Frédérique Penault-Llorca

• Research Director at Centre Jean Perrin

Proteins normally localized in the intracellular compartments of healthy cells, have been observed at the surface of cancer cells, despite not having transmembrane domain or secretion signals. The unexpected localization of these externalized proteins is likely to reflect currently unknown functions. Their presence on the cell surface presents a un...

Background/aim: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype, posing numerous challenges in clinical decision-making. Biomarkers are essential to personalize management of TNBC patients. While tumor infiltrating lymphocytes (TILs) are validated prognostic biomarkers, the requirement for tumor biopsy limits t...

Context.—: Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment of metastatic breast cancer with low level of human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis of HER2-low status defined by immunohistochemistry IHC 1+...

Background The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus. Methods During the 14th Breast‐Gynecological and Imm...

Background Longer times between diagnosis and treatments of cancer patients have been estimated as effects of the COVID-19 pandemic. However, relatively few studies attempted to estimate actual delay to treatment at the patient level. Objective To assess changes in delays to first treatment and surgery among newly diagnosed patients with localized...

Background Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). Methods 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were ran...

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast...

Background: DESTINY-Breast04 (DB-04) showed that trastuzumab deruxtecan improves survival vs chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry [IHC] 1+ or IHC 2+ with in situ hybridization negative) metastatic breast cancer (BC). The VENTANA 4B5(CDx) IHC assay, now approved in the United States...

Purpose Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the compleme...

Recent advances in the field of immuno‐oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the...

546 Background: Circadian rhythms regulate the cellular and molecular processes that determine treatment effects. Scarce data suggest that daily timing could influence endocrine therapy (ET) pharmacology. We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271) in patients (pts) with hormone receptors positiv...

Background: Poly(ADP-ribose) polymerase 1 inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA) in both the metastatic and adjuvant setting. Therefore, we need to reassess the frequency of gBRCA1 and gBRCA2 in order to redefi...

e17577 Background: PARP inhibitors (PARPi) demonstrated improvement in progression-free survival (PFS) following a first line platinum-based chemotherapy including bevacizumab for HRD-positive advanced ovarian carcinoma (OC) patients (pts) (PAOLA-1 study). We aimed to describe real-world (rw) clinical outcomes in patients with de novo high grade ep...

TPS2674 Background: Immunotherapy (IO) is increasingly used for treating various metastatic cancers. With respect to the pharmacologically-active levels of IO drugs and their pharmacokinetics features, standard scheduling lead to plasma exposures largely exceeding the thresholds associated with target engagement. Indeed, phase I studies have shown...

551 Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for...

e13639 Background: Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) that according to current evidence, can provide reliable information on the risk of recurrence but the knowledge regarding their real use in clinical practice is scarce. The PROCURE Project aims to establish recommendations on the...

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii...

Background Cancer patients (CPs) are considered more vulnerable and as a high mortality group regarding COVID-19. In this analysis, we aimed to describe asymptomatic COVID (+) CPs and associated factors. Methods We conducted a prospective study in CPs and health care workers (HCWs) in 4 French cancer centers (PAPESCO [ PAtients et PErsonnels de Sa...

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed dea...

MammaPrint® (MP) is a 70-gene signature that stratifies early-stage breast cancer patients into low- and high-risk of distant relapse. Further stratification of MP risk results identifies four risk subgroups, Ultra-Low (UL), Low, High 1 and High 2, with specific prognostic and predictive outcomes. BluePrint® (BP) is an 80-gene signature that classi...

Therapies that modulate immune response to cancer, such as immune checkpoint inhibitors, began an intense development a few years ago; however, in breast cancer (BC), the results have been relatively disappointing so far. Finding biomarkers for better selection of BC patients for various immunotherapies remains a significant unmet medical need. At...

Background: Cancer patients may fail to distinguish COVID-19 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, and fatigue, which are frequent after cancer treatments. We aimed to identify symptoms associated with COVID-19 and to assess the strength of their association in cancer and cancer-free populations. Methods: The multicenter...

e15537 Background: Inhibitors of tropomyosin receptor kinase (TRK) have shown promising activity against neurotrophic TRK ( NTRK) fusion-driven cancers, regardless of tumor histotype or cell of origin. NTRK gene fusions are observed in less than 1% of colorectal cancers (CRCs). CRCs harboring wild-type BRAF and KRAS and MisMatch Repair deficiency (...

Rationale The impact of the first COVID-19 wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. Patients, Material and Methods The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared to that during the same...

Aberrant activation of RET is a critical driver of growth and proliferation in diverse solid tumours. Multikinase inhibitors (MKIs) showing anti-RET activities have been tested in RET-altered tumours with variable results. The low target specificity with consequent increase in side-effects and off-target toxicities resulting in dose reduction and d...

Ki67 immunohistochemistry, commonly used as a proliferation marker in breast cancer, has limited value for treatment decisions due to questionable analytical validity. The International Ki67 Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 immunohistochemistry analytical validity and clinical util...

Ki67 immunohistochemistry, commonly used as a proliferation marker in breast cancer, has limited value for treatment decisions due to questionable analytical validity. The International Ki67 Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 immunohistochemistry analytical validity and clinical util...

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gen...

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in dia...

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management frame...

Aim There is no consensual indication for surgical resection after diagnosis on per-cutaneous biopsy of borderline breast lesions (B3). We evaluate under-evaluation rate of per-cutaneous biopsy and predictive factors of under-evaluation. We analyze accuracy of reported decision-making tools. Methods We conduct a prospective multicentric study incl...

Background: The nuclear proliferation biomarker Ki67 has multiple potential roles in breast cancer, including aiding decisions based on prognosis, but has unacceptable between-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) Assess inter-laboratory reproducibility of automa...

The advent of molecular biology resulted in the discovery of new oncogenes that have led to the development of targeted therapies for the management of cancer patients. The development of these therapies has improved the prognosis of patients in various tumour localizations. The TRK receptor (tropomyosin receptor kinase) is a transmembrane receptor...

The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 µM), combined with fractioned irradia...

Méthode de détection, localisation et quantification de protéines MDR Méthode in vitro de détection, de localisation et/ou de quantification de protéines de multirésistance aux médicaments (MDR) associées à des cellules, dans un échantillon contenant des cellules procaryotes ou eucaryotes exprimant ou susceptibles d’exprimer des protéines MDR. La m...

Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion pro...

Supplementary material was erroneously uploaded for this paper but the file was not intended for publication. This has now been removed.

The neurotrophic tyrosine receptor kinase ( NTRK ) gene family encodes three tropomyosin receptor kinases (TRKA, TRKB, TRKC) that contribute to central and peripheral nervous system development and function. NTRK gene fusions are oncogenic drivers of various adult and paediatric tumours. Several methods have been used to detect NTRK gene fusions in...

Aims The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of inter‐laboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic program to determine whether Ki67 measurement can be a...

Purpose The primary objective of this multicentric dose allocation and dose expansion study was to determine the MTD and the DLTs of the lucitanib (a tyrosine kinase inhibitor of the FGFR/VEGFR/PDFGR pathways)/fulvestrant combination. Methods Postmenopausal women with ER+/HER2− mBC, who have relapsed during or after treatment with fulvestrant, wer...

Résumé Alors que l’endométriose pelvienne est une pathologie fréquente, la transformation maligne des lésions endométriosiques, qui intéresse essentiellement les localisations ovariennes, reste très rare. Les mécanismes conduisant à cette évolution sont encore peu clairs. Les types histologiques les plus fréquemment observés sont l’adénocarcinome e...

Background The EndoPredict (EP) test has been developed and validated for assessing recurrence risk in patients with estrogen receptor (ER)-positive HER2-negative breast cancer (BC). This test is based on the expression of 12 genes (molecular score), combined with clinicopathological criteria ( tumor size and nodal status) (EPclin risk score). For...

Background The role of chemotherapy in early luminal breast cancer remains challenged. The NEOPAL trial (NCT 02400567; Cottu et al, ESMO 2017 LBA09) compared sequential chemotherapy (CT) and letrozole-palbociclib (LP) as neoadjuvant treatment in PAM50 defined high-risk luminal breast cancer patients, showing that LP might be as efficient as CT with...

Background: Durable responses of triple negative breast cancer (TNBC) to pembrolizumab (anti-PD-1) or atezolizumab (anti-PD-L1) have been reported in the metastatic setting. Moreover, it is currently being hypothesized that immune checkpoint inhibitors might be more effective in the neoadjuvant setting, due to better preserved anti-tumor immunity i...

Background: Therapeutic options at diagnosis for metastatic breast cancers (MBC) differ largely according to cancer phenotype (namely, hormone receptor (HR) and HER2 status). Reported discordance rates between primary tumor and metastasis vary widely in literature, with a median of 18% for estrogen receptor, 31% for progesterone receptor and 10% fo...

Background Several validated molecular subtyping tests for breast cancer based on gene expression profiling are now routinely used in clinical practice.The Prosigna® breast cancer (BC) prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurr...

Advanced Breast Cancer (ABC) comprises both locally advanced breast cancer (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains virtually an incurable disease with a median overall survival (OS) of 3 years and a 5-year survival of only 25% [2, 3]. The MBC Decade Report [2] shows that progress has been slow in terms of impr...

Background/aim: Genomic signatures are needed for the determination of prognosis in patients with early stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. EndoPredict test is a RNA-based multigene assay that assesses the risk of 10-year relapse in this context. Quality assessment is a m...

Background: Epidermal growth factor receptor (EGFR) is expressed in ˜50% of triple negative breast cancer (TNBC) and has been proposed as a therapeutic target in this disease. However, trials testing EGFR blockade in TNBC failed to show significant clinical benefit. Probable reasons for such results were patient selection based on EGFR expression a...

Background: Numerous studies have shown important impact of tumor-infiltrating lymphocytes (TILs) on natural or therapeutically-modified evolution of invasive breast cancer (IBC), however knowledge about TIL role in breast ductal carcinoma in situ (DCIS) is still limited. Because of the lack of reliable prognostic parameters, DCIS treatment is much...

FGFR1 amplification could mediate resistance to endocrine therapy and FGFR1 inhibition reverses this resistance. This phase Ib seeks to evaluate whether the combination of lucitanib, a potent FGFR/VEGFR/PDFGR inhibitor, in combination with fulvestrant, an endocrine agent, reverses resistance to fulvestrant. Eligible patients for this study were pos...

Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers, are very aggressive and with poor prognosis. Targeted therapies have been developed extensively in preclinical and clinical studies to open the way for new treatment strategies. The present study has focused on developing 3D cell cultures from SUM1315 and MDA-MB-231, two t...

Objectifs La marque épigénétique H3K27me3 et ses régulateurs, la méthyltransférase EZH2 et la déméthylase JMJD3 jouent un rôle important dans la progression tumorale prostatique. Le but de l’étude a été de déterminer le niveau transcriptionnel des gènes enrichis en H3K27me3 dans le cancer de la prostate et d’identifier l’impact de JMJD3 et d’EZH2 p...

The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer...

Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers, are very aggressive and with poor prognosis. Targeted therapies have been developed extensively in preclinical and clinical studies to open the way for new treatment strategies. The present study has focused on developing 3D cell cultures from SUM1315 and MDA-MB-231, two t...

e12592 Background: During last decade, therapeutic arsenal has expanded for metastatic breast cancer (mBC), but few data are available about mTNBC, a poor prognosis subtype. In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data...

Les cancers du sein sont subdivisés selon leur degré d’expression des récepteurs hormonaux et du gène HER2. La classification moléculaire a bouleversé cette conception simpliste en mettant en lumière de multiples profils de pronostics différents. C’est dans ce contexte, et devant la nécessité d’employer des traitements ciblés que sont nées les sign...

Background: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. Methods: Since 2011, a national network with a dedica...

In the original article, author F. Penault-Llorca's name was incorrectly written as F. Pernault-Llorca. This has been corrected online. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Background: HEV are specialized blood vessels that function as portals of entry for lymphocytes into lymphoid organs and tumor tissues (Moussion and Girard, Nature 2011, 479:542-546; Girard et al, Nature Rev Immunol 2012, 12:762-773). We retrospectively considered HEV and CD8 as potential prognostic and/or predictive factors in a large randomized a...

Background: The use of molecular tools for prognosis and prediction of CT benefit in EBC has increased the complexity of decision making. The 21-gene RS (Oncotype DX) is included in the ASCO (2007) and NCCN guidelines (2006) for prognosis (risk of distant recurrence [DR]) and prediction of CT benefit in N0, ER+ EBC. In 2015, the NCCN added that the...

Background: Recent molecular biology technologies reveals insight into tumor heterogeneity but quantification and impact on reproducibility of tests is not well known. The objective of this study was to assess the extent to which tumor heterogeneity may affect the prognosis of patients assessed by Prosigna™ (PAM50) gene signature assay compared to...

Background: Genomic tests can identify ER-positive Her2-negative localized breast cancer (BC) patients (pts) who may not drive any benefit from adjuvant chemotherapy (CT). Several genomic tests have reached a high level of analytical and clinical validity, as well as clinical utility in such situation. Recent results suggest that the safe de–escala...

The authors regret to misspell Dr F. Penault-Llorca's family name. The authors would like to apologise for any inconvenience caused.

Objectifs La méthyltransférase EZH2 et la déméthylase JMJD3 déterminent les niveaux de triméthylation de la lysine 27 de l’histone H3 (H3K27me3). Le rôle d’EZH2 dans la promotion et la progression tumorale prostatique a été largement étudié mais peu d’études impliquent JMJD3 dans ce cancer. L’objet de notre étude porte donc sur le rôle de JMJD3 dan...