Paul H Cottu

• MD, PhD
• Head of Department at Institut Curie

Objectives Sacituzumab govitecan, an anti-TROP2 antibody-drug conjugate, is approved for metastatic triple-negative breast cancer (TNBC) from the second-line setting and for hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer from the third line. Radiotherapy is frequently required in metastatic settings for symptom control, but its c...

Purpose: Meningeal carcinomatosis (MC) has a dismal prognosis in patients with breast cancer and requires invasive therapies. The aim of the present retrospective study was to determine a prognostic score for overall survival (OS) in patients with breast cancer and treated for MC. Methods: The data of 109 patients with proven breast cancer MC treat...

Pathological complete response (pCR) after neoadjuvant chemoimmunotherapy (NACi) is associated with improved patient outcomes in early triple-negative breast cancer (TNBC). This study aimed to identify factors associated with pCR after NACi. This cohort included all patients with stage II-III TNBC treated with NACi who underwent surgery at Institut...

Purpose To characterize real-world attrition rates across first-line (1L) to third-line (3L) therapies in patients with HER2-positive (HER2 +) metastatic breast cancer (mBC) receiving routine care in seven hospital systems across Europe (France, Germany, Italy, Spain, and the UK). Methods This retrospective, observational, multi-country, cohort st...

Background: The randomized, double-blind UNIRAD trial evaluating the addition of 2 years of everolimus to endocrine therapy in patients with high-risk, early luminal breast cancer failed to demonstrate a benefit. We report the subgroup analyses. Patients and Methods: We randomized 1278 patients in a 1:1 ratio to receive 2 years of placebo or everol...

Background Patients’ expectations regarding medical information in advanced stages of cancer are still poorly understood. Tailoring information to advanced cancer patients is a subtle task. We developed a question prompt list (QPL) that serves as a patient-oncologist communication aid in France. Methods A four-step sequential mixed method involvin...

Purpose Long-term treatment-related toxicities, such as neurologic and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities. Experimental Design Untargeted high-resolution metabolomic profiles of 992 patients with estrogen receptor (ER)+/HER2− breast cancer from the pr...

Objectives: In the recent MONALEESA-2, MONALEESA-3, and MONALEESA-7 clinical trials, the addition of ribociclib, a CDK4/6 inhibitor, to standard endocrine therapy significantly improved progression-free survival (PFS) compared with hormone therapy alone in the treatment of locally advanced or metastatic estrogen receptor-positive (ER) and HER2-neg...

PURPOSE Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS We used data from the...

PURPOSE Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC. METHODS Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 cent...

542 Background: We reported the benefit of taking evening tamoxifen compared to morning/afternoon as adjuvant treatment for high-risk breast cancers in the UNIRAD phase III trial (NCT01805271) (1). Here, we examine the relevance of EVE timing intake in this trial. Methods: 1,277 pts with high-risk HR+/ HER2- primary BC were randomly assigned to adj...

12122 Background: AIMT may lead to treatment discontinuation and detriment on clinical outcomes in pts with EBC. Recommended supportive care (SC) management include adequate physical activity (PA) levels, acupuncture, and physical therapy. Reasonable pharmacologic approaches include duloxetine use and switching AI. We assessed prevalence of AIMT, S...

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...

Paclitaxel is a first-line chemotherapy for hormone receptor positive (HR+) metastatic breast cancer patients after progression on a combination of endocrine and CDK4/6 inhibitor therapy. Response rate to paclitaxel ranges between 20-40%, and most patients progress due to intrinsic or acquired resistance, leaving them with limited treatment choices...

Background: Higher levels of pre and post-diagnosis physical exercise lead to reduced risk of death among survivors of BC. However, the effect of exercise on recurrence remains unclear. Furthermore, previous studies assumed a linear relationship between exercise and clinical outcomes, used discrete classifications of exercise and did not report res...

Background Peripheral neuropathy (PN) is a debilitating adverse event in patients with early breast cancer (BC) receiving (neo)adjuvant chemotherapy (CT). We harnessed the CANTO cohort study to detail clinical trajectories and explore clinical and genetic predictors of PN. Methods CANTO (CANcer TOxicities - NCT01993498) prospectively enrolled invas...

Background: Clonal hematopoiesis (CH) refers to the identification of clonal expansion of hematopoietic cells due to somatic mutations in leukemia-associated genes without evidence of hematologic anomalies. CH, particularly with variant allele frequency (VAF) ≥ 10%, has been associated with adverse outcomes, including reduced survival in advanced m...

Background: The Phase 2 PARSIFAL study assessed whether fulvestrant (FUL) or letrozole (LET) was the optimal endocrine partner for the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib (PAL) in patients (pts) with untreated, endocrine-sensitive, hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer (ABC) in the firs...

Background: Patients (pts) with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) who experience progression with adjuvant first-line (1L) therapy (trastuzumab, pertuzumab, and a taxane) typically require treatment escalation. Trastuzumab emtansine was standard of care in the second-line (2L) setting un...

Objective Previous studies showed that various outcomes in patients with early breast cancer (EBC), from incidence to survival, were influenced by social factors. However, there is limited research on the socioeconomic inequalities in quality of life (QoL) after treatment for EBC, and the magnitude and changes over time of these inequalities have n...

BACKGROUND: Previous studies suggested that bio-behavioral models explain part of the variability of cancer-related fatigue, and pro-inflammatory and age-related processes emerged as contributors to persistent fatigue. However, the biological underpinnings of this complex symptom, including its relevant genomic correlates, are still poorly understo...

Background The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal g...

Background Sacituzumab govitecan (SG) has been approved by FDA in April 2021 for pre-treated metastatic triple-negative breast cancer (mTNBC), following the ASCENT trial results. Methods We set up an ambispective bicentric cohort study to assess the real-world effectiveness and safety of SG in patients with mTNBC treated at Institut Curie Hospital...

Everolimus is widely used in patients with advanced ER‐positive, HER2‐negative breast cancer. We looked at alterations in the PIK3CA/AKT/mTOR pathway in a multicenter cohort as potential biomarkers of efficacy. Patients with advanced ER‐positive, HER2‐negative breast cancer treated with everolimus and endocrine therapy between 2012 and 2014 in two...

In a prospective study (NCT02866149), we assessed the efficacy of fulvestrant and everolimus in CDK4/6i pre-treated mBC patients and circulating tumor DNA (ctDNA) changes throughout therapy. Patients treated with fulvestrant and everolimus had their ctDNA assessed at baseline, after 3–5 weeks and at disease progression. Somatic mutations were ident...

Aims The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. Methods An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined...

Purpose Meningeal carcinomatosis carries a dismal prognosis in patients with breast cancer, and requires invasive therapies. The aim of the present retrospective study was to elaborate a prognostic score of overall survival in patients with breast cancer related meningeal carcinomatosis (MC). Methods 109 patients with proven breast cancer MC, trea...

Background Patients' expectations regarding medical information in advanced stages of cancer are still poorly understood in France. Tailoring information to advanced cancer patients is a subtle task. We have developed a question prompt list (QPL), serving as a patient-oncologist communication aid. Methods A four-step sequential mixed-method was fo...

Background: To identify patients most likely to respond to everolimus, a mammalian target of rapamycin (mTOR) inhibitor, a prospective biomarker study was conducted in hormone receptor-positive endocrine-resistant metastatic breast cancer patients treated with exemestane-everolimus therapy. Methods: Metastatic tumor biopsies were processed for i...

Importance Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition. Objective To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL). Design, Setting, and Participants The prospective, lon...

Purpose To determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab. Methods In this retrospective bicentric study, we included TNBC patients who underwent...

Purpose: This study assessed sustainable return to work (SRTW) of breast cancer survivors (BCS). Methods: We used data from the prospective French cohort, CANTO. We included 1811 stage I-III BCS who were <57 years old and employed at the moment of diagnosis and working 2 years after diagnosis. Using logistic regression, we investigated the role...

Skin reaction is a common toxicity during oncology management, especially followed during the radiotherapy. Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients treated for an early breast cancer (BC). We evaluated 8561 patients during their overall management for a BC. We focus...

Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients’ tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER...

Background: Many patients receiving adjuvant endocrine therapy (ET) for breast cancer experience side effects and reduced quality of life (QoL) and discontinue ET. We sought to describe these issues and develop a prediction model of early discontinuation of ET. Methods: Among patients with hormone receptor-positive and HER2-negative stage I-III...

The objective of the present study was to assess the outcomes and toxicity of patients treated with concurrent administration of CDK4/6 inhibitors (CDK4/6i) and locoregional radiation therapy (RT), including the breast with a boost or the thoracic wall after mastectomy and the regional lymph node areas. We retrospectively analyzed data from 27 pati...

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...

e13067 Background: Ribociclib is, for now, the only CDK4/6 inhibitor having demonstrated a statistically significant increase of overall survival in first-line in hormone receptor-positive, HER2-negative advanced breast cancer. One of the limiting toxicities of ribociclib is the occurrence of grade III/IV hepatobiliary toxicity in approximately 5%...

12081 Background: There is substantial inter individual variability in long-term trajectories of patient-reported quality of life (QOL) after early BC. Previous work focused on a selected group of patients (pts) treated with chemotherapy (CT) identified a cluster of pts with upfront poor QOL but also pts with severe, persistent post-chemotherapy QO...

Background: Early metastatic relapse of triple-negative breast cancer (mTNBC) after anthracyclins and/or taxanes based (A/T) primary treatment represents a highly aggressive cancer situation requiring urgent characterisation and handling. Epidemio-Strategy-Medico-Economical-Metastatic Breast Cancer (ESME-MBC) database, a multicenter, national, obs...

Introduction: The subcutaneous (H-SC) formulation of trastuzumab was demonstrated to be as effective and safe as intravenous (H-IV) and highly preferred by patients in early breast cancer. The present randomized MetaspHER trial (NCT01810393) has been the first study assessing patient's preference in metastatic setting and we report the final analy...

Objectives: We aimed to assess the impact of pharmacist interventions on injectable chemotherapy prescription and the safety of early prescription practice in an adult daily care unit. Methods: Prescription errors were recorded before and after implementing corrective measures. Errors identified from the pre-intervention period (i) were analysed...

The purpose of this study was to review the current knowledge regarding combinations of the most commonly used targeted therapies or those under development for the management of breast cancer with radiation therapy. Several studies have shown that the combination of radiation therapy and tamoxifen increased the risk of radiation-induced lung toxic...

Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of systems approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from altern...

Several clinical studies have shown that CDK4/6 inhibitors (CDK4/6i) improve survival in patients with metastatic or locally advanced HR-positive, HER-2-negative breast cancer (BC). The aim of this review was to synthesize the biological, preclinical and clinical aspects of the treatment of BC with CDK4/6i, with a focus on the combination of CDK4/6...

Purpose: We aimed to determine the pattern of isolated local recurrences (ILR) in women with stage II-III hormone receptor-positive and human epidermal growth factor receptor 2 breast cancer (HR + /HER2-BC) after 10-year follow-up. Methods: UNICANCER-PACS 01 and PACS 04 trials included 5,008 women with T1-T3 and N1-N3 to evaluate the efficacy of...

ctDNA as dynamic marker of response to fulvestrant and everolimus in CDK4/6 inhibitor-pretreated ER+ HER2- metastatic breast cancer patients: a prospective study. Background The combination of fulvestrant with everolimus is recognized by NCCN and ESMO guidelines as a valid second line treatment option for ER+ HER2- metastatic breast cancer (mBC), u...

Background Pembrolizumab (pembro, anti-PD-1 antibody) combined to chemotherapy (CT) in neoadjuvant/adjuvant setting has demonstrated its efficacy for early triple negative breast cancer (eTNBC). Pembro obtained FDA marketing authorization on July 26, 2021 and is available in France through the French Early Access Program. Methods We built an ambisp...

Background: Everolimus (EVE) addition to adjuvant hormonotherapy (HT) for high-risk early breast cancer (BC) did not improve 3-year disease-free survival (DFS) compared with ET alone in the randomized UNIRAD trial (NCT01805271) (1). Most patients (pts) withdrew from EVE for adverse events nearly midway before the expected treatment duration of 2 ye...

Simple Summary Everolimus is an oral drug used in patients with advanced hormone receptor positive, HER2 negative breast cancer. In this study based on a national French real-world cohort of more than 22,000 patients, we sought to evaluate the impact of everolimus on overall survival. Using statistical methods fit for real-world data, our findings...

Background The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose‐reductions (CDRs) or postchemotherapy‐toxicities (PCTs). Methods In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associat...

SOLAR-1 and BYLieve trials documented the efficacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CA-mutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients. We report here real-life datda of patients prospectively registered in the French alpelisib early access program (EAP) opened to PIK3CA-mutant HR...

Aims: High-grade metaplastic breast carcinoma (HG-MBC) is a rare subtype of invasive breast carcinoma, mostly triple-negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy and are associated with a worse outcome than invasive carcinomas of no special type. Methods: Clinicopathological characteristics and immunophenotype...

This review examined patterns of systemic anticancer treatment in patients with HR+/HER2− metastatic breast cancer in real-world clinical practice in Europe since 2016 to assess whether they reflect clinical guidelines and recent changes in available treatment options. We identified 30 publications for inclusion. In studies evaluating patients up t...

Background SOLAR-1 and BYLIEVE trials documented the efficacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CA-mutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients. We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP). Patients and m...

Importance ERBB2 -low (ie, ERBB2 immunohistochemistry score of 1+ or 2+ in the absence of ERBB2 gene amplification) breast cancer (BC) is a new entity, with emerging dedicated treatments. Little is known about its prognosis and response to conventional therapy compared with ERBB2 -zero breast tumors (ie, those with an immunohistochemistry score of...

Background We assessed the prevalence of self-reported perceived discrimination in the workplace after the end of treatment among breast cancer (BC) survivors and studied its association with social, health-related and work-related factors. Methods We used data from a French prospective cohort (CANcer TOxicities) including women diagnosed with sta...

Résumé Introduction Les urgences médicales sont définies sur un plan médical alors que le recours aux consultations d’urgence est décidé par l’usager. Le parcours médical oncologique en urgence est spécifique en raison de la complexité clinique, thérapeutique, technique et psychologique. Méthode Il s’agit d’une étude descriptive rétrospective de...

Background Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns of coffee and tea consumption and association with patient‐reported outcomes (PROs) and clinical outcomes among survivors of BC. Methods The authors...

Breast cancer is a frequent and sometimes fatal disease. The risk of locoregional recurrence has considerably decreased since the introduction of adjuvant treatments (radiotherapy, chemotherapy, hormone therapy). Nevertheless, some patients present a risk of multiple local recurrences. We report here the case of a patient who had four locoregional...

Skin damage is the most common and most important toxicity during and after radiation therapy (RT). Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients irradiated for an early breast cancer. CANTO is a prospective clinical cohort study of 10 150 patients with stage I‐III BC trea...

Background: Onapristone (ONA) is a progesterone receptor (PR) antagonist that prevents PR-mediated DNA transcription. ONA is currently being evaluated in metastatic breast cancers (MBC), as well as other hormone-dependent cancers. Recently, therapeutic options for metastatic estrogen receptor (ER) positive breast cancers have been expanded by the i...

Background: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear. Methods: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical a...

PURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor–resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PAT...

Purpose: We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors. Methods: Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498)...

Importance: Breast cancer (BC) diagnosis and treatment expose patients to a 5-fold higher risk of depression compared with the general population, with an estimated prevalence of 10% to 25%. A depressive episode in patients with BC has implications for the tolerance of and adherence to treatment, impairing quality of life and reducing life expecta...

PURPOSE Fatigue is recognized as one of the most burdensome and long-lasting adverse effects of cancer and cancer treatment. We aimed to characterize long-term fatigue trajectories among breast cancer survivors. METHODS We performed a detailed longitudinal analysis of fatigue using a large ongoing national prospective clinical study (CANcer TOxici...

Background Return to work (RTW) after cancer can be modulated by psychosocial factors, including a reordering of one’s life values, with more emphasis on private life than work-life. This change in patients’ outlook on work-life is however poorly understood. Methods We used data from a French cohort (CANTO, NCT01993498) of women diagnosed with sta...

Background Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention ai...

Purpose Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal...

Background Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, rand...

Long-term adherence to adjuvant endocrine therapy (ET, tamoxifen and aromatase inhibitors) is paramount for patients with early-stage breast cancer. Adherence to adjuvant endocrine therapy is hampered by numerous side effects associated with sustained estrogen deprivation. We aimed to describe recent real-world patterns of therapy, patients’ discon...

Background The everolimus (EVE)-exemestane combination has been included in the International guidelines for metastatic HR+/HER2- breast cancer (mBC) since the results of the Bolero-2 trial. Marketing authorization has been granted in France in July 2012. A first report of the UNICANCER Epidemiological Strategy and Medical Economics (ESME) Research...