BACKGROUND: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET).
METHODS: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials.
RESULTS: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases.
CONCLUSIONS: AI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.

UNASSIGNED: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model.
UNASSIGNED: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test.
UNASSIGNED: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test (χ2 = 26.36; p = 0.999).
UNASSIGNED: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.

OBJECTIVE: Longitudinal patient tolerability data collected as part of randomized controlled trials are often summarized in a way that loses information and does not capture the treatment experience. To address this, we developed an interactive web application to empower clinicians and researchers to explore and visualize patient tolerability data.
METHODS: We used adverse event (AE) data (Common Terminology Criteria for Adverse Events) and patient-reported outcomes (PROs) from the NSABP-B35 phase III clinical trial, which compared anastrozole with tamoxifen for breast cancer-free survival, to demonstrate the tools. An interactive web application was developed using R and the Shiny web application framework that generates Sankey diagrams to visualize AEs and PROs using four tools: AE Explorer, PRO Explorer, Cohort Explorer, and Custom Explorer.
RESULTS: To illustrate how users can use the interactive tool, examples for each of the four applications are presented using data from the NSABP-B35 phase III trial and the NSABP-B30 trial for the Custom Explorer. In the AE and PRO explorers, users can select AEs or PROs to visualize within specified time periods and compare across treatments. In the cohort explorer, users can select a subset of patients with a specific symptom, severity, and treatment received to visualize the trajectory over time within a specified time interval. With the custom explorer, users can upload and visualize structured longitudinal toxicity and tolerability data.
CONCLUSIONS: We have created an interactive web application and tool for clinicians and researchers to explore and visualize clinical trial tolerability data. This adaptable tool can be extended for other clinical trial data visualization and incorporated into future patient-clinician interactions regarding treatment decisions.

BACKGROUND: Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients.
METHODS: Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done.
RESULTS: After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM.  Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

BACKGROUND: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271).
METHODS: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening), or 24:00-05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here.
RESULTS: ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53-1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22-0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68-1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16-0.91]).
CONCLUSIONS: Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies.
BACKGROUND: UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.

OBJECTIVE: Adjuvant endocrine therapy (AET) reduces recurrence risk after hormone receptor-positive breast cancer, but non-adherence is common. We pilot-tested SOIE, a program to enhance AET experience and adherence, to assess its acceptability, feasibility, and effects on psychosocial precursors of AET adherence.
METHODS: We conducted a 12-month pilot randomized controlled trial among women who had a first AET prescription. Intervention group received SOIE while control group received usual care. Psychosocial factors from the Theory of Planned Behavior (TPB) (intention - primary outcome -, attitude, subjective norm, behavioral control), additional constructs (AET knowledge, social support, coping planning), impact of AET services received, and adherence were measured by questionnaires at baseline, 3-month, and 12-month endpoints. Group patterns were compared using repeated measures analyses with generalized estimating equations.
RESULTS: A total of 106 women were randomized (participation = 54.9%; intervention n = 52; control n = 54; retention = 93.8%). Among SOIE women, ≥ 90% received the program components and were satisfied. Both groups scored high on adherence intentions and group patterns over time were not statistically different. In the intervention group, AET knowledge and coping planning with side effects increased (group-by-time p-value = .002 and .016), a higher proportion reported that AET services received helped them take their AET (p < .05) and have a consistent daily intake (p = .01).
CONCLUSIONS: SOIE is feasible and acceptable for survivors with an AET. SOIE did not significantly impact adherence intentions but was beneficial for other program outcomes and daily intake.
CONCLUSIONS: SOIE may represent an encouraging avenue to enhance supportive care and empower survivors with managing AET.

(1) Background/Objectives: To investigate the nationwide screening practices and trends in tamoxifen retinal toxicity (tamoxifen retinopathy) in South Korea using national health insurance claims data. (2) Methods: A total of 43,848 patients who started tamoxifen therapy between 2015 and 2020 and had no prior ophthalmic diseases or other conditions requiring screening for retinopathy were included. The annual numbers of tamoxifen users and new initiators of tamoxifen therapy were assessed. The screening examinations were separated into baseline (first ophthalmic examination after tamoxifen administration) and subsequent monitoring examinations. The timing and modalities for the baseline and subsequent monitoring examinations performed between 2015 and 2021 were assessed in tamoxifen users. (3) Results: The annual number of tamoxifen users increased over the study period from 54,056 in 2015 to 81,720 in 2021. The number of patients who underwent ophthalmic examination after tamoxifen administration was 8961 (20.4%). Baseline screening was performed in 6.5% of patients within 1 year of use, and subsequent monitoring was performed in 27.8% of patients who underwent baseline screening. Funduscopy or fundus photography was performed most commonly for baseline screening and subsequent monitoring (99.0% and 98.6%, respectively), while optical coherence tomography was performed only in 21.9% and 29.6% of baseline and monitoring examinations, respectively. The average number of monitoring examinations per year was 0.68 ± 0.45. Although the annual percentage of patients receiving a baseline examination within 1 year gradually increased over time, the percentage of those with subsequent monitoring performed within 1 year was similar over the study period. (4) Conclusions: Our finding, appropriate screening in a small proportion of patients receiving tamoxifen, suggests the need to promote awareness among healthcare professionals and develop a standardized approach for screening for tamoxifen retinopathy.

UNASSIGNED: Tamoxifen is a drug that has been used extensively as a chemotherapeutic agent for breast cancer. It should be taken for a long period, from few weeks up to many years, so it can induce gynecological and nongynecological complications.
UNASSIGNED: Present study was conducted to clarify the histopathological effects of tamoxifen intake on the ovarian follicles of rats and evaluate the promising recovery after drug withdrawal.
UNASSIGNED: Adult female albino rats (n = 24) were randomly divided into four groups. Group I: Control rats without treatment. Group II: Rats received olive oil vehicle. Group III: Rats received 5 mg/kg daily of tamoxifen dissolved in olive oil by oral administration for 4 weeks. Group IV: Rats received tamoxifen as in Group III then will be kept for another 4 weeks without treatment for recovery. Then, the rats were anaesthetized and the ovaries were removed and prepared for histological assessment by light microscope.
UNASSIGNED: The ovarian histological findings in the ovary of Group III revealed an increase in atretic ovarian follicles, appearance of cystic ovarian follicles, and cystic corpus luteum. The granulosa cells of ovarian follicles were disorganized with vacuolation of their cytoplasm, increased number of pyknotic nuclei, fragmented nuclei, and apoptotic bodies. After the withdrawal of drug, the ovarian tissue showed slight improvement with the appearance of some atretic follicles with degenerated oocyte and stromal hyperplasia.
UNASSIGNED: Based on the results, tamoxifen induced marked histological changes in the ovary. If tamoxifen is mandatory for the prevention of breast cancer, frequent gynecological examination should be carried out to detect any side effects.

Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer\'s development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN\'s pivotal role in tamoxifen resistance. Furthermore, the Kruskal-Wallis rank test indicated UTRN\'s potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN\'s close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN\'s role in breast cancer\'s prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.