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Breast cancer is the most common malignancy in women worldwide and a highly heterogeneous disease. Four different subtypes are described that differ in the expression of hormone receptors as well as the growth factor receptor HER2. Treatment modalities and survival rate depend on the subtype of breast cancer. However, it is still not clear which patients benefit from immunotherapeutic approaches such as checkpoint blockade. Thus, we aimed to decipher the immune cell signature of the different breast cancer subtypes based on high-dimensional flow cytometry followed by unbiased approaches. Here, we show that the frequency of NK cells is reduced in Luminal A and B as well as triple negative breast cancer and that the phenotype of residual NK cells is changed toward regulatory CD11b−CD16− NK cells. Further, we found higher frequencies of PD-1+ CD4+ and CD8+ T cells in triple negative breast cancer. Moreover, while Luminal A-type breast cancer was enriched for CD14+ cDC2 (named type 3 DC (DC3)), CD14− cDC2 (named DC2) were more frequent in triple negative breast cancer. In contrast, HER2-enriched breast cancer did not show major alterations in the composition of the immune cell compartment in the tumor microenvironment. These findings suggest that patients with Luminal A- and B-type as well as triple negative breast cancer might benefit from immunotherapeutic approaches targeting NK cells.

Abstract 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.

Purpose: Broader clinical adoption of breast magnetic resonance imaging (MRI) faces challenges such as limited availability and high procedural costs. Low-field technology has shown promise in addressing these challenges. We report our initial experience using a next-generation scanner for low-field breast MRI at 0.55T., Methods: This initial cases series was part of an institutional review board-approved prospective study using a 0.55T scanner (MAGNETOM Free.Max, Siemens Healthcare, Erlangen/Germany: height < 2 m, weight < 3.2 tons, no quench pipe) equipped with a seven-channel breast coil (Noras, Höchberg/Germany). A multiparametric breast MRI protocol consisting of dynamic T1-weighted, T2-weighted, and diffusion-weighted sequences was optimized for 0.55T. Two radiologists with 12 and 20 years of experience in breast MRI evaluated the examinations., Results: Twelve participants (mean age: 55.3 years, range: 36-78 years) were examined. The image quality was diagnostic in all examinations and not impaired by relevant artifacts. Typical imaging phenotypes were visualized. The scan time for a complete, non-abbreviated breast MRI protocol ranged from 10:30 to 18:40 min., Conclusion: This initial case series suggests that low-field breast MRI is feasible at diagnostic image quality within an acceptable examination time., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Dietzel: no competing interest, S. Ohlmeyer: no competing interest, F. Laun: no competing interest, S. Bickelhaupt: no competing interest, R. Heiss and M. Uder: Member of speakers bureau of Siemens Healthineers., (Copyright © 2024. Published by Elsevier B.V.)