BACKGROUND:Predictions of Health-Related Quality of Life (HRQoL) outcomes could support realistic recovery expectations after breast cancer (BC) surgery. We aimed to develop and validate prediction models for HRQoL outcomes after BC surgery. METHODS:We used three datasets of BC patients from Berlin, Germany; Ljubljana, Slovenia; and Rotterdam; Netherlands. We included non-metastasised patients who were surgically treated for an initial diagnosis of BC and completed pre- and postoperative validated questionnaires. We used linear mixed models to analyse 15 domains of the EORTC QLQ-C30 and EORTC QLQ-BR23 over a two-year horizon. Baseline domain score (measured pre-operatively), age, BMI, smoking, TN stage, receptor status, neoadjuvant chemotherapy, axillary surgery and surgery type (breast-conserving, mastectomy, and immediate implant-based reconstruction) were included as predictors. Predictive performance at validation was assessed by the proportion of variance explained (marginal R2; mR2). RESULTS:We included N = 795 patients from Germany for development and N = 623 from Slovenia and N = 417 from Netherlands for validation. The largest proportion of variance was explained by the prediction models for sexual functioning (SF, mR2 35%), physical functioning (PF, mR2 29%), body image (BI, mR2 26%), and cognitive functioning (CF, mR2 25%). The models captured meaningfully different trends over time for different outcomes and surgery types. The predictive performance of the models was largely driven by the baseline domain score. Performance was reasonable at external validation, with r2 values of 19-33% for PF, 10-17% for CF, 15-18% for BI, and 22-28% for SF, although some other outcomes (e.g. breast symptoms and role functioning) showed miscalibration, indicating a need for recalibration. CONCLUSION:HRQoL after breast cancer surgery can be predicted using simple models with baseline domain scores and surgery type, demonstrating a new opportunity for Patient-Reported Outcome Measures (PROMs) in personalized care.

BACKGROUND:In patients with hormone receptor (HR)-positive early breast cancer (BC), the POSITIVE trial demonstrated that temporary interruption of adjuvant endocrine therapy (ET) for pregnancy is feasible and safe in early follow-up (median 41 months). In this article, we report updated results from a preplanned analysis with 2.5 years of additional follow-up. PATIENTS AND METHODS:POSITIVE, a single-arm prospective trial evaluating temporary interruption of adjuvant ET (after 18-30 months and for up to 2 years) to attempt pregnancy in young patients with BC, enrolled 518 eligible women (≤42 years of age, stage I-III BC, desiring pregnancy) from December 2014 to December 2019. Using the bootstrap-matching method, 5-year breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) event rates were compared with those of the SOFT/TEXT trials as external controls. RESULTS:At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT cohort, the 5-year cumulative incidence of BCFI events was 12.3% in POSITIVE and 13.2% in SOFT/TEXT [-0.9% difference, 95% confidence interval (CI) -4.2% to 2.6%]. The 5-year cumulative incidence of DRFI events was 6.2% and 8.3%, respectively (-2.1% difference, 95% CI -4.5% to 0.4%). Among 497 women followed for nondisease outcomes, 377 (76%) had ≥1 documented pregnancy on trial, and 343 of 497 (69%) had ≥1 live birth, totaling 440 offspring. In an unadjusted analysis comparing the 180 women (36%) who had pre-enrollment embryo/oocyte cryopreservation with those who did not, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI 9.6% to 20.2%) and 11.5% (95% CI 8.4% to 15.7%), respectively. CONCLUSION:Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy, including use of fertility preservation, does not increase the risk of BC events. Continued follow-up is warranted given the known risk of late recurrence in this population.

e12701 Background: Integrated rehabilitation improves quality of life in breast cancer patients, but its impact on long-term outcome of disease is unclear. The aim of our study was to find out whether early initiation of integrated rehabilitation is associated with a lower incidence of distant metastases. Methods: The subjects of our prospective study were 553 female non-metastatic invasive breast cancer patients (26-65 (mean 52) years of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients in 2019-2022. The patients completed three questionnaires (EORTC QLQ - C30, B23 and NCCN): before, six and twelve months after the beginning of cancer treatment. The control group included 278 patients and the intervention group 275 patients. The control group obtained the same rehabilitation as was offered to all breast cancer patients in our hospital before the start of our study. The multidisciplinary rehabilitation team reviewed the documentation of all the patients from the intervention group before, six and twelve months after the beginning of treatment and recommended appropriate interventions according to the patient's problems. The integrated rehabilitation coordinator referred patients for additional treatments in compliance with the institute’s new clinical pathway (psychologist, general practitioner, nutritional treatment, physical rehabilitation, kinesiologist-guided online exercises, gynaecologist, analgesia, vocational rehabilitation). Data on the patients’ demographics, disease extent, cancer treatment, distant dissemination and distant disease-free survival were collected. This data were analysed using the chi-square and ANOVA test. Distant disease-free survival and disease-specific survival were estimated using the Kaplan–Meier method, and between-group differences were assessed using the Cox proportional hazards model. Adjustment for tumor subtype and type of systemic therapy was not performed. Results: There were no differences between the control and the intervention group of patients in terms of age, education, disease extent, surgical procedures, systemic cancer treatment, radiotherapy, or disease-specific survival. The follow-up period ranged from 1 to 72 (median 57) months. Distant metastases occurred in 3% of the intervention group and 7% of the control group. Distant disease-free survival was 97% in the intervention group and 94% in the control group (HR = 0.43, 95% CI 0.19-0.98; p = 0.04). Conclusions: Early integrated rehabilitation is associated with longer distant disease-free survival compared to the control group. These findings suggests that early individualised integrated rehabilitation may contribute not only to improved quality of life but also to favourable long-term oncological outcomes.

PREDICT Breast is an online tool that provides survival predictions for patients with early-stage breast cancer, for different treatments after surgery. External validation is essential to assess model performance across populations and healthcare settings. We aimed to externally validate PREDICT using clinical practice data from the Netherlands, Sweden, and Slovenia. We validated PREDICT in national populations (Netherlands, N = 221,636; Sweden, N = 84,928) and in two specific subgroups: patients with invasive lobular breast cancer (ILC) (Netherlands, N = 26,834; Sweden, N = 10,563; Slovenia, N = 341) and patients aged ≤ 40 years (Netherlands, N = 9995; Sweden, N = 2694). We assessed discrimination with the 10-year area under the curve (AUC) and calibration of 10-year mortality predictions through calibration plots, intercepts and slopes. PREDICT v3.1 discriminated well in the national populations (Netherlands AUC 0.75, 95

Background: The treatment landscape in HR+/HER2− metastatic breast cancer (mBC) is continuously evolving, with evidence on new agents and combinations published almost every year. Despite updated therapeutic guidelines, second-line (2L) selection may be challenging due to clinical factors, biomarker status, and available agents. Methods: A two-round Delphi consensus was organized in July 2024, gathering input from 10 experts in research, diagnosis, and treatment of HR+/HER2− mBC on optimal 2L and beyond choice, considering the available biomarkers and results from published clinical trials. Consensus was defined as 70% agreement or disagreement. Results: The experts considered initially a list of 39 statements, structured into the following four sections: biomarker testing; selection of 2L treatment at progression of disease on first line endocrine therapy (ET) + CDK4/6i at ≥6 months after initiation of ET for mBC; selection of 2L treatment at disease progression on ET + CDK4/6i, at <6 months after initiation of ET for mBC, whilst on ET; and selection of post-2L treatment options. After a discussion, the experts decided to remove four statements, refine ten, and include three new ones. The final list consisted of 38 statements, and consensus was achieved in 37. Conclusions: The panel recommends next-generation sequencing as the method of choice for genomic characterization at disease progression on first line. The optimal agent or treatment class is indicated depending on the presence of specific mutations; however, the panel admits that the strategy is different in clinical practice, where novel therapies might not be available or reimbursed.

Systemic therapy has been shown to improve survival in many cancer patients. The number of anticancer drugs has increased dramatically in recent decades and more than half of all cancer patients are treated with these drugs. The specificity of the disease, the specificity of the treatment, and the drugs, which often have a very narrow therapeutic window, have necessitated the development of a new specialty, medical oncology, separate from internal medicine. Since 2000, medical oncology has been recognized in Slovenia as an independent specialization separate from internal medicine. The incidence of cancer in Slovenia is increasing, and there are more and more patients who need systemic treatment and management by medical oncologists. Unfortunately, the number of oncologists is not increasing at the same rate as the number of patients, and the existing facilities are becoming inadequate.

Purpose: The POSITIVE trial showed that premenopausal women with breast cancer (BC) can safely pause adjuvant endocrine treatment (ET) to attempt conception. 74 % of patients conceived spontaneously or through assisted reproductive technology (ART); Investigating hormonal factors that predict fertility was a key secondary endpoint. Methods: Hormonal factors were assessed in non-pregnant women at months 3, 6, and 12 after ET interruption. The frequency of low ovarian reserve, defined as anti-Mullerian hormone (AMH) < 0.5 ng/mL at month 3, and of premature ovarian insufficiency (POI), defined as follicle stimulating hormone (FSH) > 25 IU/L at month 12, were primary measures. Secondary analyses to predict pregnancy included AMH, FSH, thyroid stimulating hormone (TSH), prolactin and ovulatory status (defined as progesterone >3 ng/mL at month 6), considering covariates such as age, treatment, and ART use. Results: Of 518 women enrolled in POSITIVE, 438 were eligible for low ovarian reserve analysis. Low ovarian reserve was observed in 209 women (47.7 %), more frequently among older women and those with prior chemotherapy, but not in relation to ET type or duration. Overall, low ovarian reserve was associated with reduced odds of pregnancy (OR:0.52; 95 % CI:0.31–0.87). Of 142 patients evaluated for POI, 16.7 % of those who received prior chemotherapy experienced POI. FSH at month 3 was associated with POI, but only modestly with spontaneous pregnancy (OR:0.96; 95 %CI: 0.93–1.00); other factors were not predictive of pregnancy. Conclusion: Hormonal factors are associated with pregnancy in BC patients pausing adjuvant ET to conceive, and their assessment may help to optimize fertility counseling. Trial registration: ClinicalTrials.gov number NCT02308085.

PURPOSE:We investigated breastfeeding patterns, behaviors, and association with breast cancer (BC) outcomes in women with early hormone receptor-positive (HR+) BC who had a live birth in the POSITIVE trial. PATIENTS AND METHODS:POSITIVE is a prospective trial that demonstrated no increased short-term risk of BC events in women with early HR+ BC who interrupted endocrine therapy (ET) to attempt pregnancy. We describe the frequency, duration, and laterality of breastfeeding and estimate the cumulative incidence of BC events by breastfeeding status. RESULTS:At a median follow-up of 41 months, 317 patients had at least one live birth and 313 were eligible for this analysis. A total of 196 of 313 (62.6%) patients breastfed. A total of 130 of the 167 women (77.8%) who had breast-conserving surgery breastfed, and 90 of 130 (69.2%) breastfed from the unaffected breast only. Sixty-six of the 146 women (45.2%) who underwent unilateral mastectomy breastfed. The frequency of breastfeeding was higher in women older than 35 years (67.6% v 55.7%) and in those without previous children (66.4% v 48.5%). Over half (103 of 196, 52.6%) of women breastfed their first live birth for >4 months (median 4.4 months; 95% CI, 4.0 to 5.3). The cumulative incidence of a BC event at 24 months from first on-study live birth was 3.6% and 3.1% in the breastfeeding and nonbreastfeeding groups, respectively (0.5% difference; 95% CI, -4.3% to 5.2%). CONCLUSION:In POSITIVE, two thirds of women who gave birth after BC diagnosis breastfed, mostly for 4 months or more. In early follow-up, we did not observe differences in BC-related events in women who breastfed compared with those who did not. These results are key for women who wish to pursue pregnancy and breastfeeding after BC.

e12650 Background: Results from the Keynote 522 clinical trial, which played a pivotal role in evaluating the efficacy of neoadjuvant pembrolizumab in combination with chemotherapy (NAICT), showed a significant improvement in pathological complete response (pCR) rates compared with chemotherapy alone. To date, no significant markers have been identified to predict pathological complete response to NAICT. The primary objective was to identify markers, both molecular and clinical, predictive of pCR to NAICT in a real-world clinical setting. Methods: The retrospective analysis included 38 consecutively treated pts with early stage TNBC who received NAICT including pembrolizumab at the Institute of Oncology, Ljubljana (OIL) between 4 January 2022 and 17 October 2023. Data collected from electronic medical records included tumour size, nodal status, UICC stage, BRCA status, systemic immune-inflammation index (SII) before NAICT and before surgery, and frequency and grade of immune-related adverse events (iAEs) (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5). In pts who completed surgical treatment, response to treatment was assessed by pathological examination of post-treatment surgical specimens. Descriptive statistical methods were used to summarise and describe the main characteristics. Pearson chi-squared test was used to analyse categorical variables and t-test to evaluate associations between continuous variables. Results: Of the 38 pts, 28 completed surgical treatment and were further analysed. Pathohistological examination of post-treatment surgical specimens revealed pCR in 11 pts (39.3%), with residual disease in 17 pts (60.7%). Of the 17 pts without pCR, 11 pts had RCB score 2 (64.7%) and 5 pts had score 3 (29.4%). The distribution of size, nodal status, UICC stage at diagnosis, BRCA status, frequency of iAEs in correlation with pCR is shown in the Table. A borderline correlation was found between pCR and SII at the start of pembrolizumab treatment (p=0.05). Age, tumour size, nodal status, UICC stage, BRCA status, AEs, SII before surgery were not found to be predictive of pCR. Conclusions: SII at the start of pembrolizumab was found to be a borderline significant marker predictive of pCR. Other characteristics evaluated did not correlate with pCR. [Table: see text]

11007 Background: Return to work is beneficial both for breast cancer (BC) patients and for society. This study explored the impact of early integrated and vocational rehabilitation on sick leave and disability one year after the start of cancer treatment in BC patients. Methods: The subjects of our prospective study were 435 employed female BC patients (26-65 (mean 52) years of age), who participated in the pilot study on the individualized integrated rehabilitation in 2019-2022 and were followed for at least one year. There were 211 patients in the control group and 224 in the intervention group. The patients completed three questionnaires (EORTC QLQ - C30, B23, and NCCN): before, half and one year after the start of cancer treatment. The control group received the standard rehabilitation programme, offered to all BC patients before the start of the study. The multidisciplinary rehabilitation team reviewed the documentation of the patients from the intervention group before, half and one year after the start of treatment and recommended appropriate interventions according to the patient's needs in compliance with the institute’s new clinical pathway (psychologist, general practitioner, nutritional treatment, physical rehabilitation, kinesiologist-guided online exercises, gynaecologist, analgesia, vocational rehabilitation). Data on the patients’ demographics and needs reported in questionnaires, the extent of the disease and cancer treatment were collected. These data and the frequency of sick leave and disability retirement one year after the start of treatment in both groups of patients were analysed using the chi-square and ANOVA test. Results: The patients from the intervention group had 50 calendar days shorter sick leave compared to the control group (p = 0.002). Patients without metastatic disease from the intervention group had 52 calendar days shorter sick leave compared to the control group (p = 0.002). The intervention group treated with chemotherapy had 43 calendar days shorter sick leave compared to the control group (p = 0.029). The difference in sick leave of the group of patients who did not receive chemotherapy was statistically borderline significant (50 calendar days, p = 0.053). The patients in the intervention group had a better work ability (p < 0.001) and less disability (p < 0.001) than the patients in the control group one year after the start of treatment. Conclusions: One year after the beginning of cancer treatment, patients from the intervention group had shorter sick leave, better work ability, and a lower proportion of disability compared to the control group.

Background Recent evidence brought by novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates is leading to significant changes in HER2-negative breast cancer (BC) best practices. A new targetable category termed ‘HER2-low’ has been identified in tumors previously classified as ‘HER2-negative’. Daily practice in pathology and medical oncology is expected to align to current recommendations, but patient access to novel anticancer drugs across geographies might be impeded due to local challenges. Materials and methods An expert meeting involving ten regional pathology and oncology opinion leaders experienced in BC management in four Central and Eastern Europe (CEE) countries (Bulgaria, Croatia, Serbia, Slovenia) was held. Herein we summarized the current situation of HER2-low metastatic BC (mBC), local challenges, and action plans to prevent delays in patient access to testing and treatment based on expert opinion. Results Gaps and differences at multiple levels were identified across the four countries. These included variability in the local HER2-low epidemiology data, certification of pathology laboratories and quality control, and reimbursement conditions of testing and anticancer drugs for HER2-negative mBC. While clinical decisions were aligned to international guidelines in use, optimal access to testing and innovative treatment was restricted due to significant delays in reimbursement or limitative reimbursement conditions. Conclusions Preventing delays in HER2-low mBC patient access to diagnosis and novel treatments is crucial to optimize outcomes. Multidisciplinary joint efforts and pro-active discussions between clinicians and decision makers are needed to improve care of HER2-low mBC patients in CEE countries.

e13062 Background: The efficacy and safety of abemaciclib in patients (pts) with HR+/HER2− metastatic breast cancer (MBC) was demonstrated in the MONARCH clinical trials; however, real-world evidence is lacking, particularly in elderly pts. The dose reduction strategy used in the MONARCH trials has been shown to be an effective way of managing toxicity without compromising survival. Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the association between abemaciclib dose reduction and survival. Methods: The efficacy and safety of abemaciclib in patients (pts) with HR+/HER2− metastatic breast cancer (MBC) was demonstrated in the MONARCH clinical trials; however, real-world evidence is lacking, particularly in elderly pts. The dose reduction strategy used in the MONARCH trials has been shown to be an effective way of managing toxicity without compromising survival. Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the association between abemaciclib dose reduction and survival. Results: The median age of 134 pts was 62 yrs (IQR, 54-71), with 40 pts (29.9%) older than 70 yrs. Median rwPFS (mrwPFS) with abemaciclib + endocrine therapy in the ≥70 vs <70 age group was 15 vs 17 months (HR:1.1, 95% CI 0.70-1.76; p=0.65) and median OS (mOS) was 25 vs 34 months (HR:1.4, 95% CI 0.82-2.39, p=0.21). The most common rwAEs are shown (Table). Abemaciclib dose reductions occurred in 40% of pts ≥70 yrs of age compared to 28% of younger pts (χ2 (1)=1.98; p=0.22). There was no difference in mrwPFS between pts who had a dose reduction and those who did not (mrwPFS 15 vs 17 months (HR: 1.03, 95% CI 0.65-1.63, p=0.91) and mOS 28 vs 30 months (HR: 1.16, 95% CI 0.68-1.99; p=0.58)). Conclusions: The results of our study support the efficacy and safety of abemaciclib treatment in pts with HR+/HER2- MBC in real-world clinical practice. Age did not appear to be an important factor associated with higher rates of toxicity and similar efficacy of abemaciclib was demonstrated in the elderly pts population compared to younger pts. Importantly, abemaciclib dose reductions did not compromise survival. Clinical trial information: ERIDNPVO-0060/2022. [Table: see text]

Abstract Background: Metaplastic breast cancer (MBC) is a rare malignancy that accounts for up to 1% of all primary invasive breast carcinomas (BC). It is histologically heterogeneous, usually presents with a triple-negative phenotype and comprises low-grade and high-grade (HG) variants. HG variants have a higher risk of recurrence and a shorter disease-free and overall survival compared to other BC subtypes. Our research aimed to estimate the prevalence of HG-MBC among the Slovenian population and determine the characteristics of patients (pts) and tumours and the disease outcome. Patients and methods: Our retrospective study included pts diagnosed with HG-MBC at the Institute of Oncology Ljubljana from January 1983 until January 2021. Clinicopathologic characteristics such as tumour subtype, size and grade, nodal status, hormonal receptors (HR) and HER-2 status, lymphovascular invasion (LVI), tumour-infiltrating lymphocytes (TIL) and presence of germline BRCA mutation status were determined. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model examined the association between risk factors and survival outcomes. Results: We evaluated 113 HG-MBC pts among a total of 27700 pts diagnosed with BC over 38 years (0.41%). The median age was 61.6 years (range 29.7 -93.9), majority of pts were postmenopausal (78.69%). The median follow-up was 15.5 years. The most common tumour subtype in our cohort was mixed MBC (53 cases, 46.9%), followed by MBC with mesenchymal differentiation (24 cases, 21.2%), squamous cell carcinoma (20 cases, 17.7%) and spindle cell carcinoma (16 cases, 14.2%). From the 113 evaluated pts, we obtained data about the stage in 105 pts, pathological tumour size in 100 pts, number of positive lymph nodes in 99 pts, HR status in 95 pts, HER2 status in 76 pts, grade in 97 pts, LVI in 85 pts, MIB-1 in 41 pts and TIL in 77 pts. At diagnosis, 17/105 pts (16.2%) had stage I disease, 59/105 pts (56.2%) stage II, 25/105 pts (23.8%) stage III and 4/105 pts (3,8%) stage IV. Most tumours were poorly differentiated (90/97, 92.2%) without LVI (60/85, 70.6%). Only 6/95 (6,3%) pts had positive HR, 7/76 (9.2%) pts had positive HER-2 status and 8/77(10.4%) pts intensive TIL. Overall, 13 pts were tested for BRCA germline mutation, among which only 1 (7,7%) had BRCA1 mutation. Modified radical mastectomy was the most frequent type of surgery (63.5%); 49.5% of the patients received radiotherapy. In total, 66/113 pts received CT: from 1983 to 2000, 16/36 (44.4%), and after 2000 50/77 (74.9%). In the first period, most pts received CMF (14/16; 87.5%) and anthracyclines and taxanes (27/50; 54%) in the second period. The disease progressed at 37 pts. At 19 pts, new malignancies were found. 55 pts died, 37 of them because of BC. Five- and 10-year disease-free survival (DFS) was 61.7% and 54.1%, while 5-and 10-year overall survival (OS) was 67.1 % and 56.7%, respectively. However, DFS and OS did not differ between the pre-2000 and post-2000 periods. The best outcome was found in pts with squamous cell carcinoma (5- and 10-year DFS 83.5% and 77.0% and 5-and 10- year OS 89.4 % and 83.0%). A subtype of MBC (squamous cell vs other) was the only predictive factor in multivariate analysis for both DFS (HR 0.21; 95% CI 0.05-0.92; p = 0.038 and OS (HR 0.27; 95%CI 0.09-0.78; p = 0.016), no association was seen between survival and tumour size, nodal status, stage, HR and HER2 status, grade, LVI and TILs. Visceral organs were the most common localization of distant metastases (21/37, 56.8%). Metastases in CNS occurred in 9/37 (24.3%) pts. Median OS after the first progression was only 0.9 years. Conclusions: The proportion of HG-MBC in our cohort of pts is 0.41%. Disease outcomes are poor; the 10-year OS of pts with early HG-MBC is only 56.6% and has not improved during the last decades. Squamous cell differentiation predicts a better outcome and is the only independent predictive factor of DFS and OS among HG-MBC pts. Citation Format: Maša Auprih, Gorana Gasljevic, Eva Setina, Anja Zizek, Simona Borstnar. Metaplastic breast cancer: a single center retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-04.

Background Although anxiety and depression are important determinants of mental health, the literature in this area is sparse as most studies focus on the period during treatment. Mental health problems can affect cancer recovery as well as quality of life and survival. In this cross-sectional study, we investigated the prevalence of anxiety and depression in Slovenian cancer survivors after treatment and assessed the associated correlates during the COVID-19 pandemic.Methods From September 2021 to January 2022, we collected data from 430 breast cancer survivors one to five years after receiving post-local treatment and (neo)adjuvant chemotherapy. We used the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depression levels. Multivariate linear regression was used to identify factors associated with higher levels of anxiety and depression.Results Key findings from this study are increased levels of psychological distress and identification of relevant factors associated with those elevated levels. Approximately one-third of breast cancer survivors exhibited symptoms of elevated anxiety and depression, with one in eight meeting clinical thresholds. Multivariate linear regression revealed that age, lower quality of life, heightened fear of cancer recurrence (FCR), reduced resilience, limited social support, and unmet psychosocial and emotional needs correlated with increased anxiety symptoms. Additionally, lower quality of life, higher FCR, diminished resilience, and limited social support were associated with higher depression symptomatology.Conclusions Our study of Slovenian breast cancer survivors one to five years post-treatment observed a significant increase in anxiety and depression symptoms, possibly exacerbated by the COVID-19 pandemic. The demographic and psychosocial factors identified in this study offer valuable insights for future research. The study emphasises the importance of recognising and addressing the psychological needs of breast cancer survivors and the need to follow them throughout their cancer journey.

e13123 Background: Eribulin mesylate (eribulin) is a microtubule inhibitor and a synthetic analog of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin was approved based on the randomized Phase 3 EMBRACE clinical trial, which showed an improvement in survival compared to chemotherapy (CT) of the physician's choice. The efficacy and safety of eribulin treatment in real-world settings has been reported in several studies: Korean and Chinese multicenter retrospective studies and a meta-analysis from 2020. Methods: We included all patients treated with eribulin between January 24, 2013 and September 14, 2022 at the Institute of Oncology Ljubljana (85.4% of patients) and University Medical Centre Maribor (14.6%). Clinical data were collected retrospectively from paper and electronic patient records. The primary endpoints were median progression-free survival (PFS), overall survival (OS), response rates and safety. We performed a descriptive statistical analysis and a survival analysis using the Kaplan-Meier method. Results: 205 patients, whose average age was 58.6 (29-88) years, were included in the study. The majority (79%) had a hormone receptor (HR+) positive tumor, 12.2% were HER2 positive and 16.6% were triple negative. 32/205 (15.6%) were primary metastatic. Of the remaining 173 patients, 160/173 (92.4%) received adjuvant therapy, of which 15% received hormone therapy, 23.1% received CT and 61.9% received both. At the start of treatment with eribulin, 84.9% had visceral tumors and 14.6% had tumors in the CNS. The median number of all treatment lines was 6 (range 2–15) and the median number of CT lines was 4 (0–13). The ECOG performance status was: 0 in 4.9%, 1 in 53.2%, 2 in 35.1% and 3 in 4.9% and 4 in 0.5% of patients. The objective response rate was 7.3% and clinical benefit was achieved in 27.3%. The median CT line in which eribulin was used was the fourth (1–10). Eribulin was used as the last CT line in half of the patients. The median PFS was 3.01 months (95% confidence interval 2.56–3.47) and the median OS was 6.68 months (95% confidence interval 5.60–7.77). Patients who received eribulin in the first 3 lines of treatment had a better OS than those who received eribulin in later lines. Adverse events (AEs) occurred in 52.7%. Eribulin therapy was discontinued due to AEs in 18.5% of patients. The most common AE was fatigue (25.9%), followed by neuropathy and neutropenia (22.9% and 18%). Conclusions: In our retrospective analysis, we found significantly worse results of treatment with eribulin than in previous studies. In our population, eribulin was used in the late stages of treatment and in older patients with poorer performance status. The proportion of patients with visceral and CNS tumors was higher. The side effects were comparable.

Antibody-drug conjugates (ADCs) are a new generation of drugs that currently represent one of the most effective treatment options for cancer. ADCs target a specific target (antigen) that is selectively expressed on a tumour cell. Binding ofADCs to a tumour cell results in targeted intracellular delivery of cytotoxic drugs which causes cell death. An ADC called trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in several clinical trials called DESTINY. Initial data were available for patients with metastatic HER2-positive breast cancer, followed by data on otherHER2-po- sitive solid cancers and breast cancer with low HER2 expression. In this article, we present the first data on the efficacy and safety of T-DXd in Slovenia. We conducted a retrospective study of patients treated with T-DXd at the Institute of Oncology Ljubljana from November 2021 to April2024. We observed good responses to treatment (objective response 59% in HER2-positive breast cancer, 38% in other HER2-positive solid cancers and 33% in breast cancer with low HER2 expression). After a short median follow-up of 8.8 (95% CI 0.8-33.3) months, real world progression-free survival (rwPFS) was 13 months in HER2-positive breast cancer, 5.8 months in HER2-low breast cancer, and 7.7months in other HER2 positive orHER2-mutated solid cancers. The safety profile was consistent with that reported in the registration studies, with the exception of pneumonitis, which was reported in a much lower percentage (only 1%). We can conclude that the response rate to T-DXd is high despite the late treatment lines and the heterogeneous population, while rwPFS assessment is unreliable due to the short observation period.

Triple-negative breast cancer (TNBC) accounts for about 10-20% of all breast cancer cases and is associated with an unfavorable prognosis. Until recently, treatment options for TNBC were limited to chemotherapy. A new successful systemic treatment is immunotherapy with immune checkpoint inhibitors, but new tumor-specific biomarkers are needed to improve patient outcomes. Cannabinoids show antitumor activity in most preclinical studies in TNBC models and do not appear to have adverse effects on chemotherapy. Clinical data are needed to evaluate efficacy and safety in humans. Importantly, the endocannabinoid system is linked to the immune system and immunosuppression. Therefore, cannabinoid receptors could be a potential biomarker for immune checkpoint inhibitor therapy or a novel mechanism to reverse resistance to immunotherapy. In this article, we provide an overview of the currently available information on how cannabinoids may influence standard therapy in TNBC.