An early economic evaluation of active surveillance for low-risk ductal carcinoma .

Perform early economic evaluation comparing active surveillance (AS) to surgery for women with low-risk ductal carcinoma , a precursor of invasive breast cancer. A 10-year incremental costs (€) and quality-adjusted life years (QALYs) were compared between a simulated cohort of women undergoing breast conserving surgery ± radiotherapy, and a cohort with a low-risk subgroup undergoing AS using a semi-Markov model. Scenario and headroom analyses evaluated a better-performing biomarker to select low-risk women for AS.

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.

Ductal carcinoma in situ develops within clonal fields of mutant cells in morphologically normal ducts.

Mutations are abundantly present in tissues of healthy individuals, including the breast epithelium. Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field of mutant cells that is predisposed towards lesion formation. To study the clonal and spatial relationships between morphologically normal breast epithelium adjacent to pre-cancerous lesions, we developed a three-dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival, formalin-fixed breast tissue with the non-obligate breast cancer precursor ductal carcinoma in situ (DCIS).

Application of deep learning on mammographies to discriminate between low and high-risk DCIS for patient participation in active surveillance trials.

Background: Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S.

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population.

Purpose: To assess the effects of contemporary treatment of ductal carcinoma in situ (DCIS) on the risk of developing an ipsilateral invasive breast cancer (iIBC) in the Dutch female population.

Methods: Clinical data was obtained from the Netherlands Cancer Registry (NCR), a nationwide registry of all primary malignancies in the Netherlands integrated with the data from PALGA, the Dutch nationwide network and registry of histo- and cytopathology in the Netherlands, on all women in the Netherlands treated for primary DCIS from 2005 to 2015, resulting in a population-based cohort of 14.419 women.

PROACTING: predicting pathological complete response to neoadjuvant chemotherapy in breast cancer from routine diagnostic histopathology biopsies with deep learning.

Background: Invasive breast cancer patients are increasingly being treated with neoadjuvant chemotherapy; however, only a fraction of the patients respond to it completely. To prevent overtreatment, there is an urgent need for biomarkers to predict treatment response before administering the therapy.

Methods: In this retrospective study, we developed hypothesis-driven interpretable biomarkers based on deep learning, to predict the pathological complete response (pCR, i.

Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.

Objective: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer.

Design: Multinational, pooled cohort study.

Setting: Four large international cohorts.

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.

Characterization of the Tumor Microenvironment of De Novo Oligometastatic Breast Cancer in a Nationwide Cohort.

Purpose: Oligometastatic breast cancer (OMBC) has a more favorable outcome than widespread metastatic breast cancer. Some patients with OMBC achieve long-term remission if treated with multimodality therapy, including systemic and locally ablative therapies. However, not all patients with OMBC benefit from such treatment, while all experience toxicity.

High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial.

Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI).

Archival single-cell genomics reveals persistent subclones during DCIS progression.

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials.

Microcalcification crystallography as a potential marker of DCIS recurrence.

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored.

Immune landscape of breast tumors with low and intermediate estrogen receptor expression.

Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB treatment in the context of clinical trials.

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.

Learning to distinguish progressive and non-progressive ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a non-invasive breast neoplasia that accounts for 25% of all screen-detected breast cancers diagnosed annually. Neoplastic cells in DCIS are confined to the ductal system of the breast, although they can escape and progress to invasive breast cancer in a subset of patients. A key concern of DCIS is overtreatment, as most patients screened for DCIS and in whom DCIS is diagnosed will not go on to exhibit symptoms or die of breast cancer, even if left untreated.

Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy-Resistant Early Breast Cancers.

Purpose: To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)-resistant triple-negative breast cancer (TNBC) and ER+HER2- breast cancer disease.

Experimental Design: Following pathology review, 153 patients were identified as having residual cancer burden (RCB) II/III disease (TNBC n = 80; ER+HER2-n = 73). Baseline pre-NAC samples were available for evaluation for 32 of 80 TNBC and 36 of 73 ER+HER2- cases.

Comprehensive multiplexed immune profiling of the ductal carcinoma in situ immune microenvironment regarding subsequent ipsilateral invasive breast cancer risk.

Background: Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS.

Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases.

Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests.

Germline BRCA1/2 mutation status is predictive for response to Poly-[ADP-Ribose]-Polymerase (PARP) inhibitors in breast cancer (BC) patients. However, non-germline BRCA1/2 mutated and homologous recombination repair deficient (HRD) tumors are likely also PARP-inhibitor sensitive. Clinical validity and utility of various HRD biomarkers are under investigation.