Introduction: The persistence of circulating tumor cells (CTC) in breast cancer patients might be associated with stem cell like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, these cells also may undergo phenotypic changes, known as epithelial-mesenchymal transition (EMT), which allows them to travel to the site of metastasis formation without getting affected by conventional treatment. Here we evaluated 226 blood samples of 39 metastatic breast cancer patients during a follow-up of palliative chemo-, antibody – or hormonal therapy for the expression of the stem cell marker ALDH1 and markers for EMT and correlated these findings with the presence of CTC and response to therapy. Methods: 2 × 5 ml blood was analyzed for CTC with the AdnaTest BreastCancer (AdnaGen AG) for the detection of EpCAM, MUC-1 and HER2 transcripts. The recovered c-DNA was additionally multiplex tested for three EMT markers [Twist1, Akt2, PI3Kα] and separately for the tumor stem-cell markers ALDH1. The identification of EMT markers was considered positive if at least one marker was detected in the sample. Results: 97% of 30 healthy donor samples investigated were negative for EMT and 95% for ALDH1 transcripts. CTC were detected in 69/226 (31%) cancer samples. In the CTC (+) group, 62% were positive for at least one of the EMT markers and 69% for ALDH1, respectively. In the CTC (-) group the percentages were 7% and 14%, respectively. In non-responders, EMT and ALDH1 expression was found in 62% and 44% of patients, in responders the rates were 10% and 5%, respectively. Conclusions: Our data indicate that a major proportion of CTC of metastatic breast cancer patients shows EMT and tumor stem cell characteristics. Further studies are needed to prove whether these markers might serve as an indicator for therapy resistant tumor cell populations and, therefore, an inferior prognosis.

Background: In order to counteract fatigue, physical activity (PA) is recommended for all stages of cancer. However, only few advanced cancer patients (ACP) are physically active. Quantitative data with high numbers of ACP reporting barriers to PA are missing. This study aimed to identify barriers to PA in ACP with tiredness/weakness and investigate their motivation towards it. Methods: Outpatients with metastatic cancer receiving cancer care at a German Cancer Center reporting moderate/severe tiredness/weakness during self-assessment (MIDOS II) were enrolled. We assessed Fatigue-(FACF-F) and Depression (PHQ8) Scores, demographics, cancer-specific parameters, motivation for PA, physical, psychological and social barriers. Results: 141 of 440 eligible patients (32.0%) with different diagnoses agreed to participate. Patients frequently reported “I feel weakened due to my tumor therapy” (n = 108; 76.6%), physical symptoms (tiredness, weakness, dyspnea, joint-problems, pain, nausea [n = 107; 75.9%]) and fatigue (n = 99; 70.2%) as barriers to PA. However, no significant group differences regarding these barriers were found between physically active and inactive patients. Social barriers were rarely chosen. Motivated patients were 5.6 times more likely to be physically active (p < 0.001), also motivation turned out to be the strongest predictor for a physically active behavior (β = 1.044; p = 0.005). Motivated attitude towards PA was predicted by fatigue (β = − 2.301; p = 0.008), clinically relevant depression (β = − 1.390, p = 0.039), knowledge about PA and quality of life (QoL) (β = 0.929; p = 0.002), PA before diagnosis (β = 0.688; p = 0.005 and Interest in exercise program (β = 0.635; p = 0.008). Conclusion: “I feel weakened due to my tumor therapy” is the most reported barrier to PA among both, physically and inactive patients. Motivation for PA is the strongest predictor of performing PA. Interest in PA, knowledge about PA/QoL and PA before diagnosis are main predictors of a motivated attitude. Absence/presence of social barriers did not associate with motivation, fatigue and depression proved to be a negative predictor. Programs including information, motivational counseling and individualized training should be offered for ACP to overcome barriers and reduce fatigue. Trial registration: German Register of Clinical Trials DRKS00012514, registration date: 30.5.2017.

Exercise therapy is a common supportive strategy in curative cancer treatment with strong evidence regarding its positive effects on, for example, cancer-related fatigue, health- related quality of life, and physical function. In the field of advanced cancer patients, knowledge about exercise as a useful supportive strategy is missing. The aim of this systematic review was to evaluate the feasibility and safety of exercise interventions as well as its effects on lowering the symptom burden. We included randomized controlled trials and nonrandomized controlled trials with advanced cancer patients receiving any type of exercise intervention. After an extensive literature search (in accordance to PRIMSA guidelines) in PubMed, Cochrane Library, and SPORTDiscus, 14 studies including 940 participants with different cancer entities were eligible. The results indicated the safety of exercise. In total, 493 participants received exercise interventions, with nine adverse events and no severe adverse events. The median recruitment rate was 68.33%, and adherence to exercise intervention was 86%. Further research with a high-quality and larger sample size is needed to clarify the potential of exercise with advanced cancer patients. Different advanced cancer entities have distinguished symptoms, and future research should construct entities-specific trial populations to figure out the best supportive exercise interventions.

The expression of HER2, estrogen (ER) and progesterone (PR) receptor can change during the course of the disease in breast cancer (BC). Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. In this context, characterization of circulating tumor cells (CTCs) could be of relevance since metastatic tissue may be difficult to obtain for repeated analysis. Here we compared HER2/ER/PR expression profiles of primary tumors, metastases and CTCs. Ninety-six patients with metastatic BC from seven University BC Centers in Germany were enrolled in this study. Blood was obtained at the time of first diagnosis of metastatic disease or disease progression and analyzed for CTCs using the AdnaTest BreastCancer (QIAGEN Hannover GmbH, Germany) for the expression of EpCAM, MUC-1, HER2, ER and PR. HER2 expression on CTCs was additionally assessed by immunocytochemistry using the CellSearch® assay. The detection rate for CTCs using the AdnaTest was 43 % (36/84 patients) with the expression rates of 50 % for HER2 (18/36 patients), 19 % for ER (7/36 patients) and 8 % for PR (3/36 patients), respectively. Primary tumors and CTCs displayed a concordant HER2, ER and PR status in 59 % (p = 0.262), 39 % (p = 0.51) and 44 % (p = 0.62) of cases, respectively. For metastases and CTCs, the concordance values were 67 % for HER2 (p = 0.04), 43 % for ER (p = 0.16) and 46 % for PR (p = 0.6). Using the CellSearch® assay, the CTC-positivity rate was 53 % (42/79 patients) with HER2 expressed in 29 % (12/42) of the patients. No significant concordance (58 % and 53 %) was found when HER2 on CTCs was compared with HER2 on primary tumors (p = 0.24) and metastases (p = 0.34). Interestingly, primary tumors and metastases were highly concordant for HER2 (84 %, p = 1.13E-08), ER (90 %, p = 3.26E-10) and PR (83 %, p = 2.09E-09) and ER-and PR-positive metastases were significantly found to be of visceral origin (p = 0.03, p = 0.02). Here we demonstrate that the molecular detection of HER2 overexpression in CTC is predictive of the HER2 status on metastases. Detailed analysis of ER and PR expression rates in tissue samples and CTCs may provide useful information for making treatment decisions.

Cancer patients account for a large segment of the German healthcare system, with a 5-year prevalence of around 1.7 million persons. Advances in oncological treatment, now frequently performed on an outpatient basis, are granting many of these individuals a longer life span. At the same time, cancer patients often suffer disease-related symptoms and adverse effects from their tumor treatment, which may strongly impair their quality of life despite the improved techniques for management of side effects. This review is based on a selective literature search of the PubMed and Cochrane Library databases carried out in December 2019 and January 2020. Special attention was paid to guidelines, expert opinions, and recommendations from professional societies. Alongside decreased well-being, cancer patients often suffer from fatigue (70–100%), loss of appetite (6–53%), pain (30–80 %), and dyspnea (10–70%). The prevalence and severity of the symptoms varies depending on the tumor entity and the patient’s sex. A meta-analysis showed that besides causal treatment, physical activity achieves moderately strong effects in tumor-associated fatigue syndrome (Cohen’s d = 0.30 [0.25; 0.36]). The WHO recommends early use of opioids in tumor-associated pain. A meta-analysis of randomized trials described symptom relief by means of opioids also in dyspnea (standardized mean difference: -0.32 [-0.53; -0.10]). Increasingly, guidelines are recommending regular palliative medical symptom screening. Regular documentation of symptoms in outpatients offers the opportunity for targeted management of symptoms during treatment with the involvement of various disciplines such as palliative medicine, exercise therapy, and psychotherapy.

The aim of this study was to analyze individual changes in cancer patients’ mental health before and after the COVID-19 outbreak, and to explore predictors of mental health impairment. Over a two-week period (16–30 March 2020), 150 cancer patients in Germany participated in this study. Validated instruments assessed demographic and medical data, depression and anxiety symptoms (PHQ-2, GAD-2), distress (DT), and health status (EQ-5D-3L). All instruments were adapted to measure the individual mental health before the COVID-19 outbreak. COVID-19-related fear, trust in governmental actions to face COVID-19, and the subjective level of information regarding COVID-19 were measured. Cancer patients showed a significant increase in depression and anxiety symptoms and distress, while health status deteriorated since the COVID-19 outbreak. Increased depression and generalized anxiety symptoms were predicted by COVID-19-related fear. Trust in governmental actions to face COVID-19 and COVID-19-related fear predicted increases in distress. Higher subjective levels of information predicted less increasing anxiety symptoms and distress. Present data suggests that cancer patients experienced a significant increase in mental health burden since the COVID-19 outbreak. Observed predictors of mental health impairment and protective factors should be addressed, and appropriate interventions established, to maintain mental health of cancer patients during the pandemic.