Publications by authors named "Severine Guiu"

Background: The cutoff of <1% positive cells to define estrogen receptor (ER) negativity by immunohistochemistry (IHC) in breast cancer (BC) is debated. We explored the tumor immune microenvironment and gene-expression profile of patients with early-stage HER2-negative ER-low (ER 1%-9%) BC, comparing them to ER-negative (ER <1%) and ER-intermediate (ER 10%-50%) tumors.

Methods: Among 921 patients with early-stage I-III, ER ≤50%, HER2-negative BCs, tumors were classified as ER-negative (n = 712), ER-low (n = 128), or ER-intermediate (n = 81).

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Background & Aims: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are the cornerstone of systemic therapy for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer. In the various therapeutic studies with CDK4/6 inhibitors, elevations in liver tests were more frequent than in the control groups. The mechanism of CDK4/6 inhibitor-induced liver toxicity is not well understood; moreover, natural history and appropriate management are poorly described.

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Importance: Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC).

Objective: To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan.

Design, Setting, And Participants: This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022.

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Article Synopsis
  • Triple-negative breast cancer (TNBC) has a poor prognosis, and cathepsin D (cath-D) is a key target for antibody therapies to enhance natural killer (NK) cell activity against tumors.
  • This study explored the effectiveness of engineered anti-cath-D antibodies in triggering NK cell-mediated attacks (ADCC) and their potential in combination therapies for TNBC.
  • Results showed that the Fc-engineered antibodies activated NK cells and promoted ADCC against TNBC cells, suggesting their promise as a treatment strategy when used alongside other therapies.
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Background: For several years, the AXL tyrosine kinase receptor, a member of the Tyro3-Axl-Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL CTCs) could be clinically relevant.

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Background And Purpose: Triple-negative breast cancer (TNBC) has poorer outcomes than other breast cancers (BC), including HER2 BC. Cathepsin D (CathD) is a poor prognosis marker overproduced by BC cells, hypersecreted in the tumour microenvironment with tumour-promoting activity. Here, we characterized the immunomodulatory activity of the anti-CathD antibody F1 and its improved Fab-aglycosylated version (F1M1) in immunocompetent mouse models of TNBC (C57BL/6 mice harbouring E0771 cell grafts) and HER2-amplified BC (BALB/c mice harbouring TUBO cell grafts).

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Importance: In ERBB2 (formerly HER2)-positive metastatic breast cancer (MBC), combining trastuzumab and pertuzumab with taxane-based chemotherapy is the first line of standard care. Given that trastuzumab plus pertuzumab was proven effective in ERBB2-positive MBC, even without chemotherapy, whether the optimal first-line strategy could be trastuzumab plus pertuzumab alone instead of with chemotherapy is unresolved.

Objective: To assess overall survival (OS) at 2 years and progression-free survival (PFS) for patients randomly assigned to receive first-line pertuzumab plus trastuzumab alone or with chemotherapy followed by trastuzumab and emtansine at progression; PFS of second-line trastuzumab and emtansine treatment following trastuzumab plus pertuzumab; and OS and PFS in the ERBB2-enriched and ERBB2-nonenriched subtypes.

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Everolimus is the first oral targeted therapy widely used in advanced HR+/HER2- breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period.

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Background: T cell immunoreceptor with Ig and ITIM domains (TIGIT) interacts with poliovirus receptor (PVR) to contribute to cancer immune escape. Recently, TIGIT and PVR have been identified as promising immunotherapy targets. Their gene expression is upregulated in many solid tumors, but their protein expression level is not well documented, particularly in triple negative breast cancer (TNBC), the breast cancer subtype that most benefit from immunotherapy.

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Importance: Evidence suggests that patients with human epidermal growth factor receptor 2-positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting.

Objective: To evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC.

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Introduction: Several studies have shown that emotional competence (EC) impacts cancer adjustment via anxiety and depression symptoms. The objective was to test this model for the quality of life (QoL) of partners: first, the direct effect of partners' EC on their QoL, anxiety and depression symptoms after cancer diagnosis (T1), after chemotherapy (T2) and after radiotherapy (T3); Second, the indirect effects of partners' EC at T1 on their QoL at T2 and T3 through anxiety and depression symptoms.

Methods: 192 partners of women with breast cancer completed a questionnaire at T1, T2 and T3 to assess their EC (PEC), anxiety and depression symptoms (HADS) and QoL (Partner-YW-BCI).

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Article Synopsis
  • Triple-negative breast cancer (TNBC) is a highly aggressive cancer type that currently lacks specific targeted treatments, and a protein called SPARC may play a significant role in its progression.
  • In a study of 148 non-metastatic TNBC patients, it was found that high SPARC expression in cancer-associated fibroblasts (CAFs) is linked to poorer recurrence-free survival, making it an important independent prognostic factor.
  • The research also indicates that targeting SPARC in CAFs could offer a potential new therapeutic strategy for patients with TNBC, especially those showing SPARC expression.
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Background: Acceptability and tolerance of chemotherapy on patients treated for breast cancer remain challenging. Complementary approaches such as hypnosis may have a favorable impact both at the time of announcing and during chemotherapy, due to the notorious anxiety, distress, and self-perceived dysfunction. The objective of the study was that the patients complied with at least four self-hypnosis sessions out of the six cycles of chemotherapy.

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Background: Taxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies.

Methods: We analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3-24 months after previous (neo)adjuvant taxanes treatment.

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Article Synopsis
  • Palbociclib is considered suitable for therapeutic drug monitoring due to its narrow therapeutic range and high incidence of serious side effects like neutropenia.
  • A clinical trial involving 58 patients showed a correlation between palbociclib plasma levels and the occurrence of high-grade neutropenia, especially in those with lower neutrophil counts at treatment start.
  • Drug interactions significantly impacted palbociclib plasma levels, with certain co-treatments increasing or decreasing concentrations, but these interactions did not significantly affect the rates of high-grade neutropenia.
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A 48-year-old woman was referred for a bone scan as an assessment of bone metastasis from breast cancer. Surprisingly, two hot spots of lung uptake were present in the left lung without any abnormality on CT slices. No history of pulmonary disease was observed.

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Background: The impact of the histological lobular subtype on overall survival (OS) in metastatic breast cancer (MBC) is still under debate, with very few data available.

Patients And Methods: Using the French national multicentre Epidemiological Strategy and Medico Economics [ESME]) data platform, the primary objective was to compare the OS of patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) MBC, with adjustment on the main prognostic factors using two approaches: multivariable analysis and matching with a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1) and describe patients and tumour characteristics.

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Background: Breast cancer (BC) in young women merits a specific approach given the associated fertility, genetic and psychosocial issues. metastatic breast cancer (MBC) in young women is an even more serious condition, with limited data available.

Methods: We evaluated management of women aged ⩽40 years with MBC in a real-life national multicentre cohort of 22,463 patients treated between 2008 and 2016 (NCT0327531).

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Objective: Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women (≤45 years) with breast cancer (YWBC) on their specific quality of life (i.e.

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Article Synopsis
  • HER2-low breast cancer, particularly within the triple-negative breast cancer (TNBC) subtype, shows limited existing data with a study examining HER2 expression and its impact on patient prognosis.
  • Out of 296 TNBC samples assessed, the majority were classified as HER2 0, with only a small percentage being HER2 1+ or 2+, and differences in tumor characteristics were observed between these groups.
  • A follow-up of nearly 10 years indicated that patients with HER2 2+ tumors had significantly worse relapse-free survival compared to those with HER2 0/1+ tumors, although overall survival did not show a major distinction between these groups.
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Purpose: Pharmacist consultation is unfrequently performed in oncology clinical trials that include patients who often have many co-treatments increasing the risk of drug-drug interactions (DDI). The aim of this study was to determine whether best possible medication history (BPMH) by hospital pharmacist at inclusion and therapeutic drug monitoring could be used for DDI risk evaluation and for current oral targeted therapy management.

Methods: A prospective clinical trial (ALCINA 2, NCT04025541) was carried out in metastatic breast cancer cohort treated by palbociclib to conduct pharmacokinetics-toxicity correlation study.

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Background: Changes in calcium metabolism and calcium urinary excretion during chemotherapy have not been thoroughly assessed in patients with early breast cancer (EBC), a population who frequently present vitamin D insufficiency. As hypercalciuria is a classical contra-indication to vitamin D (VD) supplementation, this study evaluated changes in VD and calcium metabolism parameters in patients with EBC undergoing adjuvant chemotherapy (CT).

Methods: In patients with EBC who received six cycles of adjuvant CT, VD and calcium parameters were monitored at inclusion, and then every 3 weeks, at each CT cycle initiation.

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Alternative therapeutic strategies based on tumor-specific molecular targets are urgently needed for triple-negative breast cancer (TNBC). The protease cathepsin D (cath-D) is a marker of poor prognosis in TNBC and a tumor-specific extracellular target for antibody-based therapy. The identification of cath-D substrates is crucial for the mechanistic understanding of its role in the TNBC microenvironment and future therapeutic developments.

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The prognostic impact of the different tumor-infiltrating lymphocyte (TIL) subpopulations in solid cancers is still debated. Here, we investigated the clinicopathological correlates and prognostic impact of TILs, particularly of γδ T cells, in 162 patients with triple-negative breast cancer (TNBC). A high γδ T cell density (>6.

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Background: Inflammatory blood markers, such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been reported as putative prognostic factors for survival and predictive factors for pathological complete response and toxicity in cancers, however with conflicting results.

Methods: We retrospectively analyzed data of 280 patients with early breast cancer receiving neo-adjuvant chemotherapy between 2005 and 2013 in our center. Neutrophil count, lymphocyte count and platelet count before treatment were collected as well as data on pathological complete response, toxicity, recurrence and survival.

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