Publications by authors named "Wildiers H"

Purpose: To investigate the clinical behavior of breast cancer in young carriers according to the specific gene () and the association of the timing of genetic testing (before at diagnosis) with prognosis.

Methods: This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in or , who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306).

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Chemotherapy combined with immune checkpoint blockade has shown clinical activity in breast cancer. Response, however, occurs in only a low proportion of patients. How the immune landscape of the tumor determines the immune and clinical responses to chemoimmunotherapy is not well understood.

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Background: Breast cancer is the most common malignancy in women and the leading cause of cancer-related death. Although most early-stage patients are cured, 20% to 30% develop metastases, significantly reducing survival rates. Recent research highlights the role of iron in cancer progression, although its full impact on breast cancer metastasis is not yet fully understood.

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Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment landscape for a wide variety of malignancies. Older adults represent a large and rapidly growing demographic, among whom ICIs are widely prescribed. Management of ICI-associated toxicity among older adults, particularly in the presence of frailty and comorbidity, poses unique challenges.

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Background: The adipose tissue may serve as a source of energy supporting cancer growth and metastasis. Our understanding of the adipocytes which compose the adipose tissue in different anatomical locations of the body as well as potential microscopic tumor infiltration in patients with metastatic breast cancer remains limited. This study therefore investigates regional variations in adipocyte size and adipose tissue tumor infiltration in patients with metastatic breast cancer.

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The immune landscape of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2- mBC), the most common subtype of BC, remains understudied. This is mainly because of reduced sample acquisition opportunities from metastases as compared with primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our post-mortem tissue donation program UZ/KU Leuven Post-mortem Tissue Donation program to Enhance Research (NCT04531696).

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Phyllodes tumors (PTs) are rare breast tumors showing overlapping features with fibroadenomas (FAs). Diagnosis on small biopsies is challenging. New diagnostic markers are needed.

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The impact of aging on the immune landscape of luminal breast cancer (Lum-BC) is poorly characterized. Understanding the age-related dynamics of immune editing in Lum-BC is anticipated to improve the therapeutic benefit of immunotherapy in older patients. To this end, here we applied the 'multiple iterative labeling by antibody neo-deposition' (MILAN) technique, a spatially resolved single-cell multiplex immunohistochemistry method.

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Article Synopsis
  • Primary and acquired endocrine resistance complicates treatment for hormone receptor positive breast cancer, often due to mutations in estrogen receptor 1 (ESR1) that cause estrogen-independent activation.
  • Selective estrogen receptor degraders (SERDs) are a new class of drugs that can degrade the ESR1 receptor, showing promise against this resistance, particularly in oral formulations that are more potent than the original intramuscular drug, fulvestrant.
  • Clinical trials, like the EMERALD trial for elacestrant and SERENA-2 for camizestrant, showed improved progression-free survival (PFS), particularly after prior treatments, while other SERDs like giredestrant and amcenestrant did not demonstrate this benefit
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Background: Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.

Methods: We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer.

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Article Synopsis
  • The DESTINY-Breast12 study is the largest prospective trial examining the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer, including those with brain metastases (BMs).
  • In this study, T-DXd showed promising results, with a 12-month progression-free survival (PFS) of 61.6% for patients with BMs and an objective response rate (ORR) of 62.7% for those without BMs.
  • Adverse events were observed in both cohorts, with 51% of patients with BMs and 49% of those without experiencing grade 3 or higher side effects, indicating the need for careful monitoring
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Objectives: The study was undertaken to assess the association between certification and volume of breast centres on the one hand and survival on the other in patients with invasive breast cancer (IBC).

Methods: The study comprises a cohort of 46,035 patients diagnosed with IBC between 2014 and 2018, selected from the nation-wide Belgian Cancer Registry (BCR) database, which was linked with health insurance, hospital discharge and vital status data. Overall and relative survival probabilities were obtained with Kaplan-Meier method and an actuarial approach based on Ederer II, respectively.

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Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival.

Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy.

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Purpose: To investigate the impact of adding digital breast tomosynthesis (DBT) to full field digital mammography (FFDM) in screening asymptomatic women with an elevated breast cancer life time risk (BCLTR) but without known genetic mutation.

Methods: This IRB-approved single-institution multi-reader study on prospectively acquired FFDM + DBT images included 429 asymptomatic women (39-69y) with an elevated BC risk on their request form. The BCLTR was calculated for each patient using the IBISrisk calculator v8.

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Background: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity).

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Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples.

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Primary tumors with a mixed invasive breast carcinoma of no-special type (IBC-NST) and invasive lobular cancer (ILC) histology are present in approximately five percent of all patients with breast cancer and are understudied at the metastatic level. Here, we characterized the histology of metastases from two patients with primary mixed IBC-NST/ILC from the postmortem tissue donation program UPTIDER (NCT04531696). The 14 and 43 metastatic lesions collected at autopsy had morphological features and E-cadherin staining patterns consistent with pure ILC.

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Article Synopsis
  • Trastuzumab deruxtecan (T-DXd) is now approved for treating HER2-low metastatic breast cancer, but its effectiveness has mostly been studied in clinical trials.
  • The DESTINY-Breast Respond HER2-low Europe study will enroll 1,350 patients across 216 sites in 12 European countries to compare T-DXd with conventional chemotherapy in a real-world setting.
  • This observational study aims to gather data on treatment effectiveness, safety, patient experiences, and overall health, which will help enhance future treatment strategies for patients with advanced breast cancer.
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Article Synopsis
  • * The study aims to implement a new patient-centered care pathway that involves a collaborative team of healthcare professionals to better address the needs of these older patients.
  • * Conducted as a multicentric trial across Europe, the GERONTE study will compare the outcomes of patients receiving this new care approach with those who receive standard oncologic care.
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Introduction: Older patients are often deemed ineligible for clinical research, and many frequently-used endpoints and outcome measures are not as relevant for older patients for younger ones. This systematic review aimed to present an overview of outcomes used in clinical research regarding patients over the age of 65 years with prostate cancer.

Materials And Methods: PubMed and Embase were systematically searched to identify studies on prostate cancer (treatment) in patients aged ≥65 between 2016 and 2023.

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Invasive lobular breast cancer (ILC) differs from invasive breast cancer of no special type in many ways. Evidence on treatment efficacy for ILC is, however, lacking. We studied the degree of documentation and representation of ILC in phase III/IV clinical trials for novel breast cancer treatments.

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