Role of Individualized Intervention(s) on Quality of Life and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer: MyCHOICE Study

Role of Individualized Intervention(s) on Quality of Life and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer: MyCHOICE Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Role of Individualized Intervention(s) on Quality of Life and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer: MyCHOICE Study Shahid Ahmed, Sonya Mannala, Prosanta Mondal, Wardah Mahmood, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8935918/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Premenopausal women receiving combination endocrine therapy often experience substantial declines in quality of life (QOL), cognitive functioning, and treatment adherence. The MyChoice study evaluated whether individualized behavioral and complementary interventions could help maintain or improve QOL and treatment adherence in women with early-stage hormone receptor–positive breast cancer undergoing aromatase inhibitor- or tamoxifen-based therapy with ovarian suppression. Methods MyChoice was a prospective multicenter phase II study in which participants selected tailored supportive interventions, including structured exercise programs, restorative yoga, acupuncture, and massage therapy. QOL and cognitive function were assessed at baseline, 3 months, and every 6 months for up to 3 years using FACT-B, FACT-ES, and FACT–Cognitive Function instruments. Longitudinal changes were analyzed using linear mixed-effects models. Other outcomes included treatment adherence and demographic or clinical predictors of QOL. Results Forty premenopausal women participated, with a median age of 43 years. Exercise was the most frequently selected intervention (61%), followed by massage therapy (44%) and acupuncture (35%). Functional well-being improved significantly over time (1.42 points/year, p = 0.01). Emotional well-being, social/family well-being, physical well-being, endocrine symptoms, and perceived cognitive abilities remained stable. Adherence to endocrine therapy was high at 92.5% over follow-up period. In multivariable models, younger age (< 35 years) was associated with higher symptom burden across several domains, while functional well-being improved steadily with time. Conclusion Individualized, patient-selected supportive interventions may help maintain or improve key aspects of QOL, stabilize cognitive function, and support high adherence to endocrine therapy in premenopausal women with early-stage breast cancer. These findings support further evaluation in larger controlled trials. Premenopausal breast cancer endocrine therapy adherence quality of life supportive care complementary interventions Figures Figure 1 Figure 2 INTRODCUTION Breast cancer is among the most frequently diagnosed malignancies in women ( 1 , 2 ). Globally, an estimated 2.3 million women are diagnosed with breast cancer each year, making it the most commonly diagnosed cancer worldwide ( 3 ). Advances in screening, surgical procedures, radiation, and systemic therapies have rendered breast cancer one of the most treatable solid tumors, significantly lowering both recurrence and mortality rates ( 4 – 6 ). However, these treatments are often associated with acute and long-term side effects that can markedly diminish quality of life (QOL) [5,7–9]. Approximately 70–80% of breast cancer cases express hormone receptors, being estrogen receptor (ER)–positive and/or progesterone receptor (PR)–positive ( 10 ). In these patients, adjuvant endocrine therapy, commonly referred to as anti-estrogen therapy, has been associated with a significant reduction in the risk of recurrence and breast cancer-specific mortality ( 11 ). Endocrine therapy may be administered alone or following chemotherapy in patients considered high-risk. Notably, approximately 25% of breast cancer cases are diagnosed in women under the age of 50 ( 12 ). Younger survivors are especially prone to experiencing physical, emotional, and psychosocial sequelae from treatment ( 13 ). Available adjuvant endocrine therapy options for premenopausal women include tamoxifen, ovarian suppression alone, or a combination of ovarian suppression with tamoxifen or an aromatase inhibitor ( 4 , 6 ). Findings from the randomized clinical trials support that ovarian suppression combined with exemestane, an aromatase inhibitor, or tamoxifen is more effective than tamoxifen alone in premenopausal women at high risk of recurrence or those under 35 years of age ( 14 – 16 ). Nonetheless, the combination of an aromatase inhibitor and ovarian suppression has been associated with a higher incidence of adverse effects such as bone loss, musculoskeletal complaints, vaginal dryness, reduced libido, dyspareunia, resulting in early therapy discontinuation. Furthermore, adding ovarian suppression to tamoxifen can increase menopausal symptoms and has been associated with more than a 20% reduction in self-reported health-related quality of life ( 17 , 18 ). In addition, adjuvant endocrine therapy may negatively affect cognitive function in women with early-stage breast cancer ( 19 ). While adherence to endocrine therapy is critical for minimizing recurrence and improving survival, reported adherence rates among breast cancer survivors vary considerably, ranging from 50% to 92% ( 20 – 23 ). QOL is defined as a person’s self-perceived well-being influenced by disease and its treatment ( 24 ). Health-related QOL is essential for cancer survivorship and encompasses multiple dimensions, including physical, emotional, and social well-being, as well as potentially cognitive function, sexuality, and spirituality. Various behavioral and complementary strategies including regular physical activity, yoga, acupuncture, dietary interventions, and massage therapy have demonstrated benefits in mitigating treatment-related side effects and enhancing QOL ( 5 , 25 – 27 ). For example, physical activity has been shown to improve both physical and mental health among cancer survivors. Personalized exercise programs can help enhance treatment tolerance, alleviate fatigue, improve sleep and cognitive function, and reduce depression associated with breast cancer therapies ( 28 ). Similarly, yoga has been found to alleviate treatment-related symptoms and improve mental well-being and QOL in women with breast cancer ( 29 , 30 ). Acupuncture has also shown effectiveness as a supportive therapy for managing hot flashes and improving QOL in this population ( 21 , 32 ). Although a variety of such interventions appear promising, the overall quality of evidence remains limited. Adaptive interventions are individualized approaches tailored to each patient’s specific needs. While numerous behavioral and complementary interventions have been evaluated in breast cancer patients, limited research exists on their role in maintaining QOL and adherence to endocrine therapy specifically among younger women receiving combination endocrine treatment. Self-management is defined as the tasks individuals undertake to cope with the medical, emotional, and functional challenges posed by their health conditions ( 33 ). Selecting appropriate behavioral or complementary interventions based on side effects, usability, personal preferences, and contextual considerations may facilitate a self-management approach, promote patient empowerment, and thereby maintain treatment tolerance and QOL. The MyChoice study was designed to evaluate whether individualized adaptive behavioral and complementary interventions can maintain or improve treatment tolerance and adherence in younger women with early-stage breast cancer receiving combination endocrine therapy (aromatase inhibitor or tamoxifen in conjunction with ovarian suppression). The primary objectives were to assess whether personalized interventions can mitigate declines in QOL and self-reported cognitive function and to evaluate their impact on treatment discontinuation. Secondary objectives included identifying socio-demographic and clinical factors associated with QOL METHODS MyChoice was a single-arm multi-center prospective phase II trial. The study was approved by the University of Saskatchewan Biomedical Research Ethics Board (Bio 17–239) and by the Saskatchewan Cancer Agency Data Access Committee. The trial was registered at ClinicalTrials.gov (NCT03407768). Informed consent was obtained from all participants. Given that combination endocrine therapy is associated with a reduction of over 20% in quality of life (QOL) scores, we hypothesized that individualized interventions would result in less than a 20% decline from baseline (i.e., either maintained or improved QOL). Using an alpha of 0.05 and a power of 80%, the required sample size was estimated at 40 participants. Eligible participants were premenopausal women with completely resected, hormone receptor–positive stage I, II, or III invasive breast cancer, who were undergoing treatment with combination endocrine therapy. The study participants were enrolled at the two main tertiary cancer centers in the province of Saskatchewan, Canada. Interventions Participants were offered a range of supportive interventions aimed at improving recovery from treatment-related side effects and enhancing tolerance to hormonal therapy. Each participant was free to select one or more interventions, or to decline them entirely, based on individual preference. Participants opting for the individualized exercise program received a guidebook titled “Exercise for Health,” designed for breast cancer survivors, along with a physical activity tracker. They participated in individual consultations with a certified personal trainer, scheduled periodically during the first 6–12 months of treatment. These sessions focused on developing and adapting a personalized exercise plan based on the participant’s fitness level, preferences, and any physical or logistical barriers to activity. Participants choosing yoga and mindfulness were enrolled in a six-week restorative yoga program designed to address fatigue, anxiety, depression, and other symptoms. The program emphasized mindfulness, resilience-building, and strengthening the mind–body connection to support emotional and physical recovery. Those selecting massage therapy were referred to licensed massage therapists, with treatment techniques and frequency tailored to individual needs. Similarly, participants interested in acupuncture were referred to certified practitioners, and the number and frequency of sessions were personalized. Participants who did not choose any of the listed interventions but expressed interest in other complementary therapies were provided with educational resources relevant to their preferences. Health-related Quality of Life and Self-reported Cognitive Function Participants completed validated surveys assessing menopausal symptoms, sexual function, general well-being, and cognitive function. QOL was measured using the Functional Assessment of Cancer Therapy, Breast Symptom Index (FACT-B, version 4) and the Functional Assessment of Cancer Therapy, Endocrine Symptoms (FACT-ES, version 4) ( 34 ). FACT-B includes items across six domains: physical well-being, social/family well-being, emotional well-being, functional well-being, relationship with the physician, and additional concerns, rated on a five-point Likert scale from 0 (not at all) to 4 (very much). FACT-ES includes 18 items focused on endocrine-related symptoms, particularly menopausal and sexual issues associated with breast cancer treatment. Self-reported cognitive function was assessed using the FACT–Cognitive Function (version 3), a validated subjective tool designed to evaluate perceived cognitive decline among cancer patients. Patient-reported outcomes were assessed at baseline, 3 months, and every 6 months thereafter, for up to three years following enrollment. Statistical Analysis Descriptive data were presented as mean (standard deviation) or median (range). Longitudinal changes in overall QOL and its domains were evaluated using linear mixed-effects models. Demographic and clinical variables, including ethnicity, age (< 35 vs. ≥35 years), body mass index, education level, marital status, and type of surgery, were analyzed for their association with QOL. Regression analyses were used to examine correlations between QOL, self-reported cognitive function, and other variables. All statistical analyses were conducted using linear mixed-effects modeling (SAS 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS Forty premenopausal women were enrolled in the study between October 2018 and September 2019, with a median age of 43 years (range 26–55). One patient was excluded from the QOL analysis after being found to have metastatic disease shortly after enrollment. The majority of participants were Caucasian (82%), with smaller proportions identifying as Indigenous, Black, or Asian (each 5% or less). Forty percent had a university degree, and over half were either married (53%) or in a common law relationship (7%). Most participants (73%) had children (Table 1 ). Among the study participants, 30 (75%) received chemotherapy, including 20% who received neoadjuvant chemotherapy. Trastuzumab was administered to 8 patients (20%), one of whom had HER2-equivocal disease. A total of 80% of patients had T2 or node-positive disease, and 18% were HER2-positive. Thirty-six patients (90%) underwent adjuvant radiation therapy (Table 2 ). Table 1 Baseline Demographic Characteristics of Study Participants Baseline N (%) Race Caucasian 28 (82) Indigenous 2 ( 5 ) Black 2 ( 5 ) Asian 2 ( 2 ) Not reported 6 ( 15 ) Education High school 8 ( 20 ) College 9 ( 23 ) University degree 16 (40) Not reported 7 ( 17 ) Relationship Married 21 (53) Common law relationship 3 ( 7 ) Single 9 ( 23 ) Not reported 7 ( 17 ) Children Yes 29 (73) No 5 ( 12 ) Not reported 6 ( 15 ) Table 2 Clinical and Treatment Characteristics of Study Participants Variable N = 40 (%) Median age 43 years (range: 26–55 years) Comorbid illness 12 ( 30 ) No pregnancy 7 (18%) Median pregnancy 2 T status T1 14 ( 35 ) T2 20 (50) T3 5 ( 13 ) T4 1 ( 3 ) Median size 23 mm (10–86 mm) N status N0 11 ( 28 ) N1 11 ( 28 ) N2 15 (38) N3 3 ( 8 ) Surgery Lumpectomy 14 ( 35 ) Mastectomy 26 (65) Bilateral mastectomy 17 (43) Received chemotherapy 30 (75) Adjuvant 22 (73) Neoadjuvant 8 ( 27 ) Adjuvant trastuzumab 8 ( 20 ) Adjuvant radiation 36 (90) Adjuvant endocrine therapy Exemestane plus ovarian suppression 16 (40) Anastrozole plus ovarian suppresion 13 ( 33 ) Letrozole plus goserelin 9 ( 23 ) Tamoxifen plus goserelin 2 ( 5 ) * 36 women received goserelin Among patients with T1N0 HR+/HER2-negative disease, all had high or intermediate Oncotype DX recurrence scores. Twenty-two patients (55%) received a combination of anthracycline- and taxane-based chemotherapy regimens, including dose-dense AC followed by paclitaxel, or FEC-100 followed by docetaxel or paclitaxel. An additional 8 patients (20%) received 4 to 6 cycles of adjuvant docetaxel and cyclophosphamide. Endocrine therapy consisted of exemestane in 40% of patients, anastrozole in 32%, letrozole in 23%, and tamoxifen in 5%, all combined with ovarian suppression. Thirty-six patients (90%) received goserelin, a gonadotropin-releasing hormone (GnRH) analog, while 4 (10%) underwent upfront oophorectomy. An additional 21 patients (53%) later underwent bilateral oophorectomy, bringing the total number of women who ultimately received surgical ovarian suppression to 25 (63%) Across the cohort, exercise-based strategies were the most frequently selected intervention, with approximately 61% of participants choosing some form of physical activity, ranging from mild to strenuous exercise with an exercise trainer. Massage therapy represented the second most common choice, selected by 44% of participants, followed by acupuncture, which was used by 35% of women. Overall, about 65% of participants opted for a single supportive intervention, whereas 35% engaged in combinations involving more than one intervention with approximately 9% utilizing more than two interventions. Results from the linear mixed-effects model indicated a statistically significant improvement in functional well-being, which increased by 1.65 points per year (p < 0.001), reflecting better day-to-day functioning (Fig. 1 A). Emotional well-being showed a non-significant improvement, with a decrease of 0.26 points per year (p = 0.14), suggesting reduced emotional distress over time (Figure IB; Table 3 ). Social/family well-being showed a non-significant increase of 0.34 points per year (p = 0.18). The total FACT-ES score, where higher scores indicate greater endocrine-related symptom burden, decreased by 0.72 points per year, suggesting a potential reduction in symptoms; however, this change was not statistically significant (p = 0.18) [Figure 2 B]. Physical well-being and perceived cognitive abilities remained stable, with no significant changes observed over time (p = 0.96 and p = 0.61, respectively). Over a 60-month follow-up period, 92.5% of patients remained adherent to adjuvant endocrine therapy. Four participants (10%) experienced disease recurrence, and two (5%) died during follow-up. Taken together, these findings indicate that individualized interventions may help mitigate declines in quality of life and cognitive function during endocrine therapy and may support continued treatment adherence. Table 3 Linear mixed-effects (LME) model Outcome Estimate (standard error) P-value Total FACT-ES -0.20 (0.54) 0.71 Total Functional Well-Being 1.65 (0.43) 0.0005 Total Emotional Well-being -0.26 (0.18) 0.14 Total Social/Family Well-Being 0.13 (0.39) 0.74 Total Physical Well-Being -0.53 (0.40) 0.19 Perceived Cognitive Abilities 0.11 (0.65) 0.86 During the study period, functional well-being significantly improved by 1.65 ± 0.43 points per year (p = 0.0005). Emotional well-being improved by 0.26 ± 0.18 points per year (p = 0.14). Total FACT-ES (–0.20 ± 0.54; p = 0.71), social/family well-being (0.13 ± 0.39; p = 0.74), physical well-being (-0.53 ± 0.40; p = 0.19), and perceived cognitive abilities (0.11 ± 0.65; p = 0.86) remained stable over time In the multivariable analysis, younger age (< 35 years) was consistently associated with poorer outcomes across several domains. Younger women reported higher FACT-ES total scores (Estimate = 8.76, SE = 3.89, p = 0.02), greater perceived cognitive impairment (Estimate = 13.76, SE = 7.16, p = 0.05), more negative comments from others (Estimate = 5.01, SE = 0.81, p < 0.0001), and a greater overall impact on quality of life (Estimate = 4.99, SE = 1.56, p = 0.001). Participants identifying as Caucasian reported lower functional well-being (Estimate = − 3.39, SE = 1.71, p = 0.05) and lower perceived cognitive abilities (Estimate = − 7.90, SE = 2.66, p = 0.003) compared with other racial groups. Marital status demonstrated a protective association in one domain, with married participants reporting fewer negative comments from others (Estimate = − 1.89, SE = 0.69, p = 0.007). DISCUSSION Premenopausal women undergoing combination endocrine therapy often experience substantial treatment-related challenges that can negatively affect quality of life, cognitive function, and long-term adherence ( 13 ). The MyChoice study was designed to address this need by offering a flexible, patient-centered model in which women selected individualized behavioral and complementary interventions tailored to their symptoms, preferences, and readiness for engagement. This approach aimed to support self-management, promote resilience, and ultimately maintain treatment tolerance and adherence throughout the course of adjuvant endocrine therapy. The findings from this study provide encouraging evidence that individualized supportive interventions can help preserve, and even enhance, several aspects of well-being during intensive endocrine therapy. Functional well-being improved significantly over time, suggesting that targeted exercise guidance and structured activity planning may have contributed to enhanced energy, daily functioning, and overall physical capability ( 27 , 28 ). Emotional well-being also improved, consistent with benefits previously reported from mindfulness-based practices, yoga, and other mind–body interventions that help women cope with stress, anxiety, and the emotional burden of treatment. Social and endocrine symptom domains showed favorable, though not statistically significant, trends toward improvement. Importantly, physical well-being and cognitive abilities remained stable, which is notable given that declines are commonly observed in premenopausal women receiving aromatase inhibitors with ovarian suppression ( 13 , 19 ). The maintenance of these domains indicates that supportive interventions may mitigate the typical deterioration expected from endocrine therapy alone. Adherence outcomes in this cohort were particularly noteworthy. Over a follow-up period of 60 months, more than 90% of participants remained adherent to endocrine therapy, a rate that exceeds adherence reported in many other studies. This high level of persistence suggests that individualized supportive care may play an important role in sustaining engagement with treatment, ultimately enhancing long-term disease control. Multivariable analyses identified several patient characteristics that appeared to be associated with quality-of-life outcomes. Younger women reported greater symptom burden and more cognitive concerns, consistent with prior evidence that this subgroup may face increased challenges during endocrine therapy. These observations reinforce the importance of considering tailored supportive strategies that address the specific needs of younger patients. Exploratory differences by race and marital status further suggest that women’s experiences throughout treatment may be influenced not only by clinical factors but also by their broader social and cultural environments. The tendency for married participants to report fewer negative comments from others may reflect stronger partner-based social support, which has been shown to positively influence coping and psychosocial adjustment in women with breast cancer ( 35 , 36 ). Although based on a modest sample size, the gradual improvement observed in functional well-being over time suggests a potential cumulative benefit of continued engagement in supportive interventions. A major strength of the MyChoice study is its individualized, adaptive intervention model, which allowed participants to select therapies aligned with their needs, preferences, and side-effect profiles. This patient-centered approach likely enhanced acceptability and engagement by empowering participants and promoting self-management. Such flexibility mirrors real-world clinical practice more closely than structured, uniform intervention protocols and highlights a feasible pathway for integrating complementary support into routine oncology care. The study also has limitations that should be acknowledged. The absence of a control group limits definitive conclusions about causality, and the modest sample size may reduce the power to detect smaller but meaningful changes in some quality-of-life domains. Variation in participants’ uptake and adherence to supportive therapies may also have influenced outcomes in ways not fully captured in the analyses. Nonetheless, these limitations are consistent with a phase II exploratory design, and the findings provide a strong foundation for future controlled trials. Overall, the MyChoice study demonstrates that individualized behavioral and complementary interventions may help maintain or improve key aspects of quality of life in premenopausal women receiving combination endocrine therapy. The improvements observed in functional and emotional well-being, coupled with the stability of physical and cognitive outcomes and the high rate of treatment adherence, support the value of integrating personalized supportive care into standard breast cancer management. These promising results justify further evaluation in a larger, randomized trial to more definitively assess the impact of tailored, patient-driven supportive interventions on survivorship outcomes. In conclusion, the integration of personalized supportive care into standard oncology practice represents a promising avenue to optimize survivorship in young breast cancer patients. MyChoice highlights that empowerment through choice, coupled with holistic support, can lead to measurable improvements in quality of life making the cancer journey more tolerable and potentially more successful. Declarations FUND This work was funded by a research grant from the College of Medicine, University of Saskatchewan (CMRAD 419711). Author Contribution S.A. (Shahid Ahmed) conceived and designed the study, secured funding, supervised the project, and critically revised the manuscript. S.M. (Sonya Mannala) and W.M. contributed to data collection, study coordination, and manuscript preparation. P.M. performed statistical analyses and contributed to data interpretation. L.D., D.G.L., S.K., A.C., and A.L. contributed to study methodology, implementation of supportive interventions, and interpretation of results. N.I., M.S., M.I.K., O.A., M.M., A.B., K.H., H.I.C., and A.S. (Amer Sami) contributed to patient recruitment, clinical data acquisition, and manuscript review.All authors reviewed, edited, and approved the final manuscript. Acknowledgement The authors express their sincere gratitude to all the patients who participated in the MyChoice study for their willingness to share their experiences and for their invaluable contributions. We also thank the Saskatchewan Breast Cancer Tumor Group whose engagement and advocacy helped facilitate study awareness and patient involvement. The Saskatchewan Cancer Agency provided essential clinical and administrative support, including the dedicated efforts of its Clinical Trials Unit. We further extend our appreciation to the College of Medicine at the University of Saskatchewan for providing funding and support of this research. Data Availability The datasets generated and analyzed during the current study are stored in the institutional electronic data capture platform REDCap hosted at the University of Saskatchewan. Due to ethical and privacy restrictions, the data are not publicly available. Access to the data may be granted upon reasonable request and with appropriate approval from the University of Saskatchewan Research Ethics Board (USASK REB) and the Saskatchewan Cancer Agency, in accordance with institutional policies and data governance regulations. 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Belau MH, Jung L, Maurer T, Obi N, Behrens S, Seibold P, Becher H, Chang-Claude J. Social relationships and their impact on health-related quality of life in a long-term breast cancer survivor cohort. Cancer. 2024 Sep 15;130(18):3210-3218. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8935918","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606821683,"identity":"df589eda-f162-4871-b860-996b5ad23fed","order_by":0,"name":"Shahid Ahmed","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFUlEQVRIiWNgGAWjYDACCQY2hgQ2BgYDEPsDWIAULZIziNbCANUizUOMFvnZzc8ePChjkDcXO3zwts0fO3vJ9sPPHvyouMfA334AqxaDO8fMDRLOMRjunJ2WbJ3blpw4myfN3LDnTDGDxJkE7FokEswkEtsYGDfczjGTzm1gTpCTYDCTZmxLADoVuxb5GenfQFrsN9zO/yZt8afeXk6C/Zs04z+gFv4H2D1zIwdsSyLQFjZpBrbDjLMleIC2NCSAHIDdYTdyyiQSzkkkb7idZmzZ23Y8cWZPTplkz7EEHokb2G0BOmyb5I8yG9sNt5Mf3vjxp9pe4vjxbRI/ahLk+Pux2wIFWCKDB5/6UTAKRsEoGAX4AQDgX1k8j1w22AAAAABJRU5ErkJggg==","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":true,"prefix":"","firstName":"Shahid","middleName":"","lastName":"Ahmed","suffix":""},{"id":606821684,"identity":"fad09059-7aba-444f-a26d-acfef1277f88","order_by":1,"name":"Sonya Mannala","email":"","orcid":"","institution":"University of Saskatchewan","correspondingAuthor":false,"prefix":"","firstName":"Sonya","middleName":"","lastName":"Mannala","suffix":""},{"id":606821685,"identity":"f05c5277-147d-4c96-9644-d1658d9801c6","order_by":2,"name":"Prosanta Mondal","email":"","orcid":"","institution":"University of Saskatchewan","correspondingAuthor":false,"prefix":"","firstName":"Prosanta","middleName":"","lastName":"Mondal","suffix":""},{"id":606821686,"identity":"b75eda69-0783-4e41-bc4b-bd183e37a506","order_by":3,"name":"Wardah Mahmood","email":"","orcid":"","institution":"University of Saskatchewan","correspondingAuthor":false,"prefix":"","firstName":"Wardah","middleName":"","lastName":"Mahmood","suffix":""},{"id":606821687,"identity":"624914bc-54c8-4a0a-9ae1-03ddc5393c9b","order_by":4,"name":"Haji Ibrahim Chalchal","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Haji","middleName":"Ibrahim","lastName":"Chalchal","suffix":""},{"id":606821688,"identity":"51261990-b480-46af-a70b-dd36f2e1cdd8","order_by":5,"name":"Lynn Dwernychuk","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Lynn","middleName":"","lastName":"Dwernychuk","suffix":""},{"id":606821689,"identity":"bbda162f-22f5-4fd4-9980-fe10b2ee40cd","order_by":6,"name":"Nayyer Iqbal","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Nayyer","middleName":"","lastName":"Iqbal","suffix":""},{"id":606821690,"identity":"0e65b340-d068-40e1-b0f8-6d0d7a391d17","order_by":7,"name":"Muhammad Salim","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Salim","suffix":""},{"id":606821691,"identity":"49aa3b7a-af90-46cb-ade0-e602536d3157","order_by":8,"name":"Muhammad Imtiaz Khan","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Imtiaz","lastName":"Khan","suffix":""},{"id":606821692,"identity":"950fbaa0-838d-4719-b3a6-e96c3e874f23","order_by":9,"name":"Osama Ahmed","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"","lastName":"Ahmed","suffix":""},{"id":606821693,"identity":"45d08b7a-b23a-4739-92b0-ce0292809589","order_by":10,"name":"Mita Manna","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Mita","middleName":"","lastName":"Manna","suffix":""},{"id":606821694,"identity":"c8f4d5ee-3f1f-4f89-99fb-33074ed36ca5","order_by":11,"name":"Donelda Gowan Leverick","email":"","orcid":"","institution":"University of Saskatchewan","correspondingAuthor":false,"prefix":"","firstName":"Donelda","middleName":"Gowan","lastName":"Leverick","suffix":""},{"id":606821695,"identity":"94b78b5f-e42f-447e-b711-4193f6fe3a6a","order_by":12,"name":"Ambika Chandrasekhar","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Ambika","middleName":"","lastName":"Chandrasekhar","suffix":""},{"id":606821696,"identity":"583f640f-40e3-4feb-bf37-3dba4f8f2118","order_by":13,"name":"Ayesha Bashir","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Ayesha","middleName":"","lastName":"Bashir","suffix":""},{"id":606821697,"identity":"de703de1-a05d-427a-a727-c88be6101260","order_by":14,"name":"Kamal Haider","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Kamal","middleName":"","lastName":"Haider","suffix":""},{"id":606821698,"identity":"45d24dce-c3e4-4214-9943-219a47724e9d","order_by":15,"name":"Anne Leis","email":"","orcid":"","institution":"University of Saskatchewan","correspondingAuthor":false,"prefix":"","firstName":"Anne","middleName":"","lastName":"Leis","suffix":""},{"id":606821699,"identity":"14595af6-89a3-49e2-9805-257471790c2e","order_by":16,"name":"Saija Kontulainen","email":"","orcid":"","institution":"University of Saskatchewan","correspondingAuthor":false,"prefix":"","firstName":"Saija","middleName":"","lastName":"Kontulainen","suffix":""},{"id":606821700,"identity":"6f60cf12-7686-410f-bd9c-7ed7241adcbd","order_by":17,"name":"Amer Sami","email":"","orcid":"","institution":"Saskatchewan Cancer Agency","correspondingAuthor":false,"prefix":"","firstName":"Amer","middleName":"","lastName":"Sami","suffix":""}],"badges":[],"createdAt":"2026-02-21 22:23:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8935918/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8935918/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104816431,"identity":"a74f6f49-0120-48d0-ae37-8eed0c63fe87","added_by":"auto","created_at":"2026-03-17 13:36:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":285266,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePredicted changes in Functional Well-Being over time as measured by the FACT-B. Values reflect model-predicted means over time. Higher scores indicate better functional well-being.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB: . Predicted changes in Emotional Well-Being from the FACT-B over time. Estimates represent model-predicted values over the study period. Higher scores indicate worse emotional well-being (greater emotional distress).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8935918/v1/219cc758f97fcf3afb7fe860.png"},{"id":104816429,"identity":"841400e7-8c65-475e-bf7f-a4b9b7e7f087","added_by":"auto","created_at":"2026-03-17 13:36:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":220438,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA: Predicted changes in Perceived Cognitive Abilities over time as assessed by the FACT-Cognitive Function scale. Values shown are model-predicted means over time. Higher scores indicate better perceived cognitive abilities.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB: Predicted changes in endocrine symptoms (FACT-ES) over time measured by the FACT-ES. Trajectories represent model-based predicted scores across time. Higher scores indicate worse endocrine-related symptoms.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8935918/v1/2ffc3f47b15c0ba50f9ff4f8.png"},{"id":105903912,"identity":"cd59fc34-5352-4bb2-9a2c-a9451e2bd22a","added_by":"auto","created_at":"2026-04-01 09:57:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1432751,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8935918/v1/110a3509-ac09-4e85-9dd1-68dca5ff478a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eRole of Individualized Intervention(s) on Quality of Life and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer: MyCHOICE Study\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODCUTION","content":"\u003cp\u003eBreast cancer is among the most frequently diagnosed malignancies in women (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Globally, an estimated 2.3\u0026nbsp;million women are diagnosed with breast cancer each year, making it the most commonly diagnosed cancer worldwide (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Advances in screening, surgical procedures, radiation, and systemic therapies have rendered breast cancer one of the most treatable solid tumors, significantly lowering both recurrence and mortality rates (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, these treatments are often associated with acute and long-term side effects that can markedly diminish quality of life (QOL) [5,7\u0026ndash;9].\u003c/p\u003e \u003cp\u003eApproximately 70\u0026ndash;80% of breast cancer cases express hormone receptors, being estrogen receptor (ER)\u0026ndash;positive and/or progesterone receptor (PR)\u0026ndash;positive (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In these patients, adjuvant endocrine therapy, commonly referred to as anti-estrogen therapy, has been associated with a significant reduction in the risk of recurrence and breast cancer-specific mortality (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Endocrine therapy may be administered alone or following chemotherapy in patients considered high-risk. Notably, approximately 25% of breast cancer cases are diagnosed in women under the age of 50 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Younger survivors are especially prone to experiencing physical, emotional, and psychosocial sequelae from treatment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Available adjuvant endocrine therapy options for premenopausal women include tamoxifen, ovarian suppression alone, or a combination of ovarian suppression with tamoxifen or an aromatase inhibitor (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFindings from the randomized clinical trials support that ovarian suppression combined with exemestane, an aromatase inhibitor, or tamoxifen is more effective than tamoxifen alone in premenopausal women at high risk of recurrence or those under 35 years of age (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Nonetheless, the combination of an aromatase inhibitor and ovarian suppression has been associated with a higher incidence of adverse effects such as bone loss, musculoskeletal complaints, vaginal dryness, reduced libido, dyspareunia, resulting in early therapy discontinuation. Furthermore, adding ovarian suppression to tamoxifen can increase menopausal symptoms and has been associated with more than a 20% reduction in self-reported health-related quality of life (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In addition, adjuvant endocrine therapy may negatively affect cognitive function in women with early-stage breast cancer (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). While adherence to endocrine therapy is critical for minimizing recurrence and improving survival, reported adherence rates among breast cancer survivors vary considerably, ranging from 50% to 92% (\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eQOL is defined as a person\u0026rsquo;s self-perceived well-being influenced by disease and its treatment (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Health-related QOL is essential for cancer survivorship and encompasses multiple dimensions, including physical, emotional, and social well-being, as well as potentially cognitive function, sexuality, and spirituality. Various behavioral and complementary strategies including regular physical activity, yoga, acupuncture, dietary interventions, and massage therapy have demonstrated benefits in mitigating treatment-related side effects and enhancing QOL (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). For example, physical activity has been shown to improve both physical and mental health among cancer survivors. Personalized exercise programs can help enhance treatment tolerance, alleviate fatigue, improve sleep and cognitive function, and reduce depression associated with breast cancer therapies (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Similarly, yoga has been found to alleviate treatment-related symptoms and improve mental well-being and QOL in women with breast cancer (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Acupuncture has also shown effectiveness as a supportive therapy for managing hot flashes and improving QOL in this population (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Although a variety of such interventions appear promising, the overall quality of evidence remains limited.\u003c/p\u003e \u003cp\u003eAdaptive interventions are individualized approaches tailored to each patient\u0026rsquo;s specific needs. While numerous behavioral and complementary interventions have been evaluated in breast cancer patients, limited research exists on their role in maintaining QOL and adherence to endocrine therapy specifically among younger women receiving combination endocrine treatment. Self-management is defined as the tasks individuals undertake to cope with the medical, emotional, and functional challenges posed by their health conditions (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Selecting appropriate behavioral or complementary interventions based on side effects, usability, personal preferences, and contextual considerations may facilitate a self-management approach, promote patient empowerment, and thereby maintain treatment tolerance and QOL.\u003c/p\u003e \u003cp\u003eThe MyChoice study was designed to evaluate whether individualized adaptive behavioral and complementary interventions can maintain or improve treatment tolerance and adherence in younger women with early-stage breast cancer receiving combination endocrine therapy (aromatase inhibitor or tamoxifen in conjunction with ovarian suppression). The primary objectives were to assess whether personalized interventions can mitigate declines in QOL and self-reported cognitive function and to evaluate their impact on treatment discontinuation. Secondary objectives included identifying socio-demographic and clinical factors associated with QOL\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eMyChoice was a single-arm multi-center prospective phase II trial. The study was approved by the University of Saskatchewan Biomedical Research Ethics Board (Bio 17\u0026ndash;239) and by the Saskatchewan Cancer Agency Data Access Committee. The trial was registered at ClinicalTrials.gov (NCT03407768). Informed consent was obtained from all participants. Given that combination endocrine therapy is associated with a reduction of over 20% in quality of life (QOL) scores, we hypothesized that individualized interventions would result in less than a 20% decline from baseline (i.e., either maintained or improved QOL). Using an alpha of 0.05 and a power of 80%, the required sample size was estimated at 40 participants. Eligible participants were premenopausal women with completely resected, hormone receptor\u0026ndash;positive stage I, II, or III invasive breast cancer, who were undergoing treatment with combination endocrine therapy. The study participants were enrolled at the two main tertiary cancer centers in the province of Saskatchewan, Canada.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eInterventions\u003c/h2\u003e \u003cp\u003eParticipants were offered a range of supportive interventions aimed at improving recovery from treatment-related side effects and enhancing tolerance to hormonal therapy. Each participant was free to select one or more interventions, or to decline them entirely, based on individual preference. Participants opting for the individualized exercise program received a guidebook titled \u0026ldquo;Exercise for Health,\u0026rdquo; designed for breast cancer survivors, along with a physical activity tracker. They participated in individual consultations with a certified personal trainer, scheduled periodically during the first 6\u0026ndash;12 months of treatment. These sessions focused on developing and adapting a personalized exercise plan based on the participant\u0026rsquo;s fitness level, preferences, and any physical or logistical barriers to activity. Participants choosing yoga and mindfulness were enrolled in a six-week restorative yoga program designed to address fatigue, anxiety, depression, and other symptoms. The program emphasized mindfulness, resilience-building, and strengthening the mind\u0026ndash;body connection to support emotional and physical recovery. Those selecting massage therapy were referred to licensed massage therapists, with treatment techniques and frequency tailored to individual needs. Similarly, participants interested in acupuncture were referred to certified practitioners, and the number and frequency of sessions were personalized. Participants who did not choose any of the listed interventions but expressed interest in other complementary therapies were provided with educational resources relevant to their preferences.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHealth-related Quality of Life and Self-reported Cognitive Function\u003c/h3\u003e\n\u003cp\u003eParticipants completed validated surveys assessing menopausal symptoms, sexual function, general well-being, and cognitive function. QOL was measured using the Functional Assessment of Cancer Therapy, Breast Symptom Index (FACT-B, version 4) and the Functional Assessment of Cancer Therapy, Endocrine Symptoms (FACT-ES, version 4) (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). FACT-B includes items across six domains: physical well-being, social/family well-being, emotional well-being, functional well-being, relationship with the physician, and additional concerns, rated on a five-point Likert scale from 0 (not at all) to 4 (very much). FACT-ES includes 18 items focused on endocrine-related symptoms, particularly menopausal and sexual issues associated with breast cancer treatment. Self-reported cognitive function was assessed using the FACT\u0026ndash;Cognitive Function (version 3), a validated subjective tool designed to evaluate perceived cognitive decline among cancer patients. Patient-reported outcomes were assessed at baseline, 3 months, and every 6 months thereafter, for up to three years following enrollment.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive data were presented as mean (standard deviation) or median (range). Longitudinal changes in overall QOL and its domains were evaluated using linear mixed-effects models. Demographic and clinical variables, including ethnicity, age (\u0026lt;\u0026thinsp;35 vs. \u0026ge;35 years), body mass index, education level, marital status, and type of surgery, were analyzed for their association with QOL. Regression analyses were used to examine correlations between QOL, self-reported cognitive function, and other variables. All statistical analyses were conducted using linear mixed-effects modeling (SAS 9.4 (SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eForty premenopausal women were enrolled in the study between October 2018 and September 2019, with a median age of 43 years (range 26\u0026ndash;55). One patient was excluded from the QOL analysis after being found to have metastatic disease shortly after enrollment. The majority of participants were Caucasian (82%), with smaller proportions identifying as Indigenous, Black, or Asian (each 5% or less). Forty percent had a university degree, and over half were either married (53%) or in a common law relationship (7%). Most participants (73%) had children (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among the study participants, 30 (75%) received chemotherapy, including 20% who received neoadjuvant chemotherapy. Trastuzumab was administered to 8 patients (20%), one of whom had HER2-equivocal disease. A total of 80% of patients had T2 or node-positive disease, and 18% were HER2-positive. Thirty-six patients (90%) underwent adjuvant radiation therapy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Demographic Characteristics of Study Participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaucasian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndigenous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity degree\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelationship\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommon law relationship\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChildren\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and Treatment Characteristics of Study Participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;40 (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 years (range: 26\u0026ndash;55 years)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbid illness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 mm (10\u0026ndash;86 mm)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLumpectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral mastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceived chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant trastuzumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant endocrine therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExemestane plus ovarian suppression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastrozole plus ovarian suppresion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLetrozole plus goserelin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTamoxifen plus goserelin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e* 36 women received goserelin\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong patients with T1N0 HR+/HER2-negative disease, all had high or intermediate Oncotype DX recurrence scores. Twenty-two patients (55%) received a combination of anthracycline- and taxane-based chemotherapy regimens, including dose-dense AC followed by paclitaxel, or FEC-100 followed by docetaxel or paclitaxel. An additional 8 patients (20%) received 4 to 6 cycles of adjuvant docetaxel and cyclophosphamide.\u003c/p\u003e \u003cp\u003eEndocrine therapy consisted of exemestane in 40% of patients, anastrozole in 32%, letrozole in 23%, and tamoxifen in 5%, all combined with ovarian suppression. Thirty-six patients (90%) received goserelin, a gonadotropin-releasing hormone (GnRH) analog, while 4 (10%) underwent upfront oophorectomy. An additional 21 patients (53%) later underwent bilateral oophorectomy, bringing the total number of women who ultimately received surgical ovarian suppression to 25 (63%)\u003c/p\u003e \u003cp\u003eAcross the cohort, exercise-based strategies were the most frequently selected intervention, with approximately 61% of participants choosing some form of physical activity, ranging from mild to strenuous exercise with an exercise trainer. Massage therapy represented the second most common choice, selected by 44% of participants, followed by acupuncture, which was used by 35% of women. Overall, about 65% of participants opted for a single supportive intervention, whereas 35% engaged in combinations involving more than one intervention with approximately 9% utilizing more than two interventions.\u003c/p\u003e \u003cp\u003eResults from the linear mixed-effects model indicated a statistically significant improvement in functional well-being, which increased by 1.65 points per year (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), reflecting better day-to-day functioning (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Emotional well-being showed a non-significant improvement, with a decrease of 0.26 points per year (p\u0026thinsp;=\u0026thinsp;0.14), suggesting reduced emotional distress over time (Figure IB; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Social/family well-being showed a non-significant increase of 0.34 points per year (p\u0026thinsp;=\u0026thinsp;0.18). The total FACT-ES score, where higher scores indicate greater endocrine-related symptom burden, decreased by 0.72 points per year, suggesting a potential reduction in symptoms; however, this change was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.18) [Figure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003eB]. Physical well-being and perceived cognitive abilities remained stable, with no significant changes observed over time (p\u0026thinsp;=\u0026thinsp;0.96 and p\u0026thinsp;=\u0026thinsp;0.61, respectively). Over a 60-month follow-up period, 92.5% of patients remained adherent to adjuvant endocrine therapy. Four participants (10%) experienced disease recurrence, and two (5%) died during follow-up. Taken together, these findings indicate that individualized interventions may help mitigate declines in quality of life and cognitive function during endocrine therapy and may support continued treatment adherence.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLinear mixed-effects (LME) model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEstimate (standard error)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal FACT-ES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.20 (0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Functional Well-Being\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.65 (0.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.0005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Emotional Well-being\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.26 (0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Social/Family Well-Being\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.13 (0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Physical Well-Being\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.53 (0.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerceived Cognitive Abilities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eDuring the study period, functional well-being significantly improved by 1.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43 points per year (p\u0026thinsp;=\u0026thinsp;0.0005). Emotional well-being improved by 0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 points per year (p\u0026thinsp;=\u0026thinsp;0.14). Total FACT-ES (\u0026ndash;0.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54; p\u0026thinsp;=\u0026thinsp;0.71), social/family well-being (0.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39; p\u0026thinsp;=\u0026thinsp;0.74), physical well-being (-0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40; p\u0026thinsp;=\u0026thinsp;0.19), and perceived cognitive abilities (0.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65; p\u0026thinsp;=\u0026thinsp;0.86) remained stable over time\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the multivariable analysis, younger age (\u0026lt;\u0026thinsp;35 years) was consistently associated with poorer outcomes across several domains. Younger women reported higher FACT-ES total scores (Estimate\u0026thinsp;=\u0026thinsp;8.76, SE\u0026thinsp;=\u0026thinsp;3.89, p\u0026thinsp;=\u0026thinsp;0.02), greater perceived cognitive impairment (Estimate\u0026thinsp;=\u0026thinsp;13.76, SE\u0026thinsp;=\u0026thinsp;7.16, p\u0026thinsp;=\u0026thinsp;0.05), more negative comments from others (Estimate\u0026thinsp;=\u0026thinsp;5.01, SE\u0026thinsp;=\u0026thinsp;0.81, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and a greater overall impact on quality of life (Estimate\u0026thinsp;=\u0026thinsp;4.99, SE\u0026thinsp;=\u0026thinsp;1.56, p\u0026thinsp;=\u0026thinsp;0.001). Participants identifying as Caucasian reported lower functional well-being (Estimate = \u0026minus;\u0026thinsp;3.39, SE\u0026thinsp;=\u0026thinsp;1.71, p\u0026thinsp;=\u0026thinsp;0.05) and lower perceived cognitive abilities (Estimate = \u0026minus;\u0026thinsp;7.90, SE\u0026thinsp;=\u0026thinsp;2.66, p\u0026thinsp;=\u0026thinsp;0.003) compared with other racial groups. Marital status demonstrated a protective association in one domain, with married participants reporting fewer negative comments from others (Estimate = \u0026minus;\u0026thinsp;1.89, SE\u0026thinsp;=\u0026thinsp;0.69, p\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003ePremenopausal women undergoing combination endocrine therapy often experience substantial treatment-related challenges that can negatively affect quality of life, cognitive function, and long-term adherence (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The MyChoice study was designed to address this need by offering a flexible, patient-centered model in which women selected individualized behavioral and complementary interventions tailored to their symptoms, preferences, and readiness for engagement. This approach aimed to support self-management, promote resilience, and ultimately maintain treatment tolerance and adherence throughout the course of adjuvant endocrine therapy.\u003c/p\u003e \u003cp\u003eThe findings from this study provide encouraging evidence that individualized supportive interventions can help preserve, and even enhance, several aspects of well-being during intensive endocrine therapy. Functional well-being improved significantly over time, suggesting that targeted exercise guidance and structured activity planning may have contributed to enhanced energy, daily functioning, and overall physical capability (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Emotional well-being also improved, consistent with benefits previously reported from mindfulness-based practices, yoga, and other mind\u0026ndash;body interventions that help women cope with stress, anxiety, and the emotional burden of treatment. Social and endocrine symptom domains showed favorable, though not statistically significant, trends toward improvement. Importantly, physical well-being and cognitive abilities remained stable, which is notable given that declines are commonly observed in premenopausal women receiving aromatase inhibitors with ovarian suppression (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The maintenance of these domains indicates that supportive interventions may mitigate the typical deterioration expected from endocrine therapy alone.\u003c/p\u003e \u003cp\u003eAdherence outcomes in this cohort were particularly noteworthy. Over a follow-up period of 60 months, more than 90% of participants remained adherent to endocrine therapy, a rate that exceeds adherence reported in many other studies. This high level of persistence suggests that individualized supportive care may play an important role in sustaining engagement with treatment, ultimately enhancing long-term disease control.\u003c/p\u003e \u003cp\u003eMultivariable analyses identified several patient characteristics that appeared to be associated with quality-of-life outcomes. Younger women reported greater symptom burden and more cognitive concerns, consistent with prior evidence that this subgroup may face increased challenges during endocrine therapy. These observations reinforce the importance of considering tailored supportive strategies that address the specific needs of younger patients. Exploratory differences by race and marital status further suggest that women\u0026rsquo;s experiences throughout treatment may be influenced not only by clinical factors but also by their broader social and cultural environments. The tendency for married participants to report fewer negative comments from others may reflect stronger partner-based social support, which has been shown to positively influence coping and psychosocial adjustment in women with breast cancer (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Although based on a modest sample size, the gradual improvement observed in functional well-being over time suggests a potential cumulative benefit of continued engagement in supportive interventions.\u003c/p\u003e \u003cp\u003eA major strength of the MyChoice study is its individualized, adaptive intervention model, which allowed participants to select therapies aligned with their needs, preferences, and side-effect profiles. This patient-centered approach likely enhanced acceptability and engagement by empowering participants and promoting self-management. Such flexibility mirrors real-world clinical practice more closely than structured, uniform intervention protocols and highlights a feasible pathway for integrating complementary support into routine oncology care.\u003c/p\u003e \u003cp\u003eThe study also has limitations that should be acknowledged. The absence of a control group limits definitive conclusions about causality, and the modest sample size may reduce the power to detect smaller but meaningful changes in some quality-of-life domains. Variation in participants\u0026rsquo; uptake and adherence to supportive therapies may also have influenced outcomes in ways not fully captured in the analyses. Nonetheless, these limitations are consistent with a phase II exploratory design, and the findings provide a strong foundation for future controlled trials.\u003c/p\u003e \u003cp\u003eOverall, the MyChoice study demonstrates that individualized behavioral and complementary interventions may help maintain or improve key aspects of quality of life in premenopausal women receiving combination endocrine therapy. The improvements observed in functional and emotional well-being, coupled with the stability of physical and cognitive outcomes and the high rate of treatment adherence, support the value of integrating personalized supportive care into standard breast cancer management. These promising results justify further evaluation in a larger, randomized trial to more definitively assess the impact of tailored, patient-driven supportive interventions on survivorship outcomes.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn conclusion, the integration of personalized supportive care into standard oncology practice represents a promising avenue to optimize survivorship in young breast cancer patients. MyChoice highlights that empowerment through choice, coupled with holistic support, can lead to measurable improvements in quality of life making the cancer journey more tolerable and potentially more successful.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFUND\u003c/h2\u003e\n\u003cp\u003eThis work was funded by a research grant from the College of Medicine, University of Saskatchewan (CMRAD 419711).\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eS.A. (Shahid Ahmed) conceived and designed the study, secured funding, supervised the project, and critically revised the manuscript. S.M. (Sonya Mannala) and W.M. contributed to data collection, study coordination, and manuscript preparation. P.M. performed statistical analyses and contributed to data interpretation. L.D., D.G.L., S.K., A.C., and A.L. contributed to study methodology, implementation of supportive interventions, and interpretation of results. N.I., M.S., M.I.K., O.A., M.M., A.B., K.H., H.I.C., and A.S. (Amer Sami) contributed to patient recruitment, clinical data acquisition, and manuscript review.All authors reviewed, edited, and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors express their sincere gratitude to all the patients who participated in the MyChoice study for their willingness to share their experiences and for their invaluable contributions. We also thank the Saskatchewan Breast Cancer Tumor Group whose engagement and advocacy helped facilitate study awareness and patient involvement. The Saskatchewan Cancer Agency provided essential clinical and administrative support, including the dedicated efforts of its Clinical Trials Unit. We further extend our appreciation to the College of Medicine at the University of Saskatchewan for providing funding and support of this research.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are stored in the institutional electronic data capture platform REDCap hosted at the University of Saskatchewan. Due to ethical and privacy restrictions, the data are not publicly available. Access to the data may be granted upon reasonable request and with appropriate approval from the University of Saskatchewan Research Ethics Board (USASK REB) and the Saskatchewan Cancer Agency, in accordance with institutional policies and data governance regulations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSiegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49.\u003c/li\u003e\n \u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.\u003c/li\u003e\n \u003cli\u003eKim J, Harper A, McCormack V, Sung H, Houssami N, Morgan E, Mutebi M, Garvey G, Soerjomataram I, Fidler-Benaoudia MM. Global patterns and trends in breast cancer incidence and mortality across 185 countries. 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Effects of yoga on improving quality of life in patients with breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer. 2021 Mar;28(2):264-276.\u003c/li\u003e\n \u003cli\u003eLesi G, Razzini G, Musti MA,\u0026nbsp;et al. Acupuncture As an Integrative Approach for the Treatment of Hot Flashes in Women With Breast Cancer: A Prospective Multicenter Randomized Controlled Trial (AcCliMaT) J Clin Oncol.\u0026nbsp;2016;34:1795-802\u003c/li\u003e\n \u003cli\u003eZhang Y, Sun Y, Li D, Liu X, Fang C, Yang C, Luo T, Lu H, Li H, Zhang H, Liang Q, Wu J, Huang L, Xu R, Ren L, Chen Q. Acupuncture for Breast Cancer: A Systematic Review and Meta-Analysis of Patient-Reported Outcomes. Front Oncol. 2021 Jun 10;11:646315.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMcCorkle R, Ercolano E, Wagner E. Self-management. Enabling and empowering patients living with cancer as a chronic illness. CA Cancer J Clin. 2011;61:50-62.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eT Cella D, Tulsky D, Gray G, et al. The Functional Assessment of Cancer Therapy scale: Development and validation of the general measure. J Clin Oncol 1993;11:570-79.\u003c/li\u003e\n \u003cli\u003eKroenke CH, Kubzansky LD, Schernhammer ES, Holmes MD, Kawachi I. Social networks, social support, and survival after breast cancer diagnosis. J Clin Oncol. 2006 Mar 1;24(7):1105-11.\u003c/li\u003e\n \u003cli\u003eBelau MH, Jung L, Maurer T, Obi N, Behrens S, Seibold P, Becher H, Chang-Claude J. Social relationships and their impact on health-related quality of life in a long-term breast cancer survivor cohort. Cancer. 2024 Sep 15;130(18):3210-3218. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Premenopausal breast cancer, endocrine therapy adherence, quality of life, supportive care, complementary interventions","lastPublishedDoi":"10.21203/rs.3.rs-8935918/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8935918/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePremenopausal women receiving combination endocrine therapy often experience substantial declines in quality of life (QOL), cognitive functioning, and treatment adherence. The MyChoice study evaluated whether individualized behavioral and complementary interventions could help maintain or improve QOL and treatment adherence in women with early-stage hormone receptor\u0026ndash;positive breast cancer undergoing aromatase inhibitor- or tamoxifen-based therapy with ovarian suppression.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e MyChoice was a prospective multicenter phase II study in which participants selected tailored supportive interventions, including structured exercise programs, restorative yoga, acupuncture, and massage therapy. QOL and cognitive function were assessed at baseline, 3 months, and every 6 months for up to 3 years using FACT-B, FACT-ES, and FACT\u0026ndash;Cognitive Function instruments. Longitudinal changes were analyzed using linear mixed-effects models. Other outcomes included treatment adherence and demographic or clinical predictors of QOL.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eForty premenopausal women participated, with a median age of 43 years. Exercise was the most frequently selected intervention (61%), followed by massage therapy (44%) and acupuncture (35%). Functional well-being improved significantly over time (1.42 points/year, p\u0026thinsp;=\u0026thinsp;0.01). Emotional well-being, social/family well-being, physical well-being, endocrine symptoms, and perceived cognitive abilities remained stable. Adherence to endocrine therapy was high at 92.5% over follow-up period. In multivariable models, younger age (\u0026lt;\u0026thinsp;35 years) was associated with higher symptom burden across several domains, while functional well-being improved steadily with time.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIndividualized, patient-selected supportive interventions may help maintain or improve key aspects of QOL, stabilize cognitive function, and support high adherence to endocrine therapy in premenopausal women with early-stage breast cancer. These findings support further evaluation in larger controlled trials.\u003c/p\u003e","manuscriptTitle":"Role of Individualized Intervention(s) on Quality of Life and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer: MyCHOICE Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-17 13:36:26","doi":"10.21203/rs.3.rs-8935918/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c1d60344-627f-4a93-b350-826a7e4b2045","owner":[],"postedDate":"March 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T17:10:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-17 13:36:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8935918","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8935918","identity":"rs-8935918","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}