App-based support for breast cancer patients to reduce psychological distress during therapy and survivorship - a multicentric randomized controlled trial.

Introduction: The negative impact of unmanaged psychological distress on quality of life and outcome in breast cancer survivors has been demonstrated. Fortunately, studies indicate that distress can effectively be addressed and even prevented using evidence-based interventions. In Germany prescription-based mobile health apps, known as DiGAs (digital health applications), that are fully reimbursed by health insurances, were introduced in 2020. In this study, the effectiveness of an approved breast cancer DiGA was investigated: The personalized coaching app PINK! Coach supports and accompanies breast cancer patients during therapy and follow-up. Methods: PINK! Coach was specifically designed for breast cancer (BC) patients from the day of diagnosis to the time of Follow-up (aftercare). The app offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT (DRKS00028699) was performed with n = 434 patients recruited in 7 German breast cancer centers from September 2022 until January 2023. Patients with BC were included independent of their stage of diseases, type of therapy and molecular characteristics of the tumor. Patients were randomized into one of two groups: The intervention group got access to PINK! over 12 weeks; the control group served as a waiting-list comparison to "standard of care." The primary endpoint was psychological distress objectified by means of Patient Health Questionnaire-9 (PHQ-9). Subgroups were defined to investigate the app's effect on several patient groups such as MBC vs. EBC patients, patients on therapy vs. in aftercare, patients who received a chemotherapy vs. patients who did not. Results: Efficacy analysis of the primary endpoint revealed a significant reduction in psychological distress (least squares estimate -1.62, 95% confidence interval [1.03; 2.21]; p<0.001) among intervention group patients from baseline to T3 vs, control group. Subgroup analysis also suggested improvements across all clinical situations. Conclusion: Patients with breast cancer suffer from psychological problems including anxiety and depression during and after therapy. Personalized, supportive care with the app PINK! Coach turned out as a promising opportunity to significantly improve psychological distress in a convenient, accessible, and low-threshold manner for breast cancer patients independent of their stage of disease (EBC/MBC), therapy phase (aftercare or therapy) or therapy itself (chemotherapy/other therapy options). The app is routinely available in Germany as a DiGA. Clinical Trial Registration: DRKS Trial Registry (DRKS00028699).

App-Based Lifestyle Intervention (PINK! Coach) in Breast Cancer Patients-A Real-World-Data Analysis.

INTRODUCTION: Overweight and a lack of physical activity not only increase the risk of recurrence in breast cancer patients but also negatively impact overall and long-term survival, as well as quality of life. The results presented here are the first real-world data from the DiGA PINK! Coach examining the physical activity and BMI of app users. Based on the literature, an approximate weight gain of 10% over 6 months and a decrease in physical activity can be expected. The purpose of this study is to retrospectively investigate the effects of the PINK! Coach in a real-world setting on patients' BMI and physical activity level during acute therapies. such as chemotherapy (CHT) and antihormone therapy (AHT). MATERIAL AND METHODS: The PINK! Coach app accompanies breast cancer patients during and after acute therapy to bring about a sustainable lifestyle change. The patients are encouraged to establish a healthy diet, become physically active, and make informed decisions. In this study, real-world data from the app were analyzed over 6 months from baseline to T1 (after 12 weeks) and T2 (after 24 weeks). The patients were under acute therapy or in follow-up care receiving either CHT or AHT. RESULTS: The analyzed data indicate that all patients were able to maintain a consistent BMI over 6 months independent of pre-defined subgroups such as AHT, CHT, or BMI subgroups. In the subgroup of patients undergoing AHT, overweight patients were even able to significantly reduce their BMI by 1-score-point over 6 months (p < 0.01). The subgroup of patients undergoing CHT also showed an significant overall reduction in BMI (p = 0.01). All patients were also able to significantly increase their daily step count as well as their physical activity minutes per day. After the first 12 weeks, 41.4% of patients experienced weight gain, 33.4% were able to maintain their weight, and 24.2% reduced their weight. CONCLUSION: The presented data provides intriguing insights into the users of the PINK! Coach app and the impact of this usage in regards to BMI and physical activity. At the current time, there are only a few effective concepts for encouraging all breast cancer patients to engage in moderate physical activity and reduce body weight. Often, these concepts apply to selected patient groups. The data presented here include all age groups, tumor stages, and therapies, providing an initial insight into a comprehensive approach. Data over an even longer period would be one way to better contextualize the results in current research.

App-Based Lifestyle Coaching (PINK!) Accompanying Breast Cancer Patients and Survivors to Reduce Psychological Distress and Fatigue and Improve Physical Activity: A Feasibility Pilot Study.

Introduction: This pilot study aimed to investigate the effects of using an app-based certified medical product named PINK! on breast cancer patients and survivors. The objectives were to measure psychological distress, physical activity, and therapy-related fatigue of patients using PINK! to identify trends and develop a study design for a subsequent multicentric proof of efficacy RCT. Materials and Methods: PINK! offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT was performed with n = 60 patients in 2021 at Comprehensive Cancer Center Munich. Patients with BC were included independent of the stage of diseases. The intervention group got access to PINK! over 12 weeks. Control group served as a waiting-list comparison to "standard of care." Results: Primary efficacy variable analysis revealed a relative average decrease of 32.9% in psychological distress, which corresponds to a statistically significant reduction (p < 0.001) within 12 weeks compared to the control group. Linear regressions within usage groups showed a correlation of high app usage and a reduction of psychological distress. Fatigue data presented a statistically significant antifatigue efficacy (p < 0.001) and physical activity increased by 63.9%. Conclusion: App-based supportive care offers a promising, low-threshold, and cost-efficient opportunity to improve psychological well-being, quality of life, fatigue, and physical activity. More research is needed to implement eHealth solutions in clinical cancer care.

Beta-hCG/LH receptor (b-HCG/LH-R) expression is increased in invasive versus preinvasive breast cancer: implications for breast carcinogenesis?

INTRODUCTION: The role of the b-HCG/LH/LH-R system in breast cancer is conflicting. Whereas some reports suggest a protective effect of b-HCG on breast epithelium, vitro studies implicate a role of b-HCG/LH-R in the development and growth of breast tumors. MATERIAL AND METHODS: In order to further investigate a possible involvement of b-HCG/LH-R in breast carcinogenesis, immunofluorescence analyses of b-HCG/LH-R expression was performed on 70 preinvasive and adjacent invasive breast cancer specimen using tissue microarrays (TMAs). RESULTS: In 37 preinvasive samples available for further analysis, b-HCG/LH-R was found in 8/37 samples (21.6%; weak, intermediate and strong staining in 4/37 (10.8%), 2/37 (5.4%) and 2/37 (5.4%). In contrast, b-HCG/LH-R expression was observed in 19/27 (70.4%) adjacent invasive specimen with weak, moderate and strong immunostaining in 10/27 (37.0%), 6/27 (22.2%) and 3/27 (11.1%), respectively. This was statistically significant when compared to preinvasive components (P = 0.001, Chi Square Test). CONCLUSIONS: Based on the observation that b-HCG/LH-R was found to be selectively upregulated in invasive tumor components, we suggest that under certain circumstances, sensitivity of ductal cells to hormones that target b-HCG/LH-R could favour mammary carcinogenesis.

Androgen receptor expression in ductal carcinoma in situ of the breast: not a helpful marker for classification such as estrogen receptor alpha and progesterone receptor.

Androgen receptor (AR) is known to be expressed in approximately 70 to 90% of invasive breast cancers, but there are still conflicting data in terms of AR expression in ductal carcinoma in situ (DCIS). The aim of this study was to evaluate AR expression in DCIS and to compare these results with nuclear grading and with other common endocrine-related markers. On this basis the authors performed immunohistochemical staining for estrogen receptor (ER)-alpha and ER-beta, progesterone receptor (PR), pS2, her-2/neu, and AR in 59 cases of DCIS (24 low grade, 5 intermediate grade, 30 high grade). They found a strong correlation of expression of ER-alpha (P=0.003), PR (P<0.0001), and nuclear grading. For AR expression, 44.1% of all DCIS were positive, but there was no correlation between nuclear grading (P=0.535) and the expression of the other factors. The authors conclude that AR expression in DCIS is not correlated with nuclear grading and with the expression of other known endocrine-related markers such as ER-alpha and -beta, PR, pS2, and her-2/neu. The immunohistochemical assessment of AR status, therefore, may not help in providing a more objective way of classifying DCIS.

Estrogen receptor alpha and beta, progesterone receptor, pS2 and HER-2/neu expression delineate different subgroups in ductal carcinoma in situ of the breast.

Antiestrogen therapy of ductal carcinoma in situ (DCIS) has become a more common option in reducing risk of developing invasive cancer. Previously, estrogen receptor alpha (ER-alpha) was evaluated as the only predictive factor. Immunohistochemical staining was performed for ER-alpha, estrogen receptor ER-beta, progesterone receptor (PR), pS2 and her-2/neu in 59 cases of ductal carcinoma in situ (DCIS). We observed a positive correlation between the expression of ER-alpha (p=0.003), PR (p<0.001) and histopathological grading. Of the DCIS, 61.5% of ER-beta positive (p=0.046) and 35.5% of PR positive samples showed a coexpression with pS2, whereas 72.1% of pS2 negative DCIS were also negative for ER-beta and 92.9% of PR negative DCIS were negative for pS2 (p=0.012). In contrast, 50.0% of her-2/neu negative DCIS expressed ER-beta receptor (p=0.052). We propose that there are subpopulations of DCIS which can be described by distinct endocrine-associated expression patterns.