyses showed that 31.2% - 42.3% (95% CI) of the SBP increase was mediated by body weight increase but the rest was body weight-independent. Conclusions: The annual incidence of hypertension in young transgender men (1.17%) seems comparable to that of the general population, but in young transgender women the choice of androgen blocker has a remarkable effect on the incidence of hypertension, with apparent protective effect of spironolactone but a striking risk increase with cyproterone acetate (close to 5% yearly). Taken together with the known risks of this drug (meningioma, depression, low libido, liver toxicity, thrombosis…), the use of cyproterone acetate for this indication should be reconsidered. Body weight increase is undoubtedly related to the increase of BP transgender people on gender-affirming hormone therapy but is probably not the main factor.

Cost-Effectiveness Analysis of Ultra-Short Whole Breast Radiation Therapy Alone vs. Endocrine Only or Combined Treatment for Low-Risk ER-Positive Early-Stage Breast Cancer in Women Age 70 and Older

<h3>Purpose/Objective(s)</h3> The optimal management of early-stage, low-risk, hormone-positive breast cancer in women age 70 and older remains controversial. Recent trials have shown whole-breast radiation courses of only 5 fractions have similar outcome as longer courses, reducing the cost and inconvenience of treatment. We therefore performed a cost-utility analysis to compare ultra-short whole breast irradiation (U-WBI) to endocrine therapy (ET) alone and to combined ET and U-WBI. <h3>Materials/Methods</h3> We simulated the cost-effectiveness and acute and late effects of different treatment approaches for women age 70 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were: U-WBI performed with a 3D technique over 5 fractions without a boost ("RT Alone"), adjuvant ET (anastrozole for 5 years) without RT ("AI Alone"), or the combination of the two. The FAST-Forward trial served as the basis for this analysis. The combination strategy was calibrated to match the trial results. The relative effectiveness of the RT Alone and AI Alone strategies were inferred from historical randomized trials. Costs were obtained from 2022 Medicare rates. Utilities and other costs were obtained from the literature. The primary endpoint was the cost-effectiveness of the 3 strategies over a 10-year horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/QALY deemed "cost-effective". Deterministic and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. <h3>Results</h3> The model was validated using 500,000 simulated patients, each treated with the 3 strategies. The model results agreed well with the pre-specified target outcomes. On average, RT Alone was the least expensive strategy ($15,200), with AI Alone slightly more expensive, ($16,761), and combination therapy the most costly ($20,416). The most effective strategy was the combination (9.497 QALY), with small differences between RT Alone (9.453) and AI Alone (9.420). Therefore, the AI Alone strategy was more costly and less effective than RT Alone (dominated), and the combination therapy was slightly more expensive than the usual definition of "cost-effective" (ICER $117,721 relative to RT Alone). Probabilistic sensitivity analysis demonstrated RT Alone to be cost-effective in 52% of trials, with combination in 35% and AI Alone in 13%. <h3>Conclusion</h3> U-WBI without ET represents a cost-effective strategy for low-risk women in the United States, with slightly higher QALY outcome compared to AI Alone. Combination therapy improves outcome very modestly. Hence, many patients may prefer RT Alone in order to avoid the possible side effects of ET. Discussion of these options must account for patients' weighing of these issues.

Side Effects of Endocrine Therapy Are Associated With Depression and Anxiety in Breast Cancer Patients Accepting Endocrine Therapy: A Cross-Sectional Study in China.

ObjectiveHormone positive breast cancer patients bear side effects of endocrine therapy and that may be related to depression and anxiety. We sought to find an association between mental health and side effects of endocrine therapy.MethodsA total of 398 patients participated. Sociodemographic, disease profile, and side effects questionnaires were administered. We screened for depressive and anxiety disorders by using the SDS (Self-Rating Depression Scale) and SAS (Self-Rating Anxiety Scale).ResultsThe prevalence of depression and anxiety in our study were 33.4% (133) and 13.3% (53), respectively. Depression was linked to education level (≤8 years, OR = 3.59, 95% CI: 2.22–5.78), night sweats (yes, OR = 1.90, 95% CI: 1.17–3.09), vaginal dryness (yes, OR = 2.22, 95% CI: 1.19–4.16), and fatigue (yes, OR = 1.94, 95% CI: 1.21–3.11); anxiety was associated with education level (≤8 years, OR = 3.13, 95% CI: 1.62–6.08), time to diagnosis (≤ 3 years, OR = 2.14, 95% CI: 1.13–4.07), osteopenia (yes, OR = 2.43, 95% CI: 1.26–4.70), loss of hair (yes, OR = 2.80, 95% CI: 1.10–7.15), and fatigue (yes, OR = 2.89, 95% CI: 1.54–5.43). A stratified analysis according to age (≤45 years and > 45 years) was performed as an exploratory. None of factor-age interactions was statistically significant.ConclusionSide effects of endocrine therapy were significantly associated with anxiety and depression. Side effects deserve greater emphasis and clinical interventions are needed to reduce anxiety and depression in breast cancer patients accepting ET.

Feasibility of home-based exercise training in men with metastatic castration-resistant prostate cancer.

Home-based training increases accessibility to exercise and mitigates the side effects of hormone therapy for prostate cancer (PC). However, it is unknown if men with more advanced disease are willing to partake in such interventions. To determine the feasibility of a home-based exercise intervention in men with metastatic castration-resistant prostate cancer (mCRPC). mCRPC patients on androgen receptor signaling inhibitors (ARSI) were prescribed a 12-week, home-based exercise intervention using resistance bands and walking. Feasibility was assessed using recruitment, retention, adherence, and outcome capture. Physiological changes and patient reported outcomes were assessed before and after the intervention. Of the 62 referrals, 47 were eligible with 22 men performing baseline testing (47% recruitment rate) and 16 completing the intervention (73% retention). Task completion was >86% for all physiological tests. Walking adherence was 80% and resistance training was 63%, the latter falling short of the study target (75%). Training increased thigh muscle cross-sectional area by 22%, time to exhaustion by 19% (both p < 0.05) and peak oxygen uptake by 6% (p = 0.057). Improvements in short physical performance battery scores and 400 m walk demonstrated moderate effect sizes that did not reach significance. Home-based exercise is feasible during ARSI treatment for mCRPC. Greater endurance capacity and localized hypertrophy appear as the primary improvements following training. These preliminary findings suggest home-based training may increase exercise accessibility, with important lessons that will inform subsequent trials investigating the efficacy of home-based exercise interventions during mCRPC.

Sleepless and Spent in Survivorship: Fatigue and Insomnia in Breast Cancer Survivors.

It is estimated that there are 3.8 million breast cancer survivors in the United States. Addressing survivors' post-treatment needs is critical to providing quality healthcare. A standardized questionnaire for breast cancer survivors was employed to assess the health status, challenges, and concerns of our breast cancer patients at their survivorship visits, which were conducted 4months after surgery. All patients were seen in the breast center at one community hospital over a 6-year period. Responses to a standardized questionnaire that was administered to 505 consecutive breast cancer patients at their survivorship visits 4months after surgery were evaluated. The most striking finding was that 35% reported symptoms of insomnia, 26% had persistent fatigue, and 19% experienced fatigue that interfered with their usual activities. There was a significant association between symptoms of insomnia and radiation treatment (P = .004), pain (P < .001), hormone therapy (P < .01), and side effects of hormone therapy (P < .0001). There was also a significant association between fatigue and pain (P < .001) as well as side effects from hormone treatment (P = .0036). Over a third (35%) of breast cancer patients suffer from insomnia, while over a quarter (26%) complain of fatigue at their survivorship assessments. Contributing factors include radiation treatment, pain, and hormonal therapy. Careful assessment and treatment of fatigue and symptoms of insomnia in breast cancer patients is needed to improve quality of life for survivors.

Abstract OT1-01-01: A randomized, pragmatic trial investigating the timing of radiotherapy and endocrine in patients with early stage breast cancer (REaCT-RETT trial)

Abstract The optimal timing of commencing adjuvant endocrine therapy (ET) relative to adjuvant radiotherapy (RT) (i.e. concurrent with or sequential to radiotherapy) remains unknown. A systematic review performed by our team was unable to answer this question due to a lack of high quality, randomized data on concurrent versus sequential ET and RT. Surveys of physicians confirmed this uncertainty and highlighted theoretical concerns for increased side effects with concurrent treatment. Respondents showed keen interest in obtaining real world, randomized data to guide clinical practice. REaCT-RETT is a pragmatic, randomized, non-inferiority trial comparing concurrent and sequential ET and RT in early breast cancer (EBC). The primary endpoint will assess the change in ET side effects at baseline and 3 months post radiation, using the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), with primary analysis based on an analysis of covariance (ANCOVA). With a sample size of 176 patients (88 per arm), an ANCOVA would have 80% power (α=0.05) to detect effect sizes as small as 0.25 regardless of the correlation with covariates. It is hypothesized that concurrent therapy will be non-inferior to sequential therapy in terms of ET side effects. Secondary endpoints will examine RT toxicity, ET compliance, quality of life, and cost-effectiveness. Patients with HR positive EBC planned to receive both adjuvant ET and RT were eligible. Patients who previously received ET for invasive breast cancer, or RT in the same breast, were excluded. The trial is conducted by The Ottawa Hospital’s (TOH) innovative Rethinking Clinical Trials (REaCT) program (https://react.ohri.ca/) which strives to improve access to patient-centered, pragmatic clinical trials by removing barriers for patients and researchers. Integral features of the program include broad eligibility criteria, a verbal consent model, and pragmatic data collection and assessment procedures. REaCT is the largest pragmatic cancer clinical trials program in Canada, with over 3,200 patients randomized in 18 clinical trials at 15 sites across Canada. REaCT-RETT accrued patients from September 2019 to January 2021. Data collection is ongoing, with final patient follow up expected April 2022. The timing of accrual provided a unique opportunity to adapt in response to restrictions due to the COVID-19 pandemic, which began to impact trial sites in March 2020. The target sample size was met with 262 patients randomized (1:1) across 3 sites in Ontario, 98% from TOH. A mean of 19 patients/month were accrued prior to the pandemic, compared to a mean of 13 patients/month after March 2020. Twenty-two patients were removed due to withdrawal of consent, ineligibility, or physician choice, and the pandemic was not a significant contributing factor. Since March 2020 there have been 772 patient follow ups, of which 47% (364/772) have been virtual. Only 10% (102/1028) of trial mandated appointments have been missed to date. Compliance with baseline and 3-month FACT-ES questionnaires for the primary endpoint in evaluable patients was 90% (215/240) and 83% (198/240), respectively. The pandemic posed several challenges to the REaCT-RETT study including a decline in patient accrual, poor accrual at peripheral sites due to delayed opening, and a rapid switch to virtual patient care. However, the nimble REaCT methodology enabled virtual patient consent and data collection during the pandemic, allowing the trial to continue successfully, with final data expected for presentation summer 2022. Finally, despite the challenges of COVID-19 we have seen that patients and physicians remain interested in research, and we are applying valuable lessons learned to forthcoming REaCT trials to strengthen their performance during and beyond the ongoing pandemic. Citation Format: Sharon F Mc Gee, Mark Clemons, Michelle Liu, Mashari Jemaan Alzahrani, Terry Ng, Arif Awan, Sandeep Sehdev, John Hilton, Jean Michel Caudrelier, Marie France Savard, Lesley Fallowfield, Vikaash Kumar, Orit Freedman, Dean Fergusson, Gregory Pond, Brian Hutton, Jean Marc Bourque. A randomized, pragmatic trial investigating the timing of radiotherapy and endocrine in patients with early stage breast cancer (REaCT-RETT trial) [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 OT1-01-01.

Abstract OT1-11-02: A pragmatic, randomised, multicentre trial evaluating the dose timing (morning vs evening) of endocrine therapy and its effects on tolerability and compliance (REaCT-CHRONO Study)

Abstract Background. Endocrine therapy (ET) is the mainstay treatment for hormonal receptor positive (HR+) breast cancer. ET non-compliance and non-persistence vary from 30 to 70% and are associated with reduced disease-free and overall survival. ET side effects are an important cause of non-adherence. In clinical practice, there are anecdotal reports that time of the day at which ET is taken may affect ET side effects and compliance. However, we are not aware of any high-quality studies supporting this practice. In other fields of medicine, there is evidence to suggest that the time of the day at which medication is taken can alter its effect and/or the adherence. This is known as chronotherapy. Methods. In this pragmatic, open-label, multicenter trial, eligible and consented patients with an early stage or locally advanced HR+ breast cancer will be randomized (1:1) to receive either: an ET morning dose (Arm A: within 1 hour of the patient wake up time) or an ET evening dose (Arm B: within 1 hour of patient bed time). The primary endpoint is endocrine toxicity and tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline to 12 weeks following the beginning of ET. Secondary endpoints include: endocrine toxicity/tolerability and quality of life measured respectively by the change in total score and individual items of FACT-ES and FACT-B (a validated Functional Assessment of Cancer Therapy for patients with a Breast cancer) from baseline to 4, 8, 12 and 52 weeks following the beginning of ET, rates of non-persistence or non-compliance and cost-effectiveness. A timing preference questionnaire will be filled out at the beginning and the end of the study by patients to evaluate their preferred time. As per the Rethinking Clinical Trials (REaCT) program, the integrated consent model will be used and patients will complete questionnaires in the online patient portal. For randomization, a permuted block design developed by the Ottawa Methods Centre will be used and patients will be stratified by center, type of endocrine therapy (tamoxifen yes/no) and if prior chemotherapy was received. Using a two-sided, alpha=0.05 Fisher’s exact test, and assuming a 10% of loss to follow up, the planned sample size is 235 patients. Accrual. This study opened for enrollment at The Ottawa Hospital Cancer Centre on June 30, 2021 and will open soon at the Thunder Bay Regional Health Sciences Centre. The maximum accrual period is 2 years. Conclusion. This will be world’s first prospective randomized clinical trial to evaluate ET dose timing (morning versus evening) and its effects on tolerability and adherence. Changing the time of the day at which a medication is taken is a new, simple and easy intervention that does not generate additional costs and can improve the quality of life of breast cancer patients. Funding provided by: NOAMA (Northern Ontario Academic Medicine Association) Innovation Grant (2021) Clinical Trial Registration: NCT04864405 Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Ana-Alicia Beltran-Bless, Lesley Fallowfield, Mark Clemons. A pragmatic, randomised, multicentre trial evaluating the dose timing (morning vs evening) of endocrine therapy and its effects on tolerability and compliance (REaCT-CHRONO Study) [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 OT1-11-02.

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 P4-11-24: Patient's point of view on how to promote adherence to adjuvant endocrine therapy (ET): A large french survey

Abstract Purpose: Non-adherence to adjuvant ET remains a major issue in patients with localized breast cancer (BC) and negatively impacts the long-term recurrence and survival outcomes. Recently, we reported that 16.0% of premenopausal pts had a serum tamoxifen level below the set adherence threshold and had an increased their risk of breast cancer distant recurrences (NCT01993498). Thus, implementation of personalized effective strategies to improve patients adherence remains a topic of active research. As effective approaches must rely upon a comprehensive understanding of the multiple interplaying factors that affect adherence, we performed a survey among French breast cancer survivors that were receiving or had previously received adjuvant ET to explore patients’ expectations and preferences for mitigating ET side effects. Methods: From July 1st to July 31 2020, we addressed a large social media and web-based survey to premenopausal patients who currently or had been treated for a localised BC in collaboration with 2 major French patient advocacy groups “Les Seintinelles” and “ODYSSEA Foundation”. The survey aimed to determine: a. patient’s preferences on ET formulation and administration; b. patient’s opinion on the contents of a mobile application for managing ET. It comprised 3 items: information about the participants and the ET received or currently ongoing; preferences on ET formulation (type of pill, taste, color, shape), dosing and combination with active drugs controlling side effects; opinion on the usefulness of a mobile application and relevance of its possible contents for complementing ET administration. Results: Of the 1,616 survey responses collected, 1,474 were completely filled and could be used in the analysis. 65% of them were aged between 40 and 59 years, 68% were still receiving ET during data collection. Most of the patients considered the presentation of the drug (taste, shapes and colors) to have little impact on adherence to treatment. The preferred pharmaceutical forms were capsules or swallowable tablets (56%). 75% of participants favoured a single pill containing ET plus an active substance controlling side effects. 85% were favourable to the use of a mobile application, in particular to better understand the interest and the expected benefit of ET (15%), to be reminded when to take the treatment (11%), and to obtain advice concerning the management of side effects (29%).Conclusion: This large French survey identified two main leads that could potentially promote or improve adherence to ET: combined treatment formulation including substances. targeting side effects, and a mobile application allowing support throughout treatment duration. Patient’s opinions on ET dosing and management are essential to inform the development of personalized approaches for improving adherence. Keywords: Endocrine therapy, non-adherence, breast-cancer, survey. Citation Format: Sarra Akla, Elie Rassy, Antonio Di-Meglio, Elise Martin, Julie Havas, Andre Rieutord, Angelo Paci, David Combarel, Leonor Fasse, Florian Scotte, Guillemette Jacob, Anne Bergognoux, Suzette Delaloge, Ines Vas Luis, Barbara Pistilli. Patient's point of view on how to promote adherence to adjuvant endocrine therapy (ET): A large french survey [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 P4-11-24.

Abstract P4-09-05: Focus on non-adherence: A qualitative exploration of perceptions associated to adjuvant endocrine therapy (ET) in premenopausal patients with breast cancer and their health care providers (HCP)

Abstract Background and Objectives: Despite the proven benefits on reducing time to recurrence and improving survival, recent studies indicate that only half or less of patients with early stage breast cancer (BC) complete their recommended full-course of adjuvant ET. Findings suggested that adherence therefore remains a challenge for both patients and professionals, with differences in representations that remain poorly understood. The main objective of this study is to investigate BC patient’s perceptions about ET. Secondary objectives are: (1): to capture potential gaps between their perceptions and the representations of their HCP (2): to explore preferences in patients regarding programs aimed to improve adherence to ET. Methods We conducted separately focus groups with patients and HCP to capture a multilevel framework regarding non-adherence. Inclusion criteria for patients’ focus groups were: non metastatic hormone-receptor positive (HR+) BC; ≥18 years old; premenopausal at time of diagnosis; receiving ET for at least 2 months; for HCP criteria were: to be a medical oncologist, radiation oncologist, pharmacist or nurse; with at least 5 years of experience on BC. The discussion schedule was non-directive and included: introduction remarks and three key- questions linked to our objectives as well as follow-up questions to facilitate the discourse. Discussions were audio recorded, anonymized and transcribed verbatim. We used a thematic analysis approach to identify patterns and themes. Results: Twenty-eight patients (median age=45 yrs) and 17 professionals (11 women, median professional experience with BC =9.5 yrs) participated. Major themes emerging among participants are showed in Table 1. Important differences between HCP and patients with BC were analyzed regarding their representations towards adherence and communication.Conclusions: Dissatisfaction concerning ET medical monitoring and communication is shared by patients and professionals. The HCP reported a lack of communication skills to support patients struggling with ET adherence. Strikingly, the major barrier to ET reported by patients is related to the employment and the lack of adaptation to sequelae of ET. This barrier is not reported by professionals and appears a critical challenge to face. The suggestions made by patients during the focus groups offer promising perspectives regarding support programs to improve adherence. PatientsN=28Major themesSub-themes•Representations on ET : a multidimensional burden1.Side effects and management2.Benefit/risk balance 3.Seeking information on ET•Professional life1.Work reintegration2.Lack of empathy of coworkers3.Career change•Psychological adjustment to ET1.Daily struggling2.Self-image modifications3.Feelings of loneliness•Relations to health care providers1.Communication: negative and positive aspects2.Shared decision-making 3.Advice on follow-up careHCP (N=17)•Representations on ET : a therapeutic weapon1.Side effects 2.Impact on body image 3.Finding solutions regarding ET side effects•Discourse to patients1.Negotiating the adherence to treatment 2.Beliefs on patients’ suggestibility 3.Communication techniques•Emotional experience: negative impact of prescribing ET1.Emotional fatigue2.Guilt 3.Desire on having psychologists to handle the patients’ emotions•Difficulties related to the healthcare system1.Lack of time 2.Lack of training Citation Format: Léonor Maria Fasse, Nicolas Roche, Diane Boinon, Gwenn Menvielle, Agnes Dumas, Sofia Rivera, Margarida Matias, Antonio Di-Meglio, Suzette Delaloge, Ines Vaz-Luis, Barbara Pistilli. Focus on non-adherence: A qualitative exploration of perceptions associated to adjuvant endocrine therapy (ET) in premenopausal patients with breast cancer and their health care providers (HCP) [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 P4-09-05.

Outcome without any adjuvant systemic treatment in stage I ER+/HER2− breast cancer patients included in the MINDACT trial

Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST.Patients with estrogen receptor-positive, HER2-negative, lymph node-negative tumors ≤2 cm who received no AST were matched 1 : 1 to patients with similar tumor characteristics treated with adjuvant endocrine therapy (ET), using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade. In a post hoc analysis, distant metastasis-free interval (DMFI) and overall survival (OS) were assessed by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence (LRR) and contralateral breast cancer (CBC) were assessed with competing risk analyses.At 8 years, DMFI rates were 94.8% [95% confidence interval (CI) 92.7% to 96.9%] in 509 patients receiving no AST, and 97.3% (95% CI 95.8% to 98.8%) in 509 matched patients who received only ET [absolute difference: 2.5%, HR 0.56 (95% CI 0.30-1.03)]. No statistically significant difference was seen in 8-year OS rates, 95.4% (95% CI 93.5% to 97.4%) in patients receiving no AST and 95.6% (95% CI 93.8% to 97.5%) in patients receiving only ET [absolute difference: 0.2%, HR 0.86 (95% CI 0.53-1.41)]. Cumulative incidence rates of LRR and CBC were 4.7% (95% CI 3.0% to 7.0%) and 4.6% (95% CI 2.9% to 6.9%) in patients receiving no AST versus 1.4% (95% CI 0.6% to 2.9%) and 1.5% (95% CI 0.6% to 3.1%) in patients receiving only ET.In patients with stage I low-risk breast cancer, the effect of ET on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received ET, after the relatively short follow-up of 8 years. These benefits and side-effects of ET should be discussed with all patients, even those at a very low risk of distant metastasis.