BACKGROUND:Surgical possibilities and implant options in reconstructive and corrective breast surgery have expanded considerably, making comparative outcome data essential for informed preoperative decision-making. OBJECTIVES:This study presents and compares a single surgeon's long-term experience with Becker expander and fixed-volume implants in a large patient series, supplemented by a systematic review of the literature on postoperative and long-term complications. METHODS:Records of 183 patients (247 implants) who underwent reconstructive or corrective breast surgery using fixed-volume or Becker expander implants in a single-surgeon setting were retrospectively reviewed. Patient characteristics, risk factors, and surgical indications were analyzed within each implant group. Complications were categorized as minor or major, the latter defined as any event leading to revision surgery and implant loss. Results were compared to other large (n > 100) retrospective studies identified through a PubMed literature review. RESULTS:Cohorts of 90 patients with 112 Becker expander implants and 93 patients with 135 fixed-volume implants were compared. Groups did not differ significantly in patient history or risk factors. Complications were documented over a minimum follow-up of 24 months (median 5.87 years). Overall complication rates did not differ significantly between groups (31.25% vs. 32.59%, p ≥ 0.05). Major complications leading to implant loss were significantly more frequent in the Becker group (9.73% vs. 2.21%, p < 0.05), though this difference could not be reproduced in any individual subgroup. CONCLUSIONS:Despite the higher rate of major complications, overall complication rates in both groups were lower than average rates reported in the literature. Becker expanders remain a valid alternative to fixed-volume implants in single-stage reconstruction when patient selection is made carefully and aesthetic expectations favor volume adjustability.

Focal breast lesions are observed in up to 5.8% of CT examinations performed in female patients for a wide variety of indications not affecting the breast. To simplify and standardize the further procedure in the case of breast masses visualized by computed tomography (CT), an easy and robust diagnostic approach in assigning surely benign findings, uncertain findings and probably malignant findings is warranted. We aimed (1) to determine the diagnostic gain of quantitative measurements of the iodine content in breast masses visualized in contrast-enhanced dual energy (DE) CT examinations additional to the assessment of qualitative image features; and (2) to generate an interactive hierarchical decision tree allowing to assess the individual probability of benign or malignant findings. All contrast-enhanced DECT examinations performed in adult females from January 2018 to December 2020 were retrospectively screened for solid breast masses. Subsequently, the DECT images with confirmed breast masses were evaluated independently by 3 radiologists experienced in breast imaging using a structured questionnaire. First, the image characteristics of the ACR-BIRADS atlas on MRI were queried, and an assessment of the probability of benignancy or malignancy was requested. Second, the iodine content in the breast masses was interactively measured, and the readers were asked to provide a further assessment of the biological identity. Third, a decision tree was developed using a nonparametric supervised (machine) learning algorithm. During the survey period, 5.591 contrast-enhanced DECT examinations of the chest were carried out in adult female patients. Six hundred eighty-seven DECTs (12.3%) displayed breast masses. The study group comprised 415 female patients (7.4%) with a benign or malignant breast mass confirmed by histology (155, 37.4%), a constant CT-course of ≥2 years without interfering therapy (202, 48.8%) and/or noninvasive breast imaging (57, 13.8%). Neither in the first step nor in the second step of the evaluations a cancer confirmed in the reference standard was classified as certainly benign. Subgroup analyses showed that the combined qualitative and quantitative approach was diagnostically superior compared with the sole descriptor-based assessments in 757 assessments of DECT evaluations with ACR 1+2 breast densities (AUC = 0.961 vs 0.924, lower bound 0.940 vs 0.893, upper bounds 0.982 vs 0.956, P = 0.001) and for the 541 assessments of DECT examinations visualizing masses in denser ACR 3+4 parenchyma (AUC = 0.972 vs 0.948, lower bound 0.953 vs 0.923, upper bound 0.991 vs 0.974, P = 0.043). Including iodine content into the descriptive image evaluations proved to be superior to the solely descriptor-based assessments in 456 assessments of lesions with >5 to 10 mm diameter and in 370 assessments of lesions with >10 to 20 mm (P = 0.002, 0.002 and 0.018, respectively). Mass contour proved to be the first hierarchical decision level of the interactive classification tree for the differentiation of benign and malignant lesions developed in step 3. In the second hierarchical level, automatically generated classifications of the iodine content allowed to generate 3 diagnostic predictors analogous to the BIRADS classification with a depth of 2 ramifications. Information on the iodine content of breast masses detected by DECT increases diagnostic certainty in the assessment of the biological significance of the lesions. The presented nonparametric decision tree may be helpful in interactively combining semantic and quantitative image data in clinical routine diagnostics of breast masses in spectral CT examinations.

LBA515 Background: Dose-dense anthracycline-taxane chemotherapy (CTx) is standard for high-risk early breast cancer (eBC) and is often given in the neoadjuvant setting if CTx is clearly indicated (e.g., recurrence score, RS > 25 and/or > 4 positive lymph nodes by imaging) or if downstaging is needed. While dose-dense CTx improves outcomes irrespective of hormone receptor (HR) status in meta-analyses, its benefit in node-negative HR+ eBC appears limited. Further meta-analyses on neoadjuvant vs adjuvant use, and on mono- vs combined therapy, showed mixed results. These findings highlight an unmet need for a refined treatment selection, informed by the assessment of relative survival benefit. We therefore pooled the WSG ADAPT-HR+/HER2- and PlanB trials to estimate the impact of dose density, anthracycline use, and treatment setting on survival. Methods: Invasive (iDFS), distant disease-free survival (dDFS), and overall survival (OS) were analyzed retrospectively in a pooled analysis of HR+/HER2- patients (pts) in ADAPT-HR+/HER2- (n = 2331) and PlanB (n = 2220) who received chemotherapy and had follow-up data (data cut: Jan 26, 2026). In ADAPT-HR+/HER2-, pts at high-risk received 8× weekly nab-paclitaxel vs. 4× biweekly sb-paclitaxel, followed by epirubicin + cyclophosphamide (EC) in either the neoadjuvant or adjuvant setting. PlanB randomized pts at intermediate- to high-risk to adjuvant 4× EC followed by 4× docetaxel (EC-T) vs. 6× TC. To minimize bias, predefined uniform cross-trial subgroups (RS > 25 any pN; pN2–3 any RS) were considered here, and propensity scoring for non-random allocations (neoadjuvant vs adjuvant CTx in ADAPT-HR+/HER2-, physician choice). Results: This pooled analysis included 1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2-3 eBC. Dose-dense anthracycline or paclitaxel yielded inferior iDFS and dDFS than q3w docetaxel, even after adjustment for cT, age, and grade. This effect, favoring a (longer) docetaxel-based CTx, was present among N2-3 pts with RS ≤25, who showed better iDFS, dDFS, and OS, and among RS > 25 pts (in particular, in N0-1), who showed better dDFS. Informed by these results, we assessed the impact of anthracyclines in PlanB pts with RS > 25 and/or N2-3 and observed no significant survival differences. There was no significant survival difference between neoadjuvant vs adjuvant CTx in the corresponding subset of ADAPT-HR+/HER2- pts, even in propensity-scored analysis. Conclusions: Our exploratory retrospective analysis does not show a significant survival difference by anthracycline use or treatment setting (neoadjuvant vs adjuvant) in high-risk HR+/HER2- eBC pts who are candidates for CTx. Optimal use of dose-dense CTx in the context of docetaxel-based treatment requires further investigation. Clinical trial information: NCT01779206 ; NCT01049425 .

BACKGROUND:Leptomeningeal metastases (LM) in patients with breast cancer (BC) are associated with a dismal prognosis. We explored clinical characteristics and prognostic factors in patients with BC and LM in the German Brain Metastases in Breast Cancer Registry. METHODS:All patients with histologically confirmed BC and diagnosis of LM (defined as the presence of tumor cells in the cerebrospinal fluid, or presence of typical clinical symptoms in combination with typical magnetic resonance imaging findings) were included. RESULTS:A total of 3857 patients were included in the analysis (n = 859 (22.3 %) with LM). Among patients with LM a median progression-free survival was 4.2 months (95 % CI 3.6-4.8), and median overall survival was 5.7 months (95 % CI 4.9-6.7). In the multivariate analysis older age ( ≥ 60 vs. <60 years, Hazard ratio (HR): 1.65, 95 %CI: 1.25-2.18), worse performance status (ECOG 2-4 vs. 0-1 HR: 2.15, 95 %CI: 1.63-2.82), hormone receptor positive/HER2-negative (HR+/HER2-) or triple-negative subtype (HR: 1.54 95CI%: 1.07-2.23 and HR: 1.87, 95 %CI: 1.25-2.81), and higher number of BM (2-3 vs. 1, HR: 1.49, 95 %CI: 1.05-2.11 4) were significantly associated with a higher risk of death. Stereotactic radiotherapy (HR 0.49 95 %CI 0.30-0.79) and whole brain irradiation (HR: 0.58, 95 %CI: 0.42-0.80), endocrine therapy in patients with HR + BC (HR: 0.31, 95 %CI: 0.21-0.45) as well as HER2-targeted therapy for patients with HER2+ BC (HR 0.41, 95 %CI: 0.25-0.68) were associated with a significantly longer survival. CONCLUSIONS:Clinicopathological factors associated with survival can help clinicians identify patients who are candidates for treatment (de)escalation in clinical trials.

Whole-breast radiotherapy (WBRT) after breast-conserving surgery (BCS) in older patients can be challenging due to the increased presence of comorbidities, comedication, the presence of a pacemaker or difficulties in traveling to treatment every day. Challenging times, such as the pandemic, can also lead to RT not being performed despite the indication. Very short treatment regimens are therefor of special interest in this population reducing overall treatment time and radiation exposure. TARGIT-E is a phase II trial investigating intraoperative radiotherapy (IORT) during BCS in elderly patients. We report long-term follow-up results of TARGIT-E. Patients with BC (≥ 70 years, cT1-2, cN0, M0) were enrolled at 28 European centers. A single dose of IORT (20 Gy) was given during BCS. Additional postoperative WBRT was applied if risk factors were present in final histopathology. Primary outcome was local recurrence-free rate (RFR) using the Kaplan–Meier-method. Late toxicities were assessed by LENT-SOMA criteria, and cosmetic outcomes were graded using BCCT.core software. In 591 patients (median follow-up 5.4 years) RFR was 97.6

PURPOSE To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking. METHODS A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia. Patients with mBC (N = 357) were randomly assigned to either a 9-month, twice-weekly, supervised exercise group (EG) or control group (CG). Costs of the exercise program were calculated through a bottom-up approach. Other health care resource use, productivity losses, and quality of life were collected using country-adapted, self-reported questionnaires. Analyses were conducted from a societal perspective with a time horizon of 9 months. Costs were collected and reported in 2021 Euros (€1 = $1.18 US dollars). RESULTS Compared with the CG, EG resulted in a quality-adjusted life-year (QALY) gain of 0.013 (95% CI, –0.02 to 0.05) over a 9-month period. The mean costs of the exercise program were €1,696 per patient with one-on-one supervision (scenario 1) and €609 with one-on-four supervision (scenario 2). These costs were offset by savings in health care and productivity costs, resulting in mean total cost differences of –€163 (scenario 1) and –€1,249 (scenario 2) in favor of EG. The probability of supervised exercise being cost-effective was 65% in scenario 1 and 91% in scenario 2 at a willingness-to-pay threshold of €20,000 per QALY. CONCLUSION Exercise for patients with mBC increases quality of life, decreases costs, and is likely to be cost-effective. Group-based supervision is expected to have even higher cost-savings. Our positive findings can inform reimbursement of supervised exercise interventions for patients with mBC.

Abstract Background New data show that not only HER2-overexpressing breast cancer (BC) tumors but also HER2-low tumors, classically considered as HER2-negative, respond to HER2-targeting antibody–drug-conjugates. Our objective was to analyze the prevalence of HER2-low BC in a pooled analysis of contemporary early BC trials and to evaluate its role as a prognostic factor in terms of survival in comparison to HER2-zero BC. Methods We evaluated 5598 patients with locally HR + /HER2- BC from the screening cohort of WSG-ADAPT-HR + /HER2-, 2592 patients with HR + /HER2- or HR-/HER2- from the adjuvant WSG-PlanB trial, and 336 patients from the WSG-ADAPT-TN trial. Central HER2 testing was performed prospectively in WSG-ADAPT and retrospectively in WSG-PlanB. Following ASCO/CAP guidelines, HER2-low status was defined as immunohistochemistry (IHC) 1 + or 2 + and in situ hybridization (ISH)-negative, and HER2-zero was defined as IHC 0. Agreement between HER2 assessments was evaluated with Cohen’s kappa coefficient, and effects of HER2 status on pathological complete response (pCR) and on survival were analyzed with logistic regression and Cox proportional hazards models, respectively. Findings In WSG-ADAPT-HR + /HER2-, 3198 (64.6%) tumors were HER2-low by the central and 3096 (55.6%) by the local histology (agreement for HER2-low status was 61.0%). In HR + /HER2- cases from WSG-PlanB, 601 tumors (28.7%) were HER2-low. In both cohorts, HER2-low status was significantly associated with higher ERBB2 mRNA expression by Oncotype DX test in comparison to HER2-zero: mean 9.3 vs. 9.1 (p < .001) by local HER2 assessment in WSG-ADAPT and mean 9.2 vs. 8.8 (p < .001) in WSG-PlanB. Furthermore, patients with HER2-low tumors in WSG-ADAPT-HR + /HER2- significantly less often had a pCR compared to the HER2-zero tumors (p = .015). No significant difference was observed in (invasive and/or distant) disease-free survival (DFS) between centrally HER2-low and HER2-zero tumors in both HR + /HER2- cohorts (WSG-ADAPT-HR + /HER2- distant DFS: unadjusted HR = 1.06, 95%CI 0.83–1.36, similar results for local assessment; WSG-PlanB DFS: unadjusted HR = 1.28, 95%CI 0.91–1.82). In the HR-/HER2- WSG-PlanB cohort, centrally HER2-low tumors (10.5%) were associated with better DFS (unadjusted HR = 0.21, 95%CI 0.05–0.83), this association was not observed in the WSG-ADAPT-TN. Conclusion The prevalence of HER2-low status varied between the analyzed trials. Our results show that survival does not differ between HER2-low and HER2-zero tumors in HR + /HER2- cohorts; however, HER2-low status appears to have an inconsistent impact on survival in TNBC. Therefore, our findings do not support the characterization of HER2-low status as a distinct BC subtype.

Background/Aim: This study examined the influence of preoperative MRI on the choice of implant volume in patients undergoing subcutaneous mastectomy with immediate breast reconstruction. It was postulated that preoperative MRI scans can adequately estimate glandular tissue, which in turn correlates with implant size. Patients and Methods: Preoperative and postoperative MRI scans were used in oncological and prophylactical subcutaneous mastectomy scenarios in 67 cases at the Department of Gynaecology, Breast Cancer Center, University of Cologne, Germany. The preoperative MRI was used to estimate the resected tissue and the postoperative MRI was used to scan for residual glandular tissue. In addition, a correlation found by Malter et al. in 2021 was evaluated with the available data. Results: Preoperative MRIs result in an adequate estimation of resected tissue. This in turn correlates with implant volume. The correlation by Malter et al. also holds when estimating implant volume. The likelihood of residual gland was low if the preoperatively estimate volume was removed. Conclusion: Our results indicate that the use of preoperative and postoperative MRI scans for subcutaneous mastectomies is advantageous. We suggest a routine estimation of glandular tissue, especially for small breasts.

Objective: We aimed to asses, in a clinical setting, whether the newly available quantitative evaluation of electron density (ED) in spectral CT examinations of the breast provide information on the biological identity of solid breast masses and whether ED maps yield added value to the diagnostic information of iodine maps and Zeff maps calculated from the same CT image datasets. Methods: All patients at the University Breast Cancer Center who underwent a clinically indicated Dual Layer Computed Tomography (DLCT) examination for staging of invasive breast cancer from 2018 to 2020 were prospectively included. Iodine concentration maps, Zeff maps and ED maps were automatically reconstructed from the DLCT datasets. Region of interest (ROI) based evaluations in the breast target lesions and in the aorta were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Case-by-case evaluations were carried independently by 2 of 4 radiologists for each examination, respectively. Statistical analysis derived from the ROIs was done by calculating ROC/AUC curves and Youden indices. Results: The evaluations comprised 166 DLCT examinations. In the ED maps the measurements in the breast target lesions yielded Youden cutpoints of 104.0% (reader 1) and 103.8% (reader 2) resulting in AUCs of 0.63 and 0.67 at the empirical cutpoints. The variables "Zeff" and "iodine content" derived from the target lesions showed superior diagnostical results, with a Youden cutpoint of 8.0 mg/ml in the iodine maps and cutpoints of 1.1/1.2 in the Zeff maps the AUCs ranging from 0.84 to 0.85 (p = 0.023 to <0.000). The computational combination of Zeff and ED measurements in the target lesions yielded a slight AUC increase (readers 1: 0.85-0.87; readers 2: 0.84-0.94). The ratios of the measured values in the target lesions normalized to the values measured in the aorta showed comparable results. The AUCs of ED derived from the cutpoints showed inferior results to those derived from the Zeff maps and iodine maps (ED: 0.64 and 0.66 for reader 1 and 2; Zeff: 0.86 for both readers; iodine content: 0.89 and 0.86 for reader 1 and 2, respectively). The computational combination of the ED results and the Zeff measurements did not lead to a clinically relevant diagnostic gain with AUCs ranging from 0.86 to 0.88. Conclusions: Quantitative assessments of Zeff, iodine content and ED all targeting the physical and chemical aspects of iodine uptake in solid breast masses confirmed diagnostically robust cutpoints for the differentiation of benign and malignant findings (Zeff < 7.7, iodine content of <0.8 mg/ml). The evaluations of the ED did not indicate any added diagnostic value beyond the quantitative assessments of Zeff and iodine content. Further research is warranted to develop suitable clinical indications for the use of ED maps.

Abstract Introduction: Autologous breast reconstruction using the deep inferior epigastric perforator flap has excellent success rates and a natural aesthetic result. Therefore, this method and its management are of great importance in modern oncoplastic surgery. In particular, women who have undergone radiation therapy after mastectomy benefit from this satisfactory and usually uncomplicated method of breast reconstruction. To achieve a desirable outcome, the effects of blood loss and blood pressure management may play an important role. In this analysis, we hypothesize that neither postoperative blood pressure management (using catecholamines) nor the amount of blood loss (defined by the median hemoglobin level difference) will worsen the surgical outcome or increase the complication rate. Patients and Methods: We performed a multicenter, multisurgeon retrospective analysis with the following primary end points: intraoperative blood loss and postoperative blood pressure management. Secondary endpoints included serious complications including flap loss and minor complications. Patients (n=194) were included from 2014-2018 at St. Antonius Hospital in Eschweiler and from 2016 to July 2018 at the Cologne Municipal Breast Cancer Center in Holweide. Patients underwent either unilateral (n=180) or bilateral (n=13) breast reconstructions with DIEP flaps, resulting in a total of n=206 cases. The subgroup regarding blood pressure management was defined by cohorts with or without catecholamine administration and included all n=206 cases. Blood loss was defined by median hemoglobin level difference and could be calculated in n=199 cases. The cohorts of the two subgroups were comparable. Results: Six flap losses were detected in a total of 206 cases (2.9%). The distribution of flap losses in the blood pressure management subgroup was not statistically significant (p=.67), while the test was not available for the blood loss subgroup. Furthermore, the analysis showed that there were no significant differences in the rates of overall complications related to the amount of blood loss intraoperatively (p= .06) or blood pressure management postoperatively (p= .19). Conclusion: DIEP flap surgery is a safe method for autologous breast reconstruction, independent of blood loss and blood pressure management. Citation Format: Hanna Fritsch, Cosima Schreiber, Wolfram Malter, Matthias Warm, Max Zinser, Alexander Bach, Christian Eichler. The impact of blood loss and blood pressure management in DIEP flap surgery– a retrospective analysis of 206 patients [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 PO2-22-09.

In DIEP flap surgery the impact of perioperative blood loss and blood pressure management may play a major role. In this analysis, it is hypothesized, that neither postoperative blood pressure management (using catecholamines) nor the amount of blood loss (defined by the median hemoglobin level difference) worsen the surgical outcome or increase the rate of complications.

INTRODUCTION:Breast cancer patients (BCP) experience considerable side effects during and after treatment. Several studies have shown positive effects of exercise on therapy-related side-effects such as loss of muscle strength, loss of bone mineral density, lymphedema, and several elements of quality of life (QoL). Resistance exercise has proven effective and beneficial for BCP; however, optimal individual training parameters remain to be determined. METHODS:The aim of our study was to implement an adaptive, progressive, supervised resistance protocol for BCPs during chemotherapy, improving muscle strength, physical condition, and overall QoL while reducing therapy-induced side-effects. Forty patients receiving adjuvant chemotherapy were included 6-12 weeks post-OP. Twenty patients underwent high intensity resistance-training twice a week for 12 weeks, and the control group received usual care. RESULTS:Strength parameters improved significantly in the intervention group and in different scales of QoL. We documented a cyclic performance level dependent on the number of days after treatment. CONCLUSION:Adaptive resistance training with simple training control mechanisms proved to be effective regarding optimal intensity in each training session and needs to be implemented in further studies in order to guarantee adequate loads in accordance to the training protocols.

INTRODUCTION & AIMS Exercise has been proven safe and effective for patients with breast cancer in the curative setting, however evidence in patients with metastatic breast cancer (mBC) is scarce. The aim of the PREFERABLE - EFFECT study (NCT04120298) was to evaluate the effects of a structured exercise program on fatigue, health-related quality of life (HRQoL), and other cancer- and treatment-related side effects in patients with mBC. METHODS The randomized controlled trial included patients with mBC from five European countries (Germany, Spain, Netherlands, Poland, Sweden) and Australia. Participants were randomly assigned to usual care (UC) or a 9-month supervised and individualized exercise program (EX) involving twice weekly aerobic, resistance, and balance exercises. The primary outcomes, physical fatigue (EORTC QLQ-FA12 subscale) and HRQoL (EORTC QLQ-C30 summary score) were assessed at baseline, 3, 6, and 9 months. Among other physical fitness outcomes, maximal short exercise capacity was assessed with the Steep Ramp Test. Changes from baseline to 3, 6 (primary endpoint) and 9 months were compared between groups using adjusted mixed models for repeated measures. RESULTS A total of 357 patients were randomized (EX=178, UC=179). On average, participants were 55.4 years of age (SD=11.1) and 73.9% had bone metastases. EX resulted in a significant reduction in physical fatigue (-5.3 [-10.0; -0.6], p=.027, ES=0.22) and improvement in HRQoL (+4.8 [2.2; 7.4], p=.0003, ES=0.33) compared to UC at 6 months (primary endpoint), as well as at 3 and 9 months. EX also improved physical fitness (+24.3 Watts, [15.5; 33.1], ES=0.42, at 6 months) and numerous relevant QLQ-C30 scales, including social functioning, pain, and dyspnoea. CONCLUSION This large multinational study demonstrates that supervised exercise improves fatigue, HRQoL, and other clinically relevant outcomes in patients with mBC. Based on these findings, supervised exercise should be recommended to patients with mBC.

Physical exercise both during and after curative cancer treatment has been shown to reduce side effects. Evidence in the metastatic cancer setting is scarce, and interventions that improve health-related quality of life (HRQOL) are much needed for patients with metastatic breast cancer (MBC). The multinational randomized controlled PREFERABLE-EFFECT trial assessed the effects of exercise on fatigue and HRQOL in patients with MBC. In total, 357 patients with MBC and a life expectancy of >= 6 months but without unstable bone metastases were recruited at eight study centers across five European countries and Australia. Participants were randomly assigned (1:1) to usual care (control group, n = 179) or a 9-month supervised exercise program (exercise group, n = 178). Intervention effects on physical fatigue (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-FA12 scale) and HRQOL (EORTC QLQ-C30 summary score) were determined by comparing the change from baseline to 3, 6 (primary timepoint) and 9 months between groups using mixed models for repeated measures, adjusted for baseline values of the outcome, line of treatment (first or second versus third or higher) and study center. Exercise resulted in significant positive effects on both primary outcomes. Physical fatigue was significantly lower (-5.3 (95% confidence interval (CI), -10.0 to -0.6), Bonferroni-Holm-adjusted P = 0.027; Cohen's effect size, 0.22) and HRQOL significantly higher (4.8 (95% CI, 2.2-7.4), Bonferroni-Holm-adjusted P = 0.0003; effect size, 0.33) in the exercise group than in the control group at 6 months. Two serious adverse events occurred (that is, fractures), but both were not related to bone metastases. These results demonstrate that supervised exercise has positive effects on physical fatigue and HRQOL in patients with MBC and should be recommended as part of supportive care.ClinicalTrials.gov Identifier: NCT04120298. In this large interventional, randomized controlled trial, structured and individualized exercise in patients with metastatic breast cancer led to lower levels of fatigue and improved health-related quality of life.

Objective: To asses the correlation of data derived from dual-layer (DL)-CT material-maps and breast MRI data with molecular biomarkers in invasive breast carcinomas. Methods: All patients at the University Breast Cancer Center who underwent a clinically indicated DLCT-scan and a breast MRI for staging of invasive ductal breast cancer from 2016 to 2020 were prospectively included. Iodine concentration-maps, and Zeffective-maps were reconstructed from the CT-datasets. T1w- and T2w-signal intensities, ADC and the clustered shapes of the dynamic-curves (washout, plateau, persistent) were derived from the MRI-datasets. ROI-based evaluations of the cancers and the reference "musculature" were performed semiautomatically in identical anatomical positions using dedicated evaluation software. Statistical analysis was essentially descriptive using Spearman ' s rank correlation and (multivariable) partial correlation. Results: The signal intensities measured in the 3rd phase of the contrast dynamics correlated at an intermediate level of significance with the iodine content and the Zeffective-values derived from the breast target lesions (Spearman ' s rank correlation-coefficient r = 0.237/0.236, p = 0.002/0.003). The bivariate and the multivariate analyses displayed correlations of an intermediate significance level of the iodine content and the Zeff-values measured in the breast target lesions with immunhistochemical subtyping (r = 0.211-0.243, p = 0.002-0.009, respectively). The Zeff-values showed the strongest correlations when normalized to the values measured in the musculature and in the aorta (r = -0.237 to 0.305, r = <0.001-0.003). The MRI-assessments showed correlations of intermediate to high significance and low to intermediate significance between the ratios of the T2w-signal intensities and the trends of the dynamic curves measured in the breast target lesions and in musculature and immunohistochemical cancer subtyping, respectively (T2w: r = 0.232-0.249, p = 0.003/0.002; dynamics: r = -0.322/-0.245, p = <0.001/0.002). The ratios of the clustered trends of the dynamic curves measured in the breast target lesions and in musculature correlated with tumor grading on intermediate significance level (r = -0.213 and 0.194, p = 0.007/0.016) and with Ki-67 on a low significance level (bivariate analysis: r = -0.160, p = 0.040). There was only a weak correlation between the ADC-values measured in the breast target lesions and HER2-expression (bivariate ansalysis: r = 0.191, p = 0.030). Conclusions: Our preliminary results indicate that evaluation of perfusion based DLCT-data and MRI-biomarkers show correlations with the immunhistochemical subtyping of invasive ductal breast carcinomas. Further clinical research is warranted in order to validate the value of the results and define clinical situations in which the use of the described DLCT-biomaker and MRI biomarkers may be helpful in clinical patient care.