Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.

Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I-III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy.

Predicting treatment outcome using kinome activity profiling in HER2+ breast cancer biopsies.

In this study, we measured the kinase activity profiles of 32 pre-treatment tumor biopsies of HER2-positive breast cancer patients. The aim of this study was to assess the prognostic potential of kinase activity levels, to identify potential mechanisms of resistance and to predict treatment success of HER2-targeted therapy combined with chemotherapy. Indeed, our system-wide kinase activity analysis allowed us to link kinase activity to treatment response.

Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade.

Tumor-infiltrating lymphocytes (TILs) have been associated with outcomes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and trastuzumab. However, it remains unclear if TILs could be a prognostic and/or predictive biomarker in the context of dual HER2-targeting treatment. In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial.

Deep (phospho)proteomics profiling of pre- treatment needle biopsies identifies signatures of treatment resistance in HER2 breast cancer.

Patients with early-stage HER2-overexpressing breast cancer struggle with treatment resistance in 20%-40% of cases. More information is needed to predict HER2 therapy response and resistance in vivo. In this study, we perform (phospho)proteomics analysis of pre-treatment HER2 needle biopsies of early-stage invasive breast cancer to identify molecular signatures predictive of treatment response to trastuzumab, pertuzumab, and chemotherapy.

BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer.

Background: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.

Tumour-educated platelets for breast cancer detection: biological and technical insights.

Background: Studies have shown that blood platelets contain tumour-specific mRNA profiles tumour-educated platelets (TEPs). Here, we aim to train a TEP-based breast cancer detection classifier.

Methods: Platelet mRNA was sequenced from 266 women with stage I-IV breast cancer and 212 female controls from 6 hospitals.

Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival.

Background: Pathologic complete response (pCR) rates in early stage HER2-positive breast cancer improved after pertuzumab was added to neoadjuvant treatment. However, survival benefit is less-well established and seems mostly limited to node-positive patients. We used national cancer registry data to compare outcomes of patients treated with and without pertuzumab.

The Way of the Future: Personalizing Treatment Plans Through Technology.

Advances in tissue analysis methods, image analysis, high-throughput molecular profiling, and computational tools increasingly allow us to capture and quantify patient-to patient variations that impact cancer risk, prognosis, and treatment response. Statistical models that integrate patient-specific information from multiple sources (e.g.

Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping.

Extracellular vesicles (EVs) are a potential source of disease-associated biomarkers for diagnosis. In breast cancer, comprehensive analyses of EVs could yield robust and reliable subtype-specific biomarkers that are still critically needed to improve diagnostic routines and clinical outcome. Here, we show that proteome profiles of EVs secreted by different breast cancer cell lines are highly indicative of their respective molecular subtypes, even more so than the proteome changes within the cancer cells.

Vitamin D and C-Reactive Protein: A Mendelian Randomization Study.

Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein.