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Purpose: The reliable detection of tumor-infiltrated axillary lymph nodes for breast cancer [BC] patients plays a decisive role in further therapy. We aimed to find out whether cross-sectional imaging techniques could improve sensitivity for pretherapeutic axillary staging in nodal-positive BC patients compared to conventional imaging such as mammography and sonography. Methods: Data for breast cancer patients with tumor-infiltrated axillary lymph nodes having received surgery between 2014 and 2020 were included in this study. All examinations (sonography, mammography, computed tomography [CT] and magnetic resonance imaging [MRI]) were interpreted by board-certified specialists in radiology. The sensitivity of different imaging modalities was calculated, and binary logistic regression analyses were performed to detect variables influencing the detection of positive lymph nodes. Results: All included 382 breast cancer patients had received conventional imaging, while 52.61% of the patients had received cross-sectional imaging. The sensitivity of the combination of all imaging modalities was 68.89%. The combination of MRI and CT showed 63.83% and the combination of sonography and mammography showed 36.11% sensitivity. Conclusion: We could demonstrate that cross-sectional imaging can improve the sensitivity of the detection of tumor-infiltrated axillary lymph nodes in breast cancer patients. Only the safe detection of these lymph nodes at the time of diagnosis enables the evaluation of the response to neoadjuvant therapy, thereby allowing access to prognosis and improving new post-neoadjuvant therapies. [ABSTRACT FROM AUTHOR]

Purpose: An increasing incidence of breast cancer can be observed worldwide. Since a delay of therapy can have a negative impact on prognosis, timely cancer care is an important quality indicator. By receiving treatment at a certified breast cancer center, the patient has the best chance of treatment in accordance with guidelines and the best prognosis. The identification of risk factors for a delay of therapy is of central importance and should be the basis for a continuous optimization of treatment at breast cancer centers. Methods: This retrospective study included women with breast cancer (primary diagnosis, relapse, or secondary malignancy) at the University Hospital Würzburg in 2019 and 2020. Data were retrieved from patients' records. Correlations and regression analyses were performed to detect potential risk factors for treatment delay. Results: Patients who received the histological confirmation of breast cancer at an external institution experienced a later therapy start than those patients who received the histological confirmation at the University Hospital Würzburg itself. (35.7 vs. 32.2 days). The interval between histological confirmation and the first consultation at the University Hospital Würzburg correlated statistically significant with age, distress and distance to the hospital. Conclusion: Patients with an in-house diagnosis of breast cancer are treated more quickly than those whose diagnosis was confirmed in an external institution. We identified factors such as increased age, greater distance to the hospital as well as increased distress to prolong the time until start of oncological treatment. Intensified patient care should be offered to these subgroups. [ABSTRACT FROM AUTHOR]

As a result of the cancer diagnosis and the mostly multimodal, stressful therapy, psychological distress is a common symptom in breast cancer patients. As part of this prospective study, 1400 patients who were admitted to the hospital for oncological rehabilitation were screened for distress and somatic, therapy-induced secondary disorders. Mean distress in the screened population was 5.6 ± 2.56 (range 0–10). In 942 cases (67.3%) a significant distress score (≥ 5) was detected and in 587 cases (41.9%) very high levels of distress (≥ 7) was observed. Psychological distress significantly correlated with younger age, presence of triple negative breast cancer (TNBC), tumor recurrence and metastasis, and inability to work. Treatment-induced side effects such as lymphedema, CIPN or extensive tumor resection (mastectomy) showed a (not significant) trend for higher distress. The high incidence of distress underscores the importance of psycho-oncological therapy offers and the great importance of occupational measures during oncological rehabilitation such as the importance of a successful return to work for a better quality of life in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: This study examined the relationship between social service counseling (SSC) and financial and role functioning problems in primary breast cancer (BC) patients over a 5-year observation period. Methods: In the multicenter prospective study, patients were approached before surgery (t1), before initiation of adjuvant treatment (t2), after therapy completion (t3), and 5 years after surgery (t4). We examined the proportion of BC survivors who had financial and role functioning problems and the proportion who were employed at t4. We examined how frequently patients were informed about, offered, or used SSC, and we used multivariate logistic regression analyses to examine the relationship between this and financial and role functioning problem prevalence. Results: Of the 456 BC survivors, 33% had financial problems and 22% reported role functioning problems at t4. There was no evidence that women with increased financial problems were informed about SSC more often than those without (OR 1.1, p = 0.84) or that they used SSC more often (OR 1.3, p = 0.25). However, women with role functioning problems were informed about SSC significantly more often (OR 1.7, p = 0.02) and attended counseling significantly more often (OR 1.6, p = 0.03). Among participants aged < 65 years at t4 (n = 255), 70% were employed. Patients who had received SSC were more likely to be employed at t4 than patients who did not (OR 1.9, p = 0.04). Conclusion: These findings underline the importance of SSC for BC patients with role functioning issues. They indicate that individuals who use SSC are more likely to be employed later on than individuals who do not. [ABSTRACT FROM AUTHOR]

Introduction: Male breast cancer (MBC) is a rare malignancy that accounts for less than 1% of all cancers in men and less than 1% of all breast cancers worldwide. Understandably, due to the low incidence of this rare cancer, there is a lack of prospective clinical data. The aim of this retrospective study was the analysis of therapy-induced toxicities as well as the assessment of psychological distress in the affected men during oncological inpatient rehabilitation. Methods: Fifty-one MBC patients were evaluated for the presence of treatment-induced side effects, toxicities, and psychological distress (using German version of the 11-stage NCCN distress thermometer; cut-off ≥5) during oncological indoor rehabilitation. The collected data were checked for correlation with sociodemographic and clinical factors (SPSS 22). Results: The mean age was 62.0 ± 10.6 years, in 96% a hormone-dependent breast tumor (ER+), and in over 75%, overweight or obesity (BMI >25/>30) was diagnosed. Most reported side effects included weakness/fatigue (74.5%), arthralgia after surgery/chemotherapy (43.1%), chemotherapy-induced polyneuropathy (36.3%), and/or lymphedema (13.7%). Psychological distress was detected in 24 cases (47.0%; ≥5), in 13 cases even with significantly high levels (25.5%; ≥7). There was no correlation between psychological distress and clinical factors such as age, performed treatment (e.g., chemotherapy), or therapy-induced side effects (e.g., lymphedema) in our small collective. Conclusions: Psychological distress and somatic side effects are common in MBC. These data demonstrate the importance of routine screening for psychological distress and the high need for psycho-oncological therapy (regardless of gender) in multimodal oncological rehabilitation. [ABSTRACT FROM AUTHOR]

Simple Summary: Anti-hormonal therapie regimes are well established in oncological treatments in breast cancer. In contrast there is limited knowledge of their effects on metastatic brain metastases in advanced breast cancer and their ability to cross the blood brain-barrier. In this review, we point out the usual antihormonal therapy options in the primary disease, but also in metastatic breast cancer. In addition, we explain the epidemiological facts of brain metastases, as well as the basics of the blood-brain barrier and how this is overcome by metastase. Last but not least, we deal with the known anti-hormonal therapy options and present clinical studies on their intracerebral effect, as well as the known basics of their blood-brain barrier penetration. Not all common anti-hormonal therapeutics are able to penetrate the CNS. It is therefore important for the treating oncologists to use substances that have been proven to cross the BBB, despite the limited data available. Aromataseinhibitors, especially letrozole, probably also tamoxifen, everolimus and CDK4/6 inhibitors, especially abemaciclib, appear to act intracerebrally by overcoming the blood-brain barrier. Nevertheless, further data must be obtained in basic research, but also health care research in relation to patients with brain metastases. The molecular receptor status of breast cancer has implications for prognosis and long-term metastasis. Although metastatic luminal B-like, hormone-receptor-positive, HER2−negative, breast cancer causes brain metastases less frequently than other subtypes, though tumor metastases in the brain are increasingly being detected of this patient group. Despite the many years of tried and tested use of a wide variety of anti-hormonal therapeutic agents, there is insufficient data on their intracerebral effectiveness and their ability to cross the blood-brain barrier. In this review, we therefore summarize the current state of knowledge on anti-hormonal therapy and its intracerebral impact and effects on the blood-brain barrier in breast cancer. [ABSTRACT FROM AUTHOR]

Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. In a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P =.72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P =.68). Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events. • Dose-response analysis on cardiac late effects in irradiated breast cancer patients. • Nested case-control study with individual retrospective heart dosimetry. • Included 494 cases and 988 controls treated in 1998–2008 in Germany. • No association for cardiac late effects of 3D-conformal radiotherapy observed. • No association for the complete heart and left anterior heart wall observed. [ABSTRACT FROM AUTHOR]

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use. [ABSTRACT FROM AUTHOR]

Background: The majority of breast cancer patients are severely psychologically affected by breast cancer diagnosis and subsequent therapeutic procedures. The COVID-19 pandemic and associated restrictions on public life have additionally caused significant psychological distress for much of the population. It is therefore plausible that breast cancer patients might be particularly susceptible to the additional psychological stress caused by the pandemic, increasing suffering. In this study we therefore aimed to assess the level of psychological distress currently experienced by a defined group of breast cancer patients in our breast cancer centre, compared to distress levels pre-COVID-19 pandemic.Methods: Female breast cancer patients of all ages receiving either adjuvant, neoadjuvant, or palliative therapies were recruited for the study. All patients were screened for current or previous COVID-19 infection. The participants completed a self-designed COVID-19 pandemic questionnaire, the Stress and Coping Inventory (SCI), the National Comprehensive Cancer Network® (NCCN®) Distress Thermometer (DT), the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30, and the BR23.Results: Eighty-two breast cancer patients were included. Therapy status and social demographic factors did not have a significant effect on the distress caused by the COVID-19 pandemic. The results of the DT pre and during COVID-19 pandemic did not differ significantly. Using the self-designed COVID-19 pandemic questionnaire, we detected three distinct subgroups demonstrating different levels of concerns in relation to SARS-CoV-2. The subgroup with the highest levels of concern reported significantly decreased life quality, related parameters and symptoms.Conclusions: This monocentric study demonstrated that the COVID-19 pandemic significantly affected psychological health in a subpopulation of breast cancer patients. The application of a self-created "COVID-19 pandemic questionnaire" could potentially be used to help identify breast cancer patients who are susceptible to increased psychological distress due to the COVID-19 pandemic, and therefore may need additional intensive psychological support.Trial Registration: DRKS-ID: DRKS00022507 . [ABSTRACT FROM AUTHOR]

Background: In order to offer optimal treatment approaches based on available evidence, the Commission Breast of the Working Group Gynecologic Oncology (AGO) of the German Cancer Society developed therapy algorithms for eight complex treatment situations in primary and advanced breast cancer. Summary: Therapy algorithms for the following complex treatment situations are outlined in this paper: (neo)adjuvant therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer; axillary surgery and neoadjuvant chemotherapy; adjuvant endocrine therapy in premenopausal patients; adjuvant endocrine therapy in postmenopausal patients; hormone receptor (HR)-positive/HER2-negative metastatic breast cancer: strategies; HR-positive/HER2-negative metastatic breast cancer: endocrine-based first-line treatment; HER2-positive metastatic breast cancer: first to third-line; metastatic triple-negative breast cancer. Key Messages: The therapy options shown in these algorithms are based on the current AGO recommendations updated in January 2020 but cannot represent all evidence-based treatment options. Prior therapies, performance status, comorbidities, patient preference, etc. must be taken into account for the actual treatment choice. Therefore, in individual cases, other evidence-based treatment options not listed here may also be appropriate and justified. [ABSTRACT FROM AUTHOR]

Background: The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions: (1) Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN? (2) Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN? (3) In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed?Methods: A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines.Results: 2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy.Conclusion: The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients. [ABSTRACT FROM AUTHOR]

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2 mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The BRENDA-Score provides an easy to use tool for clinicians to estimate the risk of recurrence in primary breast cancer. The algorithm has been validated via a second independent database and provides five recurrence risk groups. This grouping helps clinicians to encourage high risk patients to undergo the recommended treatment. Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival. [ABSTRACT FROM AUTHOR]