Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study.

BRAWO, a real-world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2- advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2-ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE. A multivariate-analysis using Cox proportional hazard model was built to identify predictors of progression. Overall, 2100 patients were enrolled (August 2012-December 2017); 2074 were evaluable for efficacy and safety analyses. Majority of patients (60.6%) received EVE + EXE as first (28.7%) or second-line (31.9%) therapy. Visceral metastases were present in 54.1% patients. Median progression-free survival (mPFS) reported as 6.6 months (95%CI: 6.3-7.0). Multivariate-analysis in a subset of patients (n = 1837) found higher body mass index (BMI) and non-visceral metastases to be independent predictors of favorable PFS. Patients with a BMI of 20 to <25 had a mPFS of 6.0 (95%CI: 5.4-6.4) and those with a BMI ≥30 had mPFS of 8.5 (95%CI: 6.9-9.9). 41.2% patients achieved stable disease and 7.3% partial response. No major changes were observed QoL; 86.4% patients received stomatitis prophylaxis and 41.4% experienced EVE related AEs of stomatitis, mainly low grade. AEs occurred in 91.2% of patients, of which stomatitis (42.6%) and fatigue (19.8%) were most frequent. The BRAWO study provides real-world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2- ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.

Physical activity levels are positively related to progression-free survival and reduced adverse events in advanced ER+ breast cancer.

BACKGROUND: Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case-control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. METHODS: In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3 months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3 months until study termination. RESULTS: Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p = .0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. CONCLUSIONS: Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. TRIAL REGISTRATION: EUPAS9462. Registered 30th October 2012 "retrospectively registered."

Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial.

BACKGROUND: The phenotypes of tumor cells change during disease progression, but invasive rebiopsies of metastatic lesions are not always feasible. Here we aimed to determine whether initially HER2-negative metastatic breast cancer (MBC) patients with HER2-positive circulating tumor cells (CTCs) benefit from a HER2-targeted therapy. METHODS: The open-label, interventional randomized phase III clinical trial (EudraCT Number 2010-024238-46, CliniclTrials.gov Identifier: NCT01619111) recruited from March 2012 until September 2019 with a follow-up duration of 19.5 months. It was a multicenter clinical trial with 94 participating German study centers. A total of 2137 patients with HER2-negative MBC were screened for HER2-positive CTCs with a final modified intention-to-treat population of 101 patients. Eligible patients were randomized to standard therapy with or without lapatinib. Primary study endpoints included CTC clearance (no CTCs at the end of treatment) and secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: In both treatment arms CTC clearance at first follow-up visit-although not being significantly different for both arms at any time point-was significantly associated with improved OS (42.4 vs 14.1 months; P = 0.002). Patients treated additionally with lapatinib had a significantly improved OS over patients receiving standard treatment (20.5 vs 9.1 months, P = 0.009). CONCLUSIONS: DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of MBC cancer patients to HER2-targeting therapies. The OS benefit could be related to lapatinib, but further studies are required to prove this clinical observation. ClinicalTrials.gov Registration Number: NCT01619111.

The impact of physical activity on progression-free and overall survival in metastatic breast cancer based on molecular subtype.

BACKGROUND: Although adequate physical activity has been shown to be beneficial in early breast cancer, evidence in metastatic breast cancer is sparse and contradictory, which could be related to distinct effects of physical activity on the different molecular cancer subtypes. Therefore, we here evaluated the effect of physical activity on progression-free and overall survival (PFS, OS) in metastatic breast cancer, specifically looking at molecular subtypes. METHODS: International Physical Activity Questionnaire (IPAQ) questionnaires, filled out by patients enrolled in the prospective PRAEGNANT registry (NCT02338167; n = 1,270) were used to calculate metabolic equivalent task (MET) minutes, which were subsequently categorized into low (n = 138), moderate (n = 995) or high IPAQ categories (n = 137). Cox regression analyses were used to evaluate the impact of IPAQ categories and its interaction with molecular subtypes on PFS and OS. RESULTS: Patient and tumor characteristics were equally distributed across IPAQ categories. HER2pos, HRpos and TNBC were present in 23.1%, 65.7% and 11.2% of patients, respectively. IPAQ scores did not have an impact on PFS and OS in addition to established prognostic factors, either overall or in particular molecular subtypes (PFS: p = 0.33 and OS: p = 0.08, likelihood ratio test). Exploratory analyses showed higher overall survival rates for high IPAQ categories compared to low/moderate IPAQ categories in luminal B-like breast cancer. CONCLUSIONS: Self-reported physical activity using the IPAQ questionnaire did not significantly affect PFS or OS in patients suffering from metastatic breast cancer. Nevertheless, some hypothesis-generating differences between molecular subtypes could be observed, which may be interesting to evaluate further.

Ovarian Cancer Retrospective European (O'CaRE) study: first-line outcomes by number of risk factors for progression.

Aim: The Ovarian Cancer Retrospective European (O'CaRE) study assessed the cumulative impact of high-risk factors on progression-free survival (PFS) and overall survival (OS) following first-line treatment in patients diagnosed with advanced ovarian cancer.Patients & methods: Medical records were collected from five European countries (2014 and 2015). Patients were grouped by number of high-risk factors: stage IV diagnosis, no known BRCA mutation, interval debulking surgery or no surgery, or visible residual disease.Results: Our analysis included 405 patients grouped based on having one (20.4%); two (32.3%); three (33.7%) or four (11.9%) high-risk factors. Increasing cumulative numbers of high-risk factors were associated with numerically shorter PFS and OS.Conclusion: Risk profiles should be carefully considered when planning clinical care.

Does the number of risk factors a person with advanced ovarian cancer have affect the likely success of their cancer treatment?What is already known on this topic? Studies have found that individual factors, such as disease stage, and whether any cancer cells remain after surgery are linked to earlier disease worsening and/or shorter survival after treatment in people with advanced ovarian cancer. These are known as 'risk factors'. However, few studies have looked at whether this link is stronger if a person has several of these risk factors.What does this study add? In this study, we looked at whether outcomes after treatment worsen as the number of risk factors increases. We found that patients with more high-risk factors saw a worsening of their cancer much sooner than those with a fewer number of risk factors. Also, patients with multiple risk factors did not live as long as patients with fewer risk factors.How might this study affect research, practice or policy? When selecting therapies, healthcare providers should consider the impact of patient risk factors on how effectively that treatment will treat their cancer. The number of high-risk factors may also make an important difference in clinical trials and, therefore, should be considered when comparing results from different clinical trials.

Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center.

PURPOSE: Breast cancer is a primary cause of cancer-related death among women worldwide. Neoadjuvant chemotherapy (NACT) is a cornerstone treatment for locally advanced, non-metastatic breast cancer. Achieving pathological complete response (pCR) is often used as a surrogate marker for long-term outcomes. This study examines the impact of obesity, defined by a body mass index (BMI) over 30 kg/m2, on achieving pCR in patients with early stage breast cancer (eBC) undergoing NACT. METHODS: A retrospective analysis was conducted on patients with eBC treated with NACT at the University of Tübingen. The primary objective was to assess the impact of obesity on achieving pCR. Logistic regression analysis was used to determine the association between pre-treatment BMI and pCR, adjusting for covariates such as age, tumor stage, grading, and chemotherapy intensity. RESULTS: The study included 325 patients, with 24% classified as obese. While the univariate logistic regression analysis showed no significant impact of obesity on the odds ratio of achieving pCR, the multivariate analysis, accounting for covariates, demonstrated that obese patients had a significantly higher likelihood of achieving pCR. CONCLUSION: In this retrospective study, obesity significantly affected the likelihood of achieving pCR in patients with eBC cancer undergoing NACT after adjusting for covariates. While obesity is a known risk factor for breast cancer development and progression, its impact on the efficacy of NACT in terms of achieving pCR was positive in our study. These findings contribute to the ongoing debate in the literature, though the retrospective design and potential uncontrolled factors should be considered.

Ultrasound-guided breast-conserving surgery compared to conventional breast-conserving surgery.

PURPOSE: The goal of breast-conserving surgery is to achieve negative tumor margins, since insufficient marginal distance is associated with more local and distant recurrences. This study investigates whether IOUS (intraoperative ultrasound) can reduce the re-resection rate compared to standard breast surgery, regardless of tumor biology and focality. MATERIALS AND METHODS: The present study is a monocentric, prospective, randomized, and non-blinded parallel group study conducted between 7/2015 and 2/2018. Patients with sonographically visible breast cancer were randomized into two study arms: 1) breast-conserving surgery with IOUS; 2) conventional arm. RESULTS: 364 patients were included in the study and underwent surgery. Tumor biology, size, and focality were equally distributed in both groups (p = 0.497). The study arms did not differ significantly in the proportion of preoperative wire markings (p= 0.084), specimen weight (p = 0.225), surgery duration (p = 0.849), and the proportion of shavings taken intraoperatively (p = 0.903). Positive margins were present in 16.6% of the cases in the IOUS arm and in 20.8% in the conventional arm (p = 0.347). Re-operation was necessary after intraoperative shavings in 14.4% of cases in the US arm and in 21.3% in the conventional arm (p = 0.100). CONCLUSION: Although the present study showed a clear difference in the rate of positive tumor margins with IOUS compared to conventional breast surgery without IOUS, this was not statistically significant in contrast to the current literature. This could be due to the high expertise of the breast surgeons, the precise wire marking, or the fact that the IOUS technique was not standardized.

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer.

Breast cancer remains a leading cause of cancer mortality in women globally. Despite advancements in systemic therapy, the risk of distant recurrence persists even after such treatment and may be linked to disseminated tumor cells (DTCs). Variability in molecular characteristics between primary tumors (PTs) and distant metastases underscores the need to comprehensively understand metastatic pathways. This retrospective study investigated discrepancies between HER2 expression in PTs and DTCs and their implications for survival outcomes in 201 early breast cancer (EBC) patients. We found a significant association between HER2 expression in PTs and DTCs when classifying tumors as HER2-high/low/negative. Patients whose HER2 status was discordant between PTs and DTCs exhibited worse distant disease-free survival than those with concordant status. Multivariate analysis confirmed the HER2 status of DTCs as an independent prognostic factor for distant DFS. These findings emphasize the importance of assessing HER2 expression in DTCs and its potential implications for tailored therapy strategies in EBC. Furthermore, prospective trials are needed to validate these findings and explore targeted therapies based on the molecular characteristics of DTCs.

Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome.

Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.

Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value.

BACKGROUND: Circulating tumour cells (CTCs) are mainly enriched based on the epithelial cell adhesion molecule (EpCAM). Although it was shown that an EpCAM low-expressing CTC fraction is not captured by such approaches, knowledge about its prognostic and predictive relevance and its relation to EpCAM-positive CTCs is lacking. METHODS: We developed an immunomagnetic assay to enrich CTCs from metastatic breast cancer patients EpCAM independently using antibodies against Trop-2 and CD-49f and characterised their EpCAM expression. DNA of single EpCAM high expressing and low expressing CTCs was analyzed regarding chromosomal aberrations and predictive mutations. Additionally, we compared CTC-enrichment on the CellSearch system using this antibody mix and the EpCAM based enrichment. RESULTS: Both antibodies acted synergistically in capturing CTCs. Patients with EpCAM high-expressing CTCs had a worse overall and progression-free survival. EpCAM high- and low-expressing CTCs presented similar chromosomal aberrations and mutations indicating a close evolutionary relationship. A sequential enrichment of CTCs from the EpCAM-depleted fraction yielded a population of CTCs not captured EpCAM dependently but harbouring predictive information. CONCLUSIONS: Our data indicate that EpCAM low-expressing CTCs could be used as a valuable tumour surrogate material-although they may be prognostically less relevant than EpCAM high-expressing CTCs-and have particular benefit if no CTCs are detected using EpCAM-dependent technologies.

Association between 21-gene-assay and detection of disseminated tumor cells in patients with early breast cancer: results from the IRMA trial.

PURPOSE: Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A secondary endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. METHODS: DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. RESULTS: Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p = 0.034). The odds for DTC-positivity increased with rising RS values (p = 0.047). CONCLUSION: We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing.

Return of individual genomic research results within the PRAEGNANT multicenter registry study.

PURPOSE: The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient's quality of life) using a questionnaire. METHODS: 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient's quality of life. RESULTS: 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% (N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures (N = 15) were covered by the patients' health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% (N = 17) the results influenced whether family members will be genetically tested. CONCLUSION: This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.

Treatment and survival of patients with malignant ovarian sex cord-stromal cell tumours: An analysis of the Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) study group CORSETT database.

BACKGROUND: Malignant sex cord-stromal cell tumours (SCST) account for only 7% of ovarian malignancies. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) study group has established a clinicopathological database to provide an overview of the current treatment strategies and survival of SCST patients and to identify research needs. METHODS: Twenty centres provided mixed retro- and prospective data of patients with tumour specimens and second-opinion pathology review treated between 2000 and 2014. Descriptive analyses of treatment strategies, Kaplan-Meier curves and cox regression analyses were conducted. RESULTS: Two hundred and sixty-two SCST patients were included. One hundred and ninety-one Granulosa-cell tumour (GCT) and 17 Sertoli-Leydig cell tumour (SLCT) patients were stage I disease (>80%). Forty four GCT (18.7%) and two (8.3%) SLCT patients received adjuvant systemic treatment. After a median observation time of 78.2 months, 46% of all SCST patients experienced disease recurrence, treated predominantly with secondary debulking surgery (> 90%). Advanced FIGO stage, lymph node involvement and intra-operative capsule rupture were associated with disease recurrence on univariate analysis (all p < 0.05). Median OS time was not reached. DISCUSSION: In this analysis of SCST patients, adjuvant chemotherapy was unable to prevent disease recurrence. Despite high recurrence rates, overall survival rates were excellent.

Evaluating ChatGPT as an adjunct for the multidisciplinary tumor board decision-making in primary breast cancer cases.

BACKGROUND: As the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer? MATERIAL AND METHODS: We performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated. RESULTS: Results showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy "hormonal treatment". CONCLUSIONS: Support of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.

Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients.

Disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer (BC) patients are putative precursors of metastatic disease, and their presence is associated with an adverse clinical outcome. To achieve the personalization of therapy on a clinical routine level, the characterization of DTCs and in vitro drug testing on DTCs are of great interest. Therefore, biobanking methods, as well as novel approaches to DTC isolation, need to be developed. In this study, we established a protocol for the biobanking of BM samples and evaluated a microfluidic-based separation system (Parsortix®) for the enrichment of cryopreserved DTCs. We were able to successfully isolate viable DTCs after the prior cryopreservation of BM samples. We calculated a significant increase of up to 90-fold in harvested DTCs with the proposed method compared to the current standard techniques, opening up new analysis possibilities for DTCs. Our advanced method further presents options for 3D DTC cultures, enabling the individualized testing of targeted therapies for BC patients. In conclusion, we present a novel approach for DTC enrichment, with possibilities for future clinical implications.

Targeting NKG2DL with Bispecific NKG2D-CD16 and NKG2D-CD3 Fusion Proteins on Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with a poor response rate to conventional systemic treatment and high relapse rates. Members of the natural killer group 2D ligand (NKG2DL) family are expressed on cancer cells but are typically absent from healthy tissues; thus, they are promising tumor antigens for novel immunotherapeutic approaches. We developed bispecific fusion proteins (BFPs) consisting of the NKG2D receptor domain targeting multiple NKG2DLs, fused to either anti-CD3 (NKG2D-CD3) or anti-CD16 (NKG2D-CD16) Fab fragments. First, we characterized the expression of the NKG2DLs (MICA, MICB, ULBP1-4) on TNBC cell lines and observed the highest surface expression for MICA and ULBP2. Targeting TNBC cells with NKG2D-CD3/CD16 efficiently activated both NK and T cells, leading to their degranulation and cytokine release and lysis of TNBC cells. Furthermore, PBMCs from TNBC patients currently undergoing chemotherapy showed significantly higher NK and T cell activation and tumor cell lysis when stimulated with NKG2D-CD3/CD16. In conclusions, BFPs activate and direct the NK and T cells of healthy and TNBC patients against TNBC cells, leading to efficient eradication of tumor cells. Therefore, NKG2D-based NK and T cell engagers could be a valuable addition to the treatment options for TNBC patients.

The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers.

The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2- early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2- breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2- eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2- breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2- eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.

The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C.

BACKGROUND: Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy. METHODS: Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models. RESULTS: AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89-1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80-1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86-1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77-1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3-4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology. CONCLUSION: For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.

Early dissemination seeds metastasis in breast cancer.

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation, but the mechanisms of early metastatic spread have not yet been addressed. Here, by studying metastasis in a HER2-driven mouse breast cancer model, we show that progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination.

Implementation of an Electronic Patient-Reported Outcome App for Health-Related Quality of Life in Breast Cancer Patients: Evaluation and Acceptability Analysis in a Two-Center Prospective Trial.

BACKGROUND: One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. OBJECTIVE: The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. METHODS: Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. RESULTS: Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app's evaluation parameters. CONCLUSIONS: The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.