0000000000084125
AUTHOR
Isabelle Desmoulins
Population Pharmacokinetics of Palbociclib in aReal-World Situation
Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrat…
Fertility concerns among young breast cancer survivors in Côte d’Or
Introduction Les effets secondaires des traitements utilises dans la prise en charge du cancer du sein (CS) sur la fonction ovarienne et la fertilite ont largement ete documentes. Cependant, les donnees populationnelles sur les difficultes liees a la fertilite des survivantes jeunes apres un CS sont rares et peu d’etudes ont ete realisees sur cette thematique en France. Cette etude visait a decrire les conditions de vie a long terme, en termes de fertilite, des survivantes jeunes apres un CS en Cote d’Or. Methodes Les femmes âgees de 45 ans et moins au diagnostic d’un CS non metastatique entre 2006 et 2015, ont ete selectionnees a partir du Registre des CS et autres cancers gynecologiques d…
Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients
Palbociclib is an oral CDK4/6 inhibitor indicated in HR+/HER2- advanced or metastatic breast cancer in combination with hormonotherapy. Its main toxicity is neutropenia. The aim of our study was to describe the kinetics of circulating neutrophils from real-life palbociclib-treated patients. A population pharmacokinetic (popPK) model was first constructed to describe palbociclib pharmacokinetic (PK). Individual PK parameters obtained were then used in the pharmacokinetic/pharmacodynamic (PK/PD) model to depict the relation between palbociclib concentrations and absolute neutrophil counts (ANC). The models were built with a population of 143 patients. Palbociclib samples were routinely collec…
Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.
Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analy…
Prognostic Factors of Survival among Women with Metastatic Breast Cancer and Impact of Primary or Secondary Nature of Disease on Survival: A French Population-Based Study.
We aim to determine whether differences in survival exist between two populations of women with metastatic breast cancer (MBC) and to identify prognostic factors of survival after metastasis diagnosis. Data on women with MBC diagnosed between 2000 and 2011 were provided by the Cote d'Or Breast cancer registry. Survival rates and median overall survival (OS) after metastasis diagnosis were determined using the Kaplan–Meier method and prognostic factors were determined in a Cox proportional hazard model. Overall, 282 women with primary MBC and 340 with secondary MBC were included. A 2-year survival rate was significantly better in women with primary MBC (50.8% [95% CI: 47.8–53.8%] versus 44.5…
La réponse immunitaire anti-tumorale dans le cancer du sein : état des lieux et perspectives thérapeutiques
The role of the immune response in breast cancer is now well recognized and increasingly taken in account. The goal of this article is, in the first part, to underline its prognostic impact and to precise the immunosurvelliance, immunoselection and the immunosubversion concepts involved in the control and evasion of breast carcinoma. In the second part, therapeutic strategies for the restauration of anti-tumor immunity are developed. Vaccination strategies and checkpoints inhibitors blockade strategies are discussed as well as the immunogenic death linked to the conventional treatments of breast cancer.
Stratégies en cas de positivité du ganglion sentinelle dans les cancers du sein
Resume Les strategies de prise en charge en cas de ganglion(s) sentinelle(s) micro ou macrometastatique(s) dans les cancers du sein ont ete profondement modifiees depuis une dizaine d’annees et la publication de cinq essais randomises : ACOSOG Z0011, IBCSG 23-01, et AATRM comparant curage axillaire versus abstention ; et AMAROS et OTOASOR comparant curage axillaire versus radiotherapie axillaire. Malgre les limites methodologiques de certains de ces essais, notamment de l’ACOSOG Z0011, les recommandations internationales (ASCO, NCCN) et le consensus d’experts de St Gallen ne preconisent pas la realisation d’un curage axillaire complementaire en cas d’envahissement macro ou micrometastatique…
Stage IV breast cancer: a population-based study about prognostic factors according to HER2 and HR status
International audience; We aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte-d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in patients with HER2-positive tumours who did not …
Breast cancer subtype of French women is not influenced by socioeconomic status: A population-based-study
Context The molecular subtype of breast tumours plays a major role in cancer prognosis and treatment options. Triple negative tumours (TN) carry the worst prognosis and affects most frequently women of low socioeconomic status (SES). Studies have shown that non-biologic factors, such as the socioeconomic status could have an influence on tumour biology. To this date no study has been done investigating this association in French women. The objective is to study the association between the SES and the molecular tumour subtype of breast cancer patients in the French county of Cote d’Or. This study benefits from the population data from the Cote d’Or breast cancer registry known for its strict…
Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort
Summary Purpose In the ACOSOG Z0011 trial, patients with primary breast cancer and 1–2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The ai…
Seroprevalence of SARs-CoV-2 among the staff and patients of a French cancer centre after first lockdown: the canSEROcov study
Abstract Background In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection. Methods After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to unde…
Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.
Abstract Purpose: To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC). Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its chan…
Tumeurs localisées du sein triple négatives en 2016 : définitions et prise en charge
Triple-negative breast cancer (TN), as defined by the triple negativity in immunohistochemistry: the absence of estrogen receptor, progesterone receptor and the absence of overexpression or amplification of HER2, corresponds to 15 % of invasive breast cancers. This is a very heterogeneous group of tumors both at the genomic and transcriptomic level and at morphological, clinical and prognostic level. Although there are some good prognosis forms, the majority of TN tumors is characterized by a poor prognosis with a greater frequency of visceral metastases and a maximum risk of relapse in the first two years after diagnosis. Systemic adjuvant treatment with chemotherapy is almost always indic…
G-CSF dosing schedule to prevent eribulin-induced neutropenia: Can modelling and simulation help?
e20673 Background: Eribulin is a microtubule inhibitor indicated for the treatment of patients with metastatic breast cancer and should be administered on day 1 and 8 of each 21-day cycle. Neutrope...