A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial.

BACKGROUND: Oral anticancer therapies such as protein kinase inhibitors (PKIs) are increasingly prescribed in cancer care. We aimed to evaluate the impact of a pharmacist-led interprofessional medication adherence program (IMAP) on patient implementation (dosing history), persistence (time until premature cessation of the treatment) and adherence to 27 PKIs prescribed for various solid cancers, as well as the impact on patients' beliefs about medicines (BAM) and quality of life (QoL). METHODS: Patients (n = 118) were randomized 1:1 into two arms. In the intervention arm, pharmacists supported patient adherence through monthly electronic and motivational feedback, including educational, behavioral and affective components, for 12 months. The control arm received standard care plus EM without intervention. All PKIs were delivered in electronic monitors (EMs). Medication implementation and adherence were compared between groups using generalized estimating equation models, in which relevant covariables were included; persistence was compared with Kaplan‒Meier curves. Information on all treatment interruptions was compiled for the analysis. Questionnaires to evaluate BAM and QoL were completed among patients who refused and those who accepted to participate at inclusion, 6 and 12 months post-inclusion or at study exit. RESULTS: Day-by-day PKI implementation was consistently higher and statistically significant in the intervention arm (n = 58) than in the control arm (n = 60), with 98.1% and 95.0% (Δ3.1%, 95% confidence interval (CI) of the difference 2.5%; 3.7%) implementation at 6 months, respectively. The probabilities of persistence and adherence were not different between groups, and no difference was found between groups for BAM and QoL scores. No difference in BAM or QoL was found among patients who refused versus those who participated. The intervention benefited mostly men (at 6 months, Δ4.7%, 95% CI 3.4%; 6.0%), those younger than 60 years (Δ4.0%, 95% CI 3.1%; 4.9%), those who had initiated PKI more than 60 days ago before inclusion (Δ4.5%, 95% CI 3.6%; 5.4%), patients without metastasis (Δ4.5%, 95% CI 3.4%; 5.7%), those who were diagnosed with metastasis more than 2 years ago (Δ5.3%, 95% CI 4.3%; 6.4%) and those who had never used any adherence tool before inclusion (Δ3.8%, 95% CI 3.1%; 4.5%). CONCLUSIONS: The IMAP, led by pharmacists in the context of an interprofessional collaborative practice, supported adherence, specifically implementation, to PKIs among patients with solid cancers. To manage adverse drug events, PKI transient interruptions are often mandated as part of a strategy for treatment and adherence optimization according to guidelines. Implementation of longer-term medication adherence interventions in the daily clinic may contribute to the improvement of progression-free survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484064.

[Male breast cancer: a lesser-known battle]. / Cancer du sein chez l'homme : un combat méconnu.

Breast cancer in men is a rare and understudied disease. Until recently, prospective studies and clinical trials on breast cancer treatments often excluded men. Treatment recommendations were generally extrapolated from the results of clinical trials that included only women. Significant efforts have been made to better understand the biological characteristics, the most effective treatments, and the outcomes of breast cancer in men, as well as to identify clinically relevant differences of this disease. This article reviews the current data on the epidemiology, pathological and clinical characteristics, as well as the treatment of breast cancer in men.

Le cancer du sein chez l'homme est une maladie rare et peu étudiée. Jusqu'à récemment, les études prospectives et les essais cliniques sur les traitements du cancer du sein excluaient souvent les hommes. Les recommandations de traitement étaient généralement extrapolées à partir des résultats d'essais cliniques incluant uniquement des femmes. Des efforts significatifs ont été déployés pour mieux comprendre les caractéristiques biologiques, les traitements les plus efficaces et les résultats du cancer du sein chez les hommes, ainsi que pour identifier les différences cliniquement pertinentes de cette maladie. Cet article passe en revue les données actuelles sur l'épidémiologie, les caractéristiques pathologiques et cliniques, ainsi que le traitement du cancer du sein chez l'homme.

Neo-adjuvant therapies for ER positive/HER2 negative breast cancers: from chemotherapy to hormonal therapy, CDK inhibitors, and beyond.

INTRODUCTION: Chemotherapy has been traditionally used as neo-adjuvant therapy in breast cancer for down-staging of locally advanced disease in all sub-types. In the adjuvant setting, genomic assays have shown that a significant proportion of ER positive/HER2 negative patients do not derive benefit from the addition of chemotherapy to adjuvant endocrine therapy. An interest in hormonal treatments as neo-adjuvant therapies in ER positive/HER2 negative cancers has been borne by their documented success in the adjuvant setting. Moreover, cytotoxic chemotherapy is less effective in ER positive/HER2 negative disease compared with other breast cancer subtypes in obtaining pathologic complete responses. AREAS COVERED: Neo-adjuvant therapies for ER positive/HER2 negative breast cancers and associated biomarkers are reviewed, using a Medline survey. A focus of discussion is the prediction of patients that are unlikely to derive extra benefit from chemotherapy and have the highest probabilities of benefiting from hormonal and other targeted therapies. EXPERT OPINION: Predictive biomarkers of response to neo-adjuvant chemotherapy and hormonal therapies are instrumental for selecting ER positive/HER2 negative breast cancer patients for each treatment. Chemotherapy remains the standard of care for many of those patients requiring neo-adjuvant treatment, but other neo-adjuvant therapies are increasingly used.

[Oncology: what's new in 2023]. / Oncologie: ce qui a changé en 2023.

The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.

Le domaine de l'oncologie poursuit son évolution remarquable au fil des années, avec des avancées prometteuses ouvrant la voie à des traitements novateurs et individualisés. L'élaboration de nouvelles molécules, l'identification de nouvelles cibles thérapeutiques et la recherche de nouvelles séquences ou combinaisons de traitements promettent de révolutionner la prise en charge du cancer et de contribuer à améliorer les taux de survie, la qualité de vie des patients et à ouvrir de nouvelles perspectives dans la recherche en oncologie. Dans cet article, les nouveautés parues en 2023 sont passées en revue.

Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies.

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1ß, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.

Homologous Recombination Defects and Mutations in DNA Damage Response (DDR) Genes Besides BRCA1 and BRCA2 as Breast Cancer Biomarkers for PARP Inhibitors and Other DDR Targeting Therapies.

Homologous recombination repair (HRR) is the cellular mechanism for error-free repair of double strand DNA (dsDNA) breaks. Cancer cells with mutations in both alleles of genes encoding for proteins involved in HRR, such as BRCA1 and BRCA2, have defects in the repair process. As a result, these cells repair dsDNA breaks with alternative mechanisms, such as non-homologous end joining. In breast cancers with germline mutations in BRCA1 and BRCA2 genes, HRR defects result in sensitivity to PARP inhibitors, drugs that interfere with the function of PARP enzyme and promote trapping of the enzyme on DNA and stalling of the process of repairing single strand breaks. HRR defects also lead to sensitivity to DNA damaging chemotherapy due to the inability of cells to repair chemotherapy induced DNA lesions. Besides germline mutations in BRCA1 and BRCA2, somatic mutations in these genes or germline and somatic mutations or other genetic and epigenetic alterations of other genes involved in homologous recombination (HR) may produce HRR defects leading to sensitivity to PARP inhibitors. However, studies are less conclusive, a fact that may relate to the common lack of bi-allelic loss of function in these cases, as opposed to cancers with germline BRCA1 or BRCA2 defects that usually acquire bi-allelic loss of function. In addition, there is heterogeneity between the different HRR genes and the severity of the resulting HRR defects, as measured by HR defect assays. This review article examines the landscape of HRR gene mutations in breast cancer and the possible therapeutic implications of HRR defects other than germline BRCA1 and BRCA2 mutations for targeted therapies. Identification of a wider range of breast cancers with HRR defects may expand the subset of patients that derive benefit from PARP inhibitors and other DDR-targeting drugs in the clinic.

Adherence to the CDK 4/6 Inhibitor Palbociclib and Omission of Dose Management Supported by Pharmacometric Modelling as Part of the OpTAT Study.

The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Δ1.95%, 95% CI 1.1−2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1−5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7−4.8%) and patients >65 (Δ2.3%, 95% CI 0.8−3.6%). Simulations showed that 25% of patients had neutropenia grade ≥3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity.

[Oncology: what's new in 2022]. / Oncologie : ce qui a changé en 2022.

The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers. Here we present the major advances in solid tumors.

L'année écoulée a apporté son lot d'innovations en oncologie médicale, ouvrant de nouvelles options prometteuses pour bon nombre de tumeurs solides, qu'elles soient localisées ou métastatiques. L'immunothérapie, véritable fer de lance des thérapies émergentes dans les maladies métastatiques, voit son usage s'étendre à des modalités adjuvantes et néoadjuvantes, notamment dans les cancers du côlon et du poumon. 2022 donne également la part belle aux thérapies ciblées mais aussi aux conjuguées anticorps-médicaments qui apportent de nouveaux standards tant pour les cancers du sein que du poumon. Nous vous présentons ici les avancées majeures concernant les tumeurs solides.

Population Pharmacokinetics of Palbociclib and Its Correlation with Clinical Efficacy and Safety in Patients with Advanced Breast Cancer.

Neutropenia is the most frequent dose-limiting toxicity reported in patients with metastatic breast cancer receiving palbociclib. The objective of this study was to investigate the pharmacokinetic-pharmacodynamic (PK/PD) relationships for toxicity (i.e., absolute neutrophil count, ANC) and efficacy (i.e., progression-free survival, PFS). A semi-mechanistic PK/PD model was used to predict neutrophils' time course using a population approach (NONMEM). Influence of demographic and clinical characteristics was evaluated. Cox proportional hazards models were developed to evaluate the influence of palbociclib PK on PFS. A two-compartment model with first-order absorption and a lag time adequately described the 255 palbociclib concentrations provided by 44 patients. The effect of the co-administration of proton-pump inhibitors in fasting conditions increased palbociclib clearance by 56%. None of the tested covariates affected the PD parameters. Model-based simulations confirmed the concentration-dependent and non-cumulative properties of palbociclib-induced neutropenia, reversible after treatment withdrawal. The ANC nadir occurred approximately at day 24 of each cycle. Cox analyses revealed a trend for better PFS with increasing palbociclib exposure in older patients. By characterizing palbociclib-induced neutropenia, this model offers support to clinicians to rationally optimize treatment management through patient-individualized strategies.

Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.

Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-ß-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option.

[Adverse effects of new breast cancer therapies : when to react ?] / Effets indésirables des nouvelles thérapies du cancer du sein : quand faut-il réagir ?

In last years, the therapeutic arsenal against breast cancer increased considerably with the arrival of signaling pathway inhibitors, immunotherapy, PARP inhibitors, tyrosine kinase inhibitors and antibody-drug conjugates. Consequently, the range of potential adverse events has also widened and differs from the usual chemotherapies and endocrine therapies. Depending on the administered therapy, the same symptoms can be harmless and treated symptomatically or the warning sign of a potential serious complication requiring a rapid action. We therefore discuss in this article the therapeutic role and some typical adverse events of these new therapies.

Ces dernières années, l'arsenal thérapeutique contre le cancer du sein s'est passablement enrichi avec les inhibiteurs des voies de signalisation, l'immunothérapie, les inhibiteurs de PARP (polyADP-ribose polymérase), les inhibiteurs de tyrosine kinase et les chimiothérapies immunoconjuguées. De ce fait, la gamme d'effets indésirables potentiels s'est également élargie et diffère des habituelles chimiothérapies et hormonothérapies. En fonction de la substance administrée, les mêmes symptômes peuvent être anodins et traités symptomatiquement, ou alors être le signe d'alerte d'une potentielle complication sévère et nécessiter une réaction rapide. Nous discutons dans cet article du rôle thérapeutique et des quelques effets indésirables typiques de ces nouvelles thérapies.

Neurotrophic receptor tyrosine kinase family members in secretory and non-secretory breast carcinomas.

BACKGROUND: Breast cancer is the most common female cancer and a major cause of morbidity and mortality. Progress in breast cancer therapeutics has been attained with the introduction of targeted therapies for specific sub-sets. However, other subsets lack targeted interventions and thus there is persisting need for identification and characterization of molecular targets in order to advance breast cancer therapeutics. AIM: To analyze the role of lesions in neurotrophic receptor tyrosine kinase (NTRK) genes in breast cancers. METHODS: Analysis of publicly available genomic breast cancer datasets was performed for identification and characterization of cases with fusions and other molecular abnormalities involving NTRK1, NTRK2 and NTRK3 genes. RESULTS: NTRK fusions are present in a small number of breast cancers at the extensive GENIE project data set which contains more than 10000 breast cancers. These cases are not identified as secretory in the database, suggesting that the histologic characterization is not always evident. In the breast cancer The Cancer Genome Atlas (TCGA) cohort the more common molecular lesion in NTRK genes is amplification of NTRK1 observed in 7.9% of breast cancers. CONCLUSION: Neurotrophin receptors molecular lesions other than fusions are observed more often than fusions. However, currently available NTRK inhibitors are effective mainly for fusion lesions. Amplifications of NTRK1, being more frequent in breast cancers, could be a viable therapeutic target if inhibitors efficacious for them become available.

[2021 Oncology update]. / Oncologie.

Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.

En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.

Optimizing Oral Targeted Anticancer Therapies Study for Patients With Solid Cancer: Protocol for a Randomized Controlled Medication Adherence Program Along With Systematic Collection and Modeling of Pharmacokinetic and Pharmacodynamic Data.

BACKGROUND: The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. OBJECTIVE: The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. METHODS: The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. RESULTS: The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. CONCLUSIONS: The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients' needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30090.

[Breast cancer during pregnancy]. / Cancer du sein chez la femme en.

The management of patients with breast cancer during their pregnancy is challenging. A good coordination is required between the oncology and obstetrics teams in order to ensure appropriate care, while providing a reassuring environment during this stressful period. Most often, the pregnancy can continue without delaying the initiation of oncological treatments, offering a prognosis similar to non-pregnant women. Surgery and chemotherapy can be done during pregnancy, unlike endocrine therapy, radiotherapy and antibody treatments which can only be given postpartum. While some imaging techniques are compatible, others require special measures or are contraindicated. We discuss these points in the context of a clinical situation.

La prise en charge des patientes présentant un cancer du sein durant leur grossesse est un challenge. Elle exige une bonne coordination entre les équipes oncologique et obstétricale afin d'assurer des soins appropriés tout en offrant un cadre rassurant en cette période de grand stress. Le plus souvent, la grossesse peut être poursuivie sans retarder l'initiation des traitements oncologiques, avec un pronostic similaire aux femmes non enceintes. La chirurgie et la chimiothérapie peuvent être entreprises en cours de grossesse, contrairement à l'hormonothérapie, la radiothérapie et les traitements par anticorps qui ne peuvent être administrés qu'en post-partum. Si certaines techniques d'imagerie sont compatibles, d'autres requièrent des mesures particulières ou sont contre-indiquées. Nous discutons de ces points dans le cadre d'une situation clinique.

Intraductal xenografts show lobular carcinoma cells rely on their own extracellular matrix and LOXL1.

Invasive lobular carcinoma (ILC) is the most frequent special histological subtype of breast cancer, typically characterized by loss of E-cadherin. It has clinical features distinct from other estrogen receptor-positive (ER+ ) breast cancers but the molecular mechanisms underlying its characteristic biology are poorly understood because we lack experimental models to study them. Here, we recapitulate the human disease, including its metastatic pattern, by grafting ILC-derived breast cancer cell lines, SUM-44 PE and MDA-MB-134-VI cells, into the mouse milk ducts. Using patient-derived intraductal xenografts from lobular and non-lobular ER+ HER2- tumors to compare global gene expression, we identify extracellular matrix modulation as a lobular carcinoma cell-intrinsic trait. Analysis of TCGA patient datasets shows matrisome signature is enriched in lobular carcinomas with overexpression of elastin, collagens, and the collagen modifying enzyme LOXL1. Treatment with the pan LOX inhibitor BAPN and silencing of LOXL1 expression decrease tumor growth, invasion, and metastasis by disrupting ECM structure resulting in decreased ER signaling. We conclude that LOXL1 inhibition is a promising therapeutic strategy for ILC.

Chemotherapy and targeted treatments of breast sarcoma by histologic subtype.

Introduction: Breast sarcomas (BS) are uncommon and often present both diagnostic and therapeutic challenges. Historically, radical surgery has been the mainstay of treatment for localized breast sarcomas. On the other hand, in advanced disease, since they are a heterogeneous group of neoplasms consisting of several different subtypes including angiosarcoma, phyllodes tumor, and pleomorphic undifferentiated sarcoma, there is a lack of proven specific therapy. As a result, their treatment is based on the soft tissue sarcoma (STS) paradigm, whereas histotype-tailored approaches apply to specific subtypes like dermatofibrosarcoma protuberans. To date, advanced stages constitute an incurable form of disease and chemotherapy remains the cornerstone of treatment with the aim of palliation of symptoms and increase in survival.Areas covered: In this manuscript, we review the clinicopathologic characteristics of the most common subtypes of BS, as well as the current treatment landscape of BS, with a particular focus on opportunities and challenges provided by new targeted molecules and immunotherapy.Expert opinion: The treatment approach of advanced BS is based on the pathologic subtype. A true breakthrough has still to be obtained, as the development of new agents in BS suffers from the same weaknesses as in other STS.

[2020 oncology update]. / Oncologie.

The COVID-19 pandemic that has swept around the world in early 2020 has changed our daily practice and habits. Fortunately, however, 2020 also brings its share of new approaches and therapeutic combinations as well as new therapies. These advances are improving the outcomes and quality of life of our patients across the spectrum of oncological diseases. This article summarises the latest oncological advances and novelties for 2020 in the following tumor entities : lung, breast, digestive, gynecological, urological and ENT.

La pandémie de Covid-19 survenue début 2020 dans le monde entier aura bouleversé notre pratique quotidienne et nos habitudes. Heureusement, sur le plan thérapeutique, l'année 2020 apporte également son lot de nouvelles approches et combinaisons thérapeutiques ainsi que l'introduction de nouvelles molécules, permettant d'améliorer le pronostic vital et la qualité de vie de nos patients, dans de nombreux domaines. Cet article résume les dernières avancées et nouveautés oncologiques de l'année 2020 dans les domaines suivants : poumon, sein, sphère digestive, gynécologique, urologique et ORL.

The Future of ER+/HER2- Metastatic Breast Cancer Therapy: Beyond PI3K Inhibitors.

Most breast cancers express the estrogen receptor (ER) receptor and are negative for the human epidermal growth factor receptor 2 (HER2) receptor. ER+/HER2- cancers are treated with hormone-based therapies in the adjuvant setting and derive significant survival benefit from these therapies in the metastatic setting. However, hormone resistance develops in most metastatic patients. An increased understanding of the biology of ER+/HER2- breast cancers has led to the development of new therapies for this disease including CDK4/6 inhibitors and PI3K inhibitors. Several other neoplastic processes are targeted by novel drugs in clinical development, addressing cancer vulnerabilities. These include newer ways to block the ER and targeting the HER2 receptors in ER+/HER2- cancers expressing HER2 in low levels not qualifying for clinical positivity. In addition, promising therapeutic options include targeting other surface receptors or their downstream pathways, as well as targeting the apoptotic machinery and boosting the immune response which is initially insufficient in these cancers. A selection of new drugs in advanced development for ER+/HER2- breast cancer will be discussed in this review.

Oncology during the COVID-19 pandemic: challenges, dilemmas and the psychosocial impact on cancer patients.

COVID-19 has caused unprecedented societal turmoil, triggering a rapid, still ongoing, transformation of healthcare provision on a global level. In this new landscape, it is highly important to acknowledge the challenges this pandemic poses on the care of the particularly vulnerable cancer patients and the subsequent psychosocial impact on them. We have outlined our clinical experience in managing patients with gastrointestinal, hematological, gynaecological, dermatological, neurological, thyroid, lung and paediatric cancers in the COVID-19 era and have reviewed the emerging literature around barriers to care of oncology patients and how this crisis affects them. Moreover, evolving treatment strategies and novel ways of addressing the needs of oncology patients in the new context of the pandemic are discussed.