Simulated breathing in virtual reality does not affect perceived effort during the physical rehabilitation of people with long COVID.

Objective: To assess the effectiveness of simulated breathing in virtual reality (VR) for manipulating the level of perceived effort of people with long COVID during sessions of physical rehabilitation.

Methods: We conducted a within-participants randomized prospective study during a cycling exercise in immersive VR with three counterbalanced conditions of simulated breathing: slower breathing, neutral breathing, and faster breathing compared to theirs. 37 participants with long COVID and deconditioning were included in the study, 36 of which could finish the experiment.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Circulating tumor cells in breast cancer: clinical validity and utility.

Circulating tumor cells (CTCs) have been extensively studied in breast cancer (BC), with large studies establishing CTCs as a robust prognostic biomarker in early and metastatic breast cancer (MBC). Several phase II and phase III trials have investigated the clinical utility of CTCs in BC. Here, we outline the current landscape for the use of CTCs in the clinic at different stages of BC, focusing first on early BC, then on MBC, with a particular focus on interventional clinical trials based on CTCs.

Plasma ctDNA as a Treatment Response Biomarker in Metastatic Cancers: Evaluation by the RECIST Working Group.

Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease.

Use of Pretreatment Perfusion MRI-based Intratumoral Heterogeneity to Predict Pathologic Response of Triple-Negative Breast Cancer to Neoadjuvant Chemoimmunotherapy.

Background Neoadjuvant chemoimmunotherapy (NACI) has significantly increased the rate of pathologic complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC), although predictors of response to this regimen have not been identified. Purpose To investigate pretreatment perfusion MRI-based radiomics as a predictive marker for pCR in patients with TNBC undergoing NACI. Materials and Methods This prospective study enrolled women with early-stage TNBC who underwent NACI at two different centers from August 2021 to July 2023.

E-Cadherin Mutational Landscape and Outcomes in Breast Invasive Lobular Carcinoma.

Invasive lobular carcinomas (ILC) are characterized by the loss of E-cadherin expression and CDH1 gene inactivation. Diagnostic reproducibility for this tumor type is currently suboptimal and could be improved by a better understanding of its histomolecular and clinical heterogeneity. We have analyzed the relationship between the presence, type, or position of CDH1 mutations, E-cadherin expression, and clinicopathological features (including outcome) in a retrospective series of 251 primary ILC with a long follow-up (median: 9.

Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer.

Background: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody-drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown.

Methods: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC.

Tolerance of Concurrent Adjuvant Radiation Therapy and Pembrolizumab for Triple Negative Breast Cancer: Real Life Experience.

Purpose: The current standard-of-care management of locally advanced triple negative breast cancer (TNBC) is based on neoadjuvant chemo-immunotherapy with pembrolizumab, surgery, radiation therapy (RT), and adjuvant pembrolizumab. However, the safety of combining pembrolizumab with adjuvant breast RT has never been evaluated. This study evaluated the tolerance profile of concurrent pembrolizumab with adjuvant RT in patients with locally advanced TNBC.

Molecular and Clinical Portrait of HER2-low Invasive Lobular Carcinomas.

Invasive lobular carcinomas (ILCs) have a low frequency of ERBB2 amplification, therefore restricting the use of conventional anti-HER2 therapies for this histologic special type. Conversely, ILCs with low HER2 overexpression may represent a broader target for the use of emerging antibody drug conjugate therapies targeting HER2, since these treatments have proven effective in HER2-low breast cancers. Very scarce data about HER2-low ILCs have been so far published, although these tumors could have different prevalence and histomolecular specificities compared with invasive breast carcinoma of no special type (IBC-NST).

Treatment patterns of patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitor-based regimens: a cohort study in the French nationwide healthcare database.

Purpose: To assess real-world treatment patterns in patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) who received cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant at first line.

Methods: Patient characteristics, treatment history, and outcomes data were extracted from the French 'Système National des Données de Santé' (SNDS) database for patients diagnosed with HR+/HER2- mBC between January 2014 and June 2019 and who received combination therapy with a CDK4/6 inhibitor and endocrine therapy. Kaplan-Meier methodology was used to assess time to next treatment (TTNT) and time to treatment discontinuation (TTTD).

AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer.

Background: Window-of-opportunity (WOO) studies provide insights into the clinical activity of new drugs in breast cancer.

Methods: AMEERA-4 (NCT04191382) was a WOO study undertaken to compare the pharmacodynamic effects of amcenestrant, a selective estrogen receptor degrader, with those of letrozole in postmenopausal women with newly diagnosed, operable estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. Women were randomized (1:1:1) to receive amcenestrant 400 mg, amcenestrant 200 mg, or letrozole 2.

Overall Survival With Circulating Tumor Cell Count-Driven Choice of Therapy in Advanced Breast Cancer: A Randomized Trial.

.In patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, the STIC CTC trial established that, for choosing between endocrine therapy (ET) or chemotherapy, the use of circulating tumor cell (CTC) count is noninferior to the investigator's choice in terms of progression-free survival. Here, we report overall survival (OS) results, a secondary end point.

Design of SERENA-6, a phase III switching trial of camizestrant in -mutant breast cancer during first-line treatment.

mutation (m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC.

Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation.

Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis.

Deep learning identifies morphological patterns of homologous recombination deficiency in luminal breast cancers from whole slide images.

Homologous recombination DNA-repair deficiency (HRD) is becoming a well-recognized marker of platinum salt and polyADP-ribose polymerase inhibitor chemotherapies in ovarian and breast cancers. While large-scale screening for HRD using genomic markers is logistically and economically challenging, stained tissue slides are routinely acquired in clinical practice. With the objectives of providing a robust deep-learning method for HRD prediction from tissue slides and identifying related morphological phenotypes, we first show that digital pathology workflows are sensitive to potential biases in the training set, then we propose a method to overcome the influence of these biases, and we develop an interpretation method capable of identifying complex phenotypes.

ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group.

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account.

Clinical Correlations of Programmed Cell Death Ligand 1 Status in Liquid and Standard Biopsies in Breast Cancer.

Background: Data regarding the prognostic value of programmed cell death ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) are lacking. However, CTCs could represent an alternative approach to serial biopsies, allowing real-time monitoring of cancer phenotype.

Methods: We evaluated, in a dedicated prospective clinical trial, the clinicopathological correlations and prognostic value of PD-L1(+)-CTCs in 72 patients with metastatic breast cancer (MBC).

Mutation Detection and Dynamics in Meningeal Carcinomatosis in Breast Cancer.

mutation is frequently encountered in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), especially after aromatase inhibitor (AI) therapy, as a mechanism of resistance to endocrine therapy. Circulating tumor DNA-based detection of mutation in plasma has been demonstrated as a prognostic and predictive factor for poor outcomes in subsequent AI therapy. In this case report, for the first time, we describe the detection of mutation (p.

ShallowHRD: detection of homologous recombination deficiency from shallow whole genome sequencing.

Summary: We introduce shallowHRD, a software tool to evaluate tumor homologous recombination deficiency (HRD) based on whole genome sequencing (WGS) at low coverage (shallow WGS or sWGS; ∼1X coverage). The tool, based on mining copy number alterations profile, implements a fast and straightforward procedure that shows 87.5% sensitivity and 90.