Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors (2023)

  • who: Pauline Rottier and colleagues from the Discovery Institute, United States Kobe University Hospital, Japan have published the research: Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors, in the Journal: (JOURNAL)
  • what: The aim of the study was to assess the prognostic impact of NLR, lymphopenia, PLR and LMR on survival and response rates in women receiving first line CdK4/6i in association with ET for locally advanced or mBC. The aim was to assess the PFS according to pretreatment NLR. Although the results are not significant probably due to the lack of power, the study provided further evidence that lymphopenia is a negative prognostic factor for PFS and OS for patients receiving CdK4/6i. Despite adjustment on confounding factors, the study had some limitations.
  • how: The authors carried out a retrospective single center study at the Comprehensive Cancer Center Francu0327ois Baclesse in Caen France as recommended by REMARK (REporting recommendations for Neutrophil-to-Lymphocyte Ratio NR Not reached PE Pulmonary Embolism PLR Platelet-to-Lymphocyte Ratio TNBC Triple-Negative Breast Cancer VTE Venous ThromboEmbolism. The results are consistent with previous studies.
  • future: The 2 .53 cut-off NLR obtained by ROC curves requires internal and external validation in future studies.

    The authors collected the general characteristics of patients (e_g, age, ECOG-PS, menopausal status), their disease (e_g, TNM staging, hormone_receptor expression and SBR (Scarff Bloom Richardson) grade from the primary tumor site or a current metastatic lesion) and prior therapy (adjuvant treatment, palliative radiotherapy or corticosteroid therapy). On the one hand, neutrophils, B lymphocytes and some CD4+ T_cells may observed in metastatic patients. Increased systemic inflammation markers have been reported in lymphopenic patients, with an inverse increase in the percentage of peripheral neutrophils in response to the expression of pro-inflammatory cytokines such as IL-6 and IL7, CD4+CD8+ double-positive (DP) thymocytes and an agerelated decrease in thymic function or combinatorial T_cell receptor diversity. Cytotoxic CD8+ T_cells are crucial components of tumor-specific cellular adaptive immunity as Thelper (TH) 1, TH17, CD4+ T_cells and Natural Killer cells are in the tumor microenvironment are. A retrospective study of 1,902 patients with eBC showed that a high total and peripheral CD8+ T_cell count was associated with significantly longer breast cancer-specific survival (BCSS). More specifically, in patients with ER-positive tumor, the total number of infiltrating CD8+ T_cells was not significantly associated with patient outcome, whereas peripheral CD8+ count was associated with longer BCSS. Coffelt et_al demonstrated that elevated neutrophil counts induced by BC tumor cells suppressed CD8+ T_cells and promoted metastasis through immunosuppression. The authors did not have complete information on other discriminating factors of immune_response, such as number of B cells, T_cells or CD4/ CD8 ratio, as these are not routinely performed. Indeed, other studies were interested in the NLR prognostic factor, but their population was inhomogeneous as they included patients at the localized and metastatic stage, or metastatic patients only and under cdk4/6 inhibitors but all lines combined without information on previous treatments. @@

  • AE: Adverse events
  • ALC: Absolute lymphocyte count
  • BC: Breast cancer
  • BCSS: Breast cancer-specific survival
  • CR: Complete response
  • CTC: Circulating tumor cells
  • DCR: Disease control rate
  • DFI: Disease-free interval
  • DFS: Disease free survival
  • DP: Double-positive
  • DVT: Deep vein thrombosis
  • EMA: European medicines agency
  • ET: Endocrine therapy
  • FDA: Food and drug administration
  • ILD: Interstitial lung disease
  • LMR: Lymphocyte-tomonocyte ratio
  • NLR: Neutrophil-to-lymphocyte ratio
  • ORR: Objective response rate
  • OS: Overall survival
  • PD: Progressive disease
  • PE: Pulmonary embolism
  • PFS: Progression-free survival
  • PLR: Platelet-to-lymphocyte ratio
  • PR: Partial response
  • ROC: Receiver operating characteristics
  • SD: Stable disease
  • TH: Thelper
  • TILS: Tumor infiltrating lymphocytes
  • TNBC: Triple-negative bc
  • VTE: Venous thromboembolism
  • Receiver operating characteristics: A graphic means for assessing the ability of a screening test to discriminate between healthy and diseased persons; may also be used in other studies, e.g., distinguishing stimuli responses as to a faint stimuli or nonstimuli.
  • prognostic factor: A prediction of the probable outcome of a disease based on a individual`s condition and the usual course of the disease as seen in similar situations.
  • kinase: A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group
  • Adverse events: An adverse event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product
  • Food and drug administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.
  • Breast cancer: Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly-inverted nipple, or a red or scaly patch of skin
  • cyclin: Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle.
  • Endocrine therapy: Estrogen deprivation therapy, also known as endocrine therapy, is a form of hormone therapy that is used in the treatment of breast cancer. Modalities include antiestrogens or estrogen blockers such as selective estrogen receptor modulators like tamoxifen, selective estrogen receptor degraders like fulvestrant, and aromatase inhibitors like anastrozole and ovariectomy
  • Circulating tumor cells: Exfoliate neoplastic cells circulating in the blood and associated with metastasizing tumors.
  • neutrophil: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
  • Complete response: In a clinical research trial, a clinical endpoint generally refers to occurrence of a disease, symptom, sign or laboratory abnormality that constitutes one of the target outcomes of the trial, but may also refer to any such disease or sign that strongly motivates the withdrawal of that individual or entity from the trial, then often termed humane endpoint.
  • Interstitial lung disease: Interstitial lung disease, or diffuse parenchymal lung disease, is a group of lung diseases affecting the interstitium. It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues
  • Progression-free survival: Length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but the disease does not get worse.
  • NLR: NLR may refer to: National Library of Russia, Saint Petersburg National LambdaRail, a high-speed computer network Nazi Lowriders, a white prison and criminal organization New Left Review, a political academic journal Neutrophil to lymphocyte ratio, a marker of subclinical inflammation Newark Light Rail, New Jersey, U.S. Newcastle Light Rail, Newcastle, New South Wales, Australia Nucleotide-binding leucine-rich repeat receptor/NOD-like receptor, a family of intracellular immunoreceptors North London Railway North Little Rock, Arkansas Northampton and Lamport Railway, England Royal Netherlands Aerospace Centre
  • Venous thromboembolism: Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.
  • Progressive disease: Progressive disease or progressive illness is a disease or physical ailment whose course in most cases is the worsening, growth, or spread of the disease. This may happen until death, serious debility, or organ failure occurs
  • Pulmonary embolism: Pulmonary embolism is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream. Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood
  • Disease free survival: Survival rate is a part of survival analysis. It is the percentage of people in a study or treatment group still alive for a given period of time after diagnosis
  • Deep vein thrombosis: The formation or presence of a blood clot (THROMBUS) within a vein.
  • Tumor infiltrating lymphocytes: Tumor-infiltrating lymphocytes are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of u2018tumor-infiltrating immune cellsu2019 which consist of both mononuclear and polymorphonuclear immune cells, in variable proportions

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