Publications by authors named "Olivier Tredan"

108 Publications

Poly (ADP-ribose) polymerase inhibitors in combination with anti-angiogenic agents for the treatment of advanced ovarian cancer.

Future Oncol 2021 Mar 17. Epub 2021 Mar 17.

Department of Medical Oncology, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, Lyon, 69008, France.

Homologous recombination deficiency and VEGF expression are key pathways in high-grade ovarian cancer. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. The use of PARP inhibitors (PARPi) following chemotherapy has become standard of care in first line. Combination of PARPi with anti-angiogenic agents has demonstrated synergistic activity in preclinical study. This review summarizes the body of evidence supporting the efficacy and safety of the combination of PARPi and anti-angiogenic drugs in first-line homologous recombination deficiency high-grade ovarian cancer leading to US FDA and EMA approvals. This double maintenance is supported by: a large benefit with bevacizumab + olaparib compared with olaparib alone, a rationale for additive effect, and a good safety and cost-effective profile.
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http://dx.doi.org/10.2217/fon-2021-0059DOI Listing
March 2021

Investigation of circulating metabolites associated with breast cancer risk by untargeted metabolomics: a case-control study nested within the French E3N cohort.

Br J Cancer 2021 Mar 15. Epub 2021 Mar 15.

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health, Villejuif, France.

Background: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease.

Methods: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression.

Results: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women.

Conclusions: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.
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http://dx.doi.org/10.1038/s41416-021-01304-1DOI Listing
March 2021

Long-term patient reported outcomes and hematologic toxicity among patients who received Granulocyte-Colony Stimulating Factors during chemotherapy for early breast cancer.

Breast 2021 Mar 2;57:43-48. Epub 2021 Mar 2.

INSERM Unit 981 - Molecular predictors and new targets in oncology, Gustave Roussy, Villejuif, France. Electronic address:

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498). Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.27 [-0.33 to +2.87] and -1.01 [-1.98 to -0.04], respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time.
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http://dx.doi.org/10.1016/j.breast.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970125PMC
March 2021

Effects of an Exercise and Nutritional Intervention on Circulating Biomarkers and Metabolomic Profiling During Adjuvant Treatment for Localized Breast Cancer: Results From the PASAPAS Feasibility Randomized Controlled Trial.

Integr Cancer Ther 2021 Jan-Dec;20:1534735420977666

Léon Bérard Cancer Center, Lyon, France.

Purpose: Exercise has been shown to improve physical and psychological conditions during cancer therapy, but mechanisms remain poorly understood. The purpose of the present study was to report the results of cancer-related biomarkers and metabolomics outcomes from the PASAPAS feasibility study.

Methods: In the PASAPAS randomized controlled trial, 61 women beginning adjuvant chemotherapy for localized breast cancer were randomized in a 6-month program of weekly aerobic exercises associated with nutritional counseling versus usual care with nutritional counseling. In the present analysis of 58 women for whom blood samples were available, first, circulating levels of biomarkers (ie, insulin, insulin-like growth factor 1, estradiol, adiponectin, leptin, interleukin-6, and tumor necrosis factor α) were measured at baseline and 6-month follow-up. Changes in biomarkers were compared between exercisers (n = 40) and controls (n = 18) using mixed-effect models. Second, serum metabolites were studied using an untargeted H nuclear magnetic resonance spectroscopy, and orthogonal partial least squares analyses were performed to discriminate exercisers and controls at baseline and at 6 months.

Results: Over the 6-month intervention, no statistically significant differences were observed between exercisers and controls regarding changes in biomarkers and metabolomic profiles.

Conclusion: The present analysis of the PASAPAS feasibility trial did not reveal any improvement in circulating biomarkers nor identified metabolic signatures in exercisers versus controls during adjuvant breast cancer treatment. Larger studies preferably in women with poor physical activity level to avoid ceiling effect, testing different doses and types of exercise on additional biological pathways, could allow to clarify the mechanisms mediating beneficial effects of physical exercise during cancer treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT01331772. Registered 8 April 2011, https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1.
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http://dx.doi.org/10.1177/1534735420977666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934026PMC
March 2021

Prediction of Breast Cancer Treatment-Induced Fatigue by Machine Learning Using Genome-Wide Association Data.

JNCI Cancer Spectr 2020 Oct 11;4(5):pkaa039. Epub 2020 May 11.

Gustave Roussy, INSERM Unit 981, Villejuif, France.

Background: We aimed at predicting fatigue after breast cancer treatment using machine learning on clinical covariates and germline genome-wide data.

Methods: We accessed germline genome-wide data of 2799 early-stage breast cancer patients from the Cancer Toxicity study (NCT01993498). The primary endpoint was defined as scoring zero at diagnosis and higher than quartile 3 at 1 year after primary treatment completion on European Organization for Research and Treatment of Cancer quality-of-life questionnaires for Overall Fatigue and on the multidimensional questionnaire for Physical, Emotional, and Cognitive fatigue. First, we tested univariate associations of each endpoint with clinical variables and genome-wide variants. Then, using preselected clinical (false discovery rate < 0.05) and genomic ( < .001) variables, a multivariable preconditioned random-forest regression model was built and validated on a hold-out subset to predict fatigue. Gene set enrichment analysis identified key biological correlates (MetaCore). All statistical tests were 2-sided.

Results: Statistically significant clinical associations were found only with Emotional and Cognitive Fatigue, including receipt of chemotherapy, anxiety, and pain. Some single nucleotide polymorphisms had some degree of association ( < .001) with the different fatigue endpoints, although there were no genome-wide statistically significant ( < 5.00 × 10) associations. Only for Cognitive Fatigue, the predictive ability of the genomic multivariable model was statistically significantly better than random (area under the curve = 0.59,  = .01) and marginally improved with clinical variables (area under the curve = 0.60,  = .005). Single nucleotide polymorphisms found to be associated ( < .001) with Cognitive Fatigue belonged to genes linked to inflammation (false discovery rate adjusted  = .03), cognitive disorders ( = 1.51 × 10), and synaptic transmission ( = 6.28 × 10).

Conclusions: Genomic analyses in this large cohort of breast cancer survivors suggest a possible genetic role for severe Cognitive Fatigue that warrants further exploration.
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http://dx.doi.org/10.1093/jncics/pkaa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583150PMC
October 2020

Management and outcome of male metastatic breast cancer in the national multicenter observational research program Epidemiological Strategy and Medical Economics (ESME).

Ther Adv Med Oncol 2020 23;12:1758835920980548. Epub 2020 Dec 23.

Department of Medical Oncology, ICO Institut de Cancerologie de l'Ouest - René Gauducheau, Saint-Herblain, France.

Background And Aims: Because of its low prevalence, metastatic breast cancer (MBC) in males is managed based on clinical experience with women. Using a real-life database, we aim to provide a comprehensive analysis of male MBC characteristics, management and outcome.

Methods: The Epidemiological Strategy and Medical Economics Data Platform collected data for all men and women ⩾18 years with MBC in 18 participating French Comprehensive Cancer Centers from January 2008 to November 2016. Demographic, clinical, and pathological characteristics were retrieved, as was treatment modality. Men were matched 1:1 to women with similar characteristics.

Results: Of 16,701 evaluable patients, 149 (0.89%) men were identified. These men were older (median age 69 years) and predominantly had hormone receptor HR+/HER2- disease (78.3%). Median overall survival (OS) was 41.8 months [95% confidence interval (CI: 26.9-49.7)] and similar to women. Median progression-free survival (PFS) with first-line therapy was 9.3 months [95% CI (7.4-11.5)]. In the HR+/HER2- subpopulation, endocrine therapy (ET) alone was the frontline treatment for 43% of patients, including antiestrogens ( = 19), aromatase inhibitors ( = 15) with luteinizing hormone-releasing hormone (LHRH) analogs ( = 3), and various sequential treatments. Median PFS achieved by frontline ET alone was similar in men [9.8 months, 95% CI (6.9-17.4)] and in women [13 months, 95% CI (8.4-30.9)] ( = 0.80). PFS was similar for HR+/HER2- men receiving upfront ET or chemotherapy: 9.8 months [95% CI (6.9-17.4)] 9.5 months [95% CI (7.4-11.7)] ( = 0.22), respectively.

Conclusion: MBC management in men and women leads to similar outcomes, especially in HR+/HER2- patients for whom ET should also be a cornerstone. Unsolved questions remain and successfully recruiting trials for men are still lacking.
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http://dx.doi.org/10.1177/1758835920980548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768846PMC
December 2020

Molecular Characterization of Ovarian Yolk Sac Tumor (OYST).

Cancers (Basel) 2021 Jan 9;13(2). Epub 2021 Jan 9.

Centre Léon Berard (CLB), 69008 Lyon, France.

Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient's tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in , , . Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.
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http://dx.doi.org/10.3390/cancers13020220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826864PMC
January 2021

VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy-A Message from COMET, a French Unicancer Multicentric Study.

Pharmaceuticals (Basel) 2020 Nov 23;13(11). Epub 2020 Nov 23.

Medical Oncology Department, Institut Curie, St Cloud, 92210 Paris, France.

The prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and allow for a more personalized use of this antiangiogenic agent. To that end, we aimed to establish risk scores for survival prognosis dichotomization based on classic clinico-pathological criteria combined or not with single nucleotide polymorphisms (SNPs). The genomic DNA of 306 patients was extracted and a panel of 13 SNPs, covering seven genes previously documented to be potentially involved in drug response, were analyzed by means of high-throughput genotyping. In receiver operating characteristic (ROC) analyses, the hazard model based on a triple-negative cancer phenotype variable, combined with specific SNPs in (rs833061), (rs9582036) and (rs1870377), had the highest predictive value. The overall survival hazard ratio of patients assigned to the poor prognosis group based on this model was 3.21 (95% CI (2.33-4.42); < 0.001). We propose that combining this pharmacogenetic approach with classical clinico-pathological characteristics could markedly improve clinical decision-making for breast cancer patients receiving bevacizumab-based therapy.
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http://dx.doi.org/10.3390/ph13110414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700430PMC
November 2020

Brief Hospital Supervision of Exercise and Diet During Adjuvant Breast Cancer Therapy Is Not Enough to Relieve Fatigue: A Multicenter Randomized Controlled Trial.

Nutrients 2020 Oct 9;12(10). Epub 2020 Oct 9.

Oscar Lambret Center, 3 Rue Frédéric Combemale, 59000 Lille, France.

Supervised exercise dietary programs are recommended to relieve cancer-related fatigue and weight increase induced by adjuvant treatment of early breast cancer (EBC). As this recommendation lacks a high level of evidence, we designed a multicenter randomized trial to evaluate the impact of an Adapted Physical Activity Diet (APAD) education program on fatigue. We randomized 360 women with EBC who were receiving adjuvant chemotherapy and radiotherapy to APAD or usual care at eight French cancer institutions. Data were collected at baseline, end of chemotherapy, end of radiotherapy, and 6 months post-treatment. The primary endpoint was the general cancer-related fatigue score using the MFI-20 questionnaire. Fatigue correlated with the level of precariousness, but we found no significant difference between the two groups in terms of general fatigue ( = 0.274). The APAD arm has a smaller proportion of patients with confirmed depression at the end of follow-up ( = 0.052). A transient modification in physical activity levels and dietary intake was reported in the experimental arm. However, a mixed hospital- and home-based APAD education program is not enough to improve fatigue caused by adjuvant treatment of EBC. Cancer care centers should consider integrating more proactive diet-exercise supportive care in this population, focusing on precarious patients.
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http://dx.doi.org/10.3390/nu12103081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600233PMC
October 2020

Overcoming resistance to PARP inhibitor in epithelial ovarian cancer, are we ready?

EBioMedicine 2020 Nov 7;61:103046. Epub 2020 Oct 7.

Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, Lyon 69008, France.

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http://dx.doi.org/10.1016/j.ebiom.2020.103046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553990PMC
November 2020

Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial.

Transl Oncol 2020 Dec 18;13(12):100870. Epub 2020 Sep 18.

Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France. Electronic address:

Background: Advanced sarcoma is a group of heterogeneous disease with poor prognosis and poor efficacy of medical treatment. They represent a promising group of tumors to assess molecular-based therapy (MBT) strategy.

Patients And Methods: Genomic profiles of patients with advanced sarcoma included in the ProfiLER program were established by NGS using a 69 genes panel and CGH array. A weekly molecular board reviewed genomic reports to select relevant genomic alterations and propose recommendations for MBT.

Results: A genomic profile was available for 158 of 164 patients. At least 1 relevant genomic alteration was reported for 106 patients (67%), with frequent multiple alterations (68%). In total, 289 relevant genomic alterations were identified in 143 different genes; 139 homozygous deletions, 86 gene amplifications and 64 somatic mutations. The most frequently impacted genes were TP53, Rb1, CDKN2A, CDK4, MDM2, and PTEN. MBT was recommended for 47 patients and initiated for 13 patients. One objective response was observed for an angiosarcoma treated with pazopanib for FLT4 amplification; 4 patients had a stable disease, including a long-lasting 33 months stabilization.

Conclusion: Genomic profiling for advanced sarcoma is feasible, even for bone sarcoma. A small proportion of patients are eventually treated with MBT, similar to other tumor types. We could not demonstrate this strategy to be beneficial to patients. Our data suggest that molecular profiling should not be used in routine practice but warrants further exploration in clinical trials, focusing on sarcoma with complex genomic, and adding transcriptomic analysis to the copy number and mutational analyses.
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http://dx.doi.org/10.1016/j.tranon.2020.100870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509228PMC
December 2020

Design and methods of a national, multicenter, randomized and controlled trial to assess the efficacy of a physical activity program to improve health-related quality of life and reduce fatigue in women with metastatic breast cancer: ABLE02 trial.

BMC Cancer 2020 Jul 3;20(1):622. Epub 2020 Jul 3.

Department of Cancer and Environment, Léon Bérard Cancer Center, 28 rue Laennec, 69008, Lyon, France.

Background: Patients with a metastatic breast cancer suffer from a deteriorated health-related quality of life and numerous symptoms such as pain, severe fatigue and a decrease of their physical fitness. As the feasibility of a physical activity program has been demonstrated in this population, ABLE02 aims to assess the efficacy of a 6 month-physical activity program using connected devices to improve health-related quality of life and to reduce fatigue in women with metastatic breast cancer.

Methods: ABLE02 is a prospective, national, multicenter, randomized, controlled and open-label study. A total of 244 patients with a metastatic breast cancer, with at least one positive hormone receptor and a first-line chemotherapy planned, will be randomly assigned (1:1 ratio) to: (i) the intervention arm to receive physical activity recommendations, an activity tracker to wear 24 h a day during the whole intervention (6 months) with at least three weekly walking sessions and quizzes each week on physical activity and nutrition (ii) the control arm to receive physical activity recommendations only. Health-related quality of life will be assessed every 6 weeks and main assessments will be conducted at baseline, M3, M6, M12 and M18 to evaluate the clinical, physical, biological and psychological parameters and survival of participants. All questionnaires will be completed on a dedicated application.

Discussion: An activity program based on a smartphone application linked to an activity tracker may help to improve quality of life and reduce fatigue of patients with a metastatic breast cancer. The growth of e-health offers the opportunity to get real-time data as well as improving patient empowerment in order to change long-term behaviors.

Trial Registration: NCT number: NCT04354233 .
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http://dx.doi.org/10.1186/s12885-020-07093-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333295PMC
July 2020

Analysis of the StoRM cohort reveals physical activity to be associated with survival in metastatic breast cancer.

Sci Rep 2020 07 1;10(1):10757. Epub 2020 Jul 1.

Oncology Department, Centre Léon Bérard, Lyon, France.

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.
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http://dx.doi.org/10.1038/s41598-020-67431-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329808PMC
July 2020

Serum Detection of Nonadherence to Adjuvant Tamoxifen and Breast Cancer Recurrence Risk.

J Clin Oncol 2020 08 22;38(24):2762-2772. Epub 2020 Jun 22.

Institut Gustave Roussy, Villejuif, France.

Purpose: Nonadherence to long-term treatments is often under-recognized by physicians and there is no gold standard for its assessment. In breast cancer, nonadherence to tamoxifen therapy after surgery constitutes a major obstacle to optimal outcomes. We sought to evaluate the rate of biochemical nonadherence to adjuvant tamoxifen using serum assessment and to examine its effects on short-term, distant disease-free survival (DDFS).

Patients And Methods: We studied 1,177 premenopausal women enrolled in a large prospective study (CANTO/NCT01993498). Definition of biochemical nonadherence was based on a tamoxifen serum level < 60 ng/mL, assessed 1 year after prescription. Self-reported nonadherence to tamoxifen therapy was collected at the same time through semistructured interviews. Survival analyses were conducted using an inverse probability weighted Cox proportional hazards model, using a propensity score based on age, staging, surgery, chemotherapy, and center size.

Results: Serum assessment of tamoxifen identified 16.0% of patients (n = 188) below the set adherence threshold. Patient-reported rate of nonadherence was lower (12.3%). Of 188 patients who did not adhere to the tamoxifen prescription, 55% self-reported adherence to tamoxifen. After a median follow-up of 24.2 months since tamoxifen serum assessment, patients who were biochemically nonadherent had significantly shorter DDFS (for distant recurrence or death, adjusted hazard ratio, 2.31; 95% CI, 1.05 to 5.06; = .036), with 89.5% of patients alive without distant recurrence at 3 years in the nonadherent cohort versus 95.4% in the adherent cohort.

Conclusion: Therapeutic drug monitoring may be a useful method to promptly identify patients who do not take adjuvant tamoxifen as prescribed and are at risk for poorer outcomes. Targeted interventions facilitating patient adherence are needed and have the potential to improve short-term breast cancer outcomes.
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http://dx.doi.org/10.1200/JCO.19.01758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430219PMC
August 2020

High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR.

Eur J Cancer 2020 08 7;135:251-259. Epub 2020 Jun 7.

Centre Léon Bérard, 28 Rue Laënnec, 69373, Lyon Cedex 08, France; Université Claude Bernard Lyon I, France; Unicancer, Paris, France. Electronic address:

Background: Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated.

Methods: PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 real-time or reverse-transcriptase PCR (RT-PCR)-positive and RT-PCR-negative patients.

Results: Fifty-five of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR-positive patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of computed tomography (CT) scan. However, respectively, 38% and 20% of SARS-COV-2 RT-PCR-negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after the first symptoms, the death rate in RT-PCR-positive and RT-PCR-negative patients were 21% and 10%, respectively. In both groups, independent risk factors for death were male gender, Karnofsky performance status <60, cancer in relapse and respiratory symptoms. Detection of SARS-COV-2 on RT-PCR was not associated with an increased death rate (p = 0.10). None of the treatment given in the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2…) correlated with survival. The survival of RT-PCR-positive and -negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CT scan was similar with a 18.4% and 19.7% death rate at day 25. Most (22/30, 73%) cancer patients dying during this period were RT-PCR negative.

Conclusion: The 30-day death rate of cancer patients with or without documented SARS-COV-2 infection is poor, but the majority of deaths occur in RT-PCR-negative patients.
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http://dx.doi.org/10.1016/j.ejca.2020.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275994PMC
August 2020

ERα-36 regulates progesterone receptor activity in breast cancer.

Breast Cancer Res 2020 05 19;22(1):50. Epub 2020 May 19.

Université de Lyon, F-69000, Lyon, France.

Background: Alterations in estrogen and progesterone signaling, via their respective receptors, estrogen receptor alpha (ERα) and progesterone receptor (PR), respectively, are largely involved in the development of breast cancer (BC). The recent identification of ERα-36, a splice variant of ERα, has uncovered a new facet of this pathology. Although ERα-36 expression is associated with poor prognosis, metastasis development, and resistance to treatment, its predictive value has so far not been associated with a BC subtype and its mechanisms of action remain understudied.

Methods: To study ERα-36 expression in BC specimens, we performed immunochemical experiments. Next, the role of ERα-36 in progesterone signaling was investigated by generating KO clones using the CRISPR/CAS9 technology. PR signaling was also assessed by proximity ligation assay, Western blotting, RT-QPCR, and ChIP experiments. Finally, proliferation assays were performed with the IncuCyte technology and migration experiments using scratch assays.

Results: Here, we demonstrate that ERα-36 expression at the plasma membrane is correlated with a reduced disease-free survival in a cohort of 160 BC patients, particularly in PR-positive tumors, suggesting a crosstalk between ERα-36 and PR. Indeed, we show that ERα-36 interacts constitutively with PR in the nucleus of tumor cells. Moreover, it regulates PR expression and phosphorylation on key residues, impacting the biological effects of progesterone.

Conclusions: ERα-36 is thus a regulator of PR signaling, interfering with its transcriptional activity and progesterone-induced anti-proliferative effects as well as migratory capacity. Hence, ERα-36 may constitute a new prognostic marker as well as a potential target in PR-positive BC.
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http://dx.doi.org/10.1186/s13058-020-01278-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238515PMC
May 2020

[Effect of activities profile variations on health-related quality of life among breast cancer patients: Secondary exploratory analysis from PASAPAS study data].

Bull Cancer 2020 Jul - Aug;107(7-8):763-772. Epub 2020 May 13.

Centre Léon Bérard, département cancer environnement, 28, rue Laennec, 69008 Lyon, France; Centre de recherche en cancérologie de Lyon, UMR, Inserm 1052, CNRS 5286 CLB, 28, rue Laennec, 69008 Lyon, France.

Introduction: Lifestyle changes in breast cancer patients, by physical activity increasing, are becoming a main objective in supportive care. The objective of this study was to explore the impact of the daily activity profile evolution on the quality of life among this public.

Methods: Sixty patients (18 to 75 years) with non-metastatic breast cancer were randomized to a 2:1 ratio (physical activity intervention; control) in the PASAPAS randomized clinical trial. Multiple linear regression analyzes were computed to explain quality of life scores 6 months after the start of adjuvant therapy. Variables retained were the baseline quality of life scores, the anxiety trait, the randomization arm, the variations of time spent in different physical activity classes ([3-4 [MET, [4-6 [MET, ≥6 MET) and in sedentary behaviors.

Results: Only the decrease in time spent in sedentary behaviors really appeared as a predictor of the quality of physical life. Participation in the intervention group appeared as a predictor of quality of mental life.

Discussion: Results plead in favor of sedentary life style decrease as part of the objectives of care program for women with breast cancer. It also highlights the need of collective supervised sessions implemented by competent staff. This research also suggests that the dynamics of daily activity profile variations should be studied further in association to quality of life.
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http://dx.doi.org/10.1016/j.bulcan.2020.03.014DOI Listing
August 2020

Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

Sci Rep 2020 04 27;10(1):7073. Epub 2020 Apr 27.

Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.

BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44-0.90 for BRCA1; HR = 0.72; 95%CI, 0.47-1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40-1.1 for BRCA1; HR = 0.78; 95%CI, 0.44-1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28-0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11-1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21-0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11-1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.
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http://dx.doi.org/10.1038/s41598-020-63759-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184602PMC
April 2020

IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer.

Sci Immunol 2020 04 17;5(46). Epub 2020 Apr 17.

Univ Lyon, Université Claude Bernard Lyon 1, INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France.

Dendritic cells play a key role in the orchestration of antitumor immune responses. The cDC1 (conventional dendritic cell 1) subset has been shown to be essential for antitumor responses and response to immunotherapy, but its precise role in humans is largely unexplored. Using a multidisciplinary approach, we demonstrate that human cDC1 play an important role in the antitumor immune response through their capacity to produce type III interferon (IFN-λ). By analyzing a large cohort of breast primary tumors and public transcriptomic datasets, we observed specific production of IFN-λ1 by cDC1. In addition, both IFN-λ1 and its receptor were associated with favorable patient outcomes. We show that IFN-III promotes a T1 microenvironment through increased production of IL-12p70, IFN-γ, and cytotoxic lymphocyte-recruiting chemokines. Last, we showed that engagement of TLR3 is a therapeutic strategy to induce IFN-III production by tumor-associated cDC1. These data provide insight into potential IFN- or cDC1-targeting antitumor therapies.
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http://dx.doi.org/10.1126/sciimmunol.aav3942DOI Listing
April 2020

Rapalog-Mediated Repression of Tribbles Pseudokinase 3 Regulates Pre-mRNA Splicing.

Cancer Res 2020 06 3;80(11):2190-2203. Epub 2020 Apr 3.

Inserm, UMR981, Villejuif, France.

Rapalogs have become standard-of-care in patients with metastatic breast, kidney, and neuroendocrine cancers. Nevertheless, tumor escape occurs after several months in most patients, highlighting the need to understand mechanisms of resistance. Using a panel of cancer cell lines, we show that rapalogs downregulate the putative protein kinase TRIB3 (tribbles pseudokinase 3). Blood samples of a small cohort of patients with cancer treated with rapalogs confirmed downregulation of TRIB3. Downregulation of TRIB3 was mediated by LRRFIP1 independently of mTOR and disrupted its interaction with the spliceosome, where it participated in rapalog-induced deregulation of RNA splicing. Conversely, overexpression of TRIB3 in a panel of cancer cell lines abolished the cytotoxic effects of rapalogs. These findings identify TRIB3 as a key component of the spliceosome, whose repression contributes significantly to the mechanism of resistance to rapalog therapy. SIGNIFICANCE: Independent of mTOR signaling, rapalogs induce cytoxicity by dysregulating spliceosome function via repression of TRIB3, the loss of which may, in the long term, contribute to therapeutic resistance.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2366DOI Listing
June 2020

IMPDH1/YB-1 Positive Feedback Loop Assembles Cytoophidia and Represents a Therapeutic Target in Metastatic Tumors.

Mol Ther 2020 05 10;28(5):1299-1313. Epub 2020 Mar 10.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Recently, cytoophidium, a nonmembrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene Y-box binding protein 1 (YB-1) and served as an independent prognostic factor in ccRCC. Kaplan-Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.
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http://dx.doi.org/10.1016/j.ymthe.2020.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210706PMC
May 2020

Detailed overview on rare malignant ovarian tumors.

Bull Cancer 2020 Mar 27;107(3):385-390. Epub 2020 Feb 27.

Department of Medical Oncology, centre Léon-Bérard, University Claude Bernard (UCBL Lyon1), Lyon, France. Electronic address:

The group of rare malignant ovarian tumors includes the group of germ cell tumors, sex cords stromal ovarian tumors, small cell carcinoma, malignant Brenner tumors, rare epithelial tumors such as mucinous carcinoma, clear cell carcinoma, or low-grade serous carcinoma, as well as ovarian carcinosarcoma. Together they comprise about 10% of all ovarian tumors. Due to their low prevalence and their heterogeneity, data and treatment recommendations are limited. Even though all ovarian tumors are staged according to the FIGO staging of epithelial ovarian tumors, treatment differs especially in germ cell tumors and sex cords stromal ovarian tumors. Non-epithelial ovarian tumors can arise from a variety of ovarian precursor cells such as germ cells, granulosa cells, theca cells, or stromal fibroblasts. As can be expected already due to their divergent precursor lesions, these malignancies are substantially different but united by their rarity. This overview article gives a comprehensive summary on the pathology and clinical presentation, as well as therapy recommendations of a selection of those rare ovarian tumors, based on the latest national guidelines and related important publications.
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http://dx.doi.org/10.1016/j.bulcan.2020.01.011DOI Listing
March 2020

[Current advances in immunotherapy in ovarian cancer].

Bull Cancer 2020 Apr 20;107(4):465-473. Epub 2020 Feb 20.

Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France.

Ovarian cancers express highly immunogenic tissue-specific antigens. The resulting immune infiltration is a major prognostic factor. There is therefore a strong biological rationale for the development of immunotherapy in ovarian cancer. However, based on Phase I and II clinical trials data, the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors (ICPIs) remains limited in monotherapy in heavily pre-treated patients. Currently, the identification of predictive biomarkers of response and resistance is one of the major areas of research. Identifying effective combination of anti-PD-1 or anti-PD-L1 with other anticancer agents is another clinical need. Several combinations were evaluated. The association of ICPIs with chemotherapy (anthracyclines or carboplatin+paclitaxel) is disappointing (JAVELIN studies). The association with PARP inhibitors, anti-angiogenic agents and CTLA-4 inhibitors seems promising. Other immune therapies such as cell therapies (adoptive transfer of intra-tumor lymphocytes, CAR T cells or vaccines from dendritic cells) could be the future of immunotherapy in ovarian cancer but only early phase studies clinical data is available at this time.
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http://dx.doi.org/10.1016/j.bulcan.2019.11.015DOI Listing
April 2020

CD163 tumor-associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes.

Clin Transl Immunology 2020 13;9(2):e1108. Epub 2020 Feb 13.

INSERM U1052 CNRS 5286 Centre Léon Bérard Centre de Recherche en Cancérologie de Lyon Univ Lyon Université Claude Bernard Lyon 1 Lyon France.

Objectives: The accumulation of tumor-associated macrophages (TAMs) is correlated with poor clinical outcome, but the mechanisms governing their differentiation from circulating monocytes remain unclear in humans.

Methods: Using multicolor flow cytometry, we evaluated TAMs phenotype in 93 breast cancer (BC) patients. Furthermore, monocytes from healthy donors were cultured in the presence of supernatants from dilacerated primary tumors to investigate their differentiation into macrophages (MΦ) . Additionally, we used transcriptomic analysis to evaluate BC patients' blood monocytes profiles.

Results: We observed that high intra-tumor CD163-expressing TAM density is predictive of reduced survival in BC patients. , M-CSF, TGF-β and VEGF from primary tumor supernatants skewed the differentiation of healthy donor blood monocytes towards CD163CD86IL-10 M2-like MΦ that strongly suppressed CD4 T-cell expansion PD-L1 and IL-10. In addition, blood monocytes from about 40% of BC patients displayed an altered response to stimulation, being refractory to type-1 MΦ (M1-MΦ) differentiation and secreting higher amounts of immunosuppressive, metastatic-related and angiogenic cytokines. Aside from showing that monocyte transcriptome is significantly altered by the presence of BC, we also demonstrated an overall metabolic de-activation in refractory monocytes of BC patients. In contrast, monocytes from sensitive BC patients undergoing normal M1-MΦ differentiation showed up-regulation of IFN-response genes and had no signs of metabolic alteration.

Conclusion: Altogether, our results suggest that systemic factors skew BC patient blood monocytes towards a pro-metastatic profile, resulting in the accumulation of further polarised CD163 TAMs resembling type-2 MΦ (M2-MΦ) in the local BC microenvironment. These data indicate that monitoring circulating monocytes in BC patients may provide an indication of early systemic alterations induced by cancer and, thus, be instrumental in the development of improved personalised immunotherapeutic interventions.
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http://dx.doi.org/10.1002/cti2.1108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017151PMC
February 2020

The fully synthetic glycopeptide MAG-Tn3 therapeutic vaccine induces tumor-specific cytotoxic antibodies in breast cancer patients.

Cancer Immunol Immunother 2020 May 7;69(5):703-716. Epub 2020 Feb 7.

Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, 28 rue du Dr Roux, 75015, Paris, France.

Cancer is one of the main causes of mortality worldwide and a major public health concern. Among various strategies, therapeutic vaccines have been developed to stimulate anti-tumoral immune responses. However, in spite of extensive studies, this approach suffers from a lack of efficacy. Recently, we designed the MAG-Tn3 vaccine, aiming to induce antibody responses against Tn, a tumor-associated carbohydrate antigen. The Tn antigen is of interest because it is expressed by several adenocarcinomas, but not normal cells. The fully synthetic glycopeptide vaccine MAG-Tn3 is composed of four arms built on three adjacent Tn moieties associated with the tetanus toxin-derived peptide TT CD4 T-cell epitope. This promiscuous CD4 T-cell epitope can bind to a wide range of HLA-DRB molecules and is thus expected to activate CD4 T-cell responses in a large part of the human population. The MAG-Tn3 vaccine was formulated with the GSK-proprietary immunostimulant AS15, composed of CpG7909, MPL, and QS21, which has been shown to stimulate both innate and humoral responses, in addition to being well tolerated. Here, seven patients with localized breast cancer with a high-risk of relapse were immunized with the MAG-Tn3 vaccine formulated with AS15. The first results of phase I clinical trial demonstrated that all vaccinated patients developed high levels of Tn-specific antibodies. Moreover, these antibodies specifically recognized Tn-expressing human tumor cells and killed them through a complement-dependent cytotoxicity mechanism. Overall, this study establishes, for the first time, the capacity of a fully synthetic glycopeptide cancer vaccine to induce specific immune responses in humans.
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http://dx.doi.org/10.1007/s00262-020-02503-0DOI Listing
May 2020

Feasibility and Health Benefits of an Individualized Physical Activity Intervention in Women With Metastatic Breast Cancer: Intervention Study.

JMIR Mhealth Uhealth 2020 01 28;8(1):e12306. Epub 2020 Jan 28.

Department of Cancer and Environment, Léon Bérard Cancer Center, Lyon, France.

Background: There is limited knowledge regarding the potential benefits of physical activity in patients with metastatic breast cancer.

Objective: The Advanced stage Breast cancer and Lifestyle Exercise (ABLE) Trial aimed to assess the feasibility of a physical activity intervention in women with metastatic breast cancer and to explore the effects of physical activity on functional, psychological, and clinical parameters.

Methods: The ABLE Trial was a single-arm, 6-month intervention study with a home-based, unsupervised, and personalized walking program using an activity tracker. At baseline and 6 months, we assessed anthropometrics, functional fitness, physical activity level, sedentary behavior, quality of life, fatigue, and tumor progression. Paired proportions were compared using the McNemar test and changes of parameters during the intervention were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney test, and Spearman rank correlations.

Results: Overall, 49 participants (mean age 55 years; recruitment rate 94%) were enrolled and 96% adhered to the exercise prescription (attrition rate 2%). Statistically significant improvements in the 6-minute walking distance test (+7%, P<.001) and isometric quadriceps strength (+22%, P<.001), as well as decreases in body mass index (-2.5%, P=.03) and hip circumference (-4.0%, P<.001) were observed at 6 months. Quality of life remained stable and a nonstatistically significant decrease (-16%, P=.07) in fatigue was observed.

Conclusions: The high recruitment and adherence rates suggest the willingness of patients with metastatic breast cancer to participate in a physical activity program. The beneficial outcomes regarding physical fitness and anthropometry of this unsupervised physical activity program may encourage these patients to maintain a physically active lifestyle. Future randomized controlled trials with larger sample sizes are warranted.

Trial Registration: ClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886.
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http://dx.doi.org/10.2196/12306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013652PMC
January 2020

The quality of life of long-term remission patients in the Vivrovaire study: The impact of ovarian cancer on patient trajectory.

J Psychosoc Oncol 2020 Jul-Aug;38(4):481-500. Epub 2020 Jan 28.

GRePS, Lyon 2 University, Lyon, France.

In this study, we explored how ovarian cancer (OC) survivors give meaning to their cancer experience and how the latter has an impact on their quality of life (QOL). The sample comprised 16 OC patients participating in the French study Vivrovaire in Lyon who were in long-term remission. We employed a qualitative approach, based on semi-structured interviews. Using ATLAS.ti software, we performed a thematic analysis of the collected data. Three main OC-related themes emerged: body and physical issues; social life evolutions; participant retrospective perception of OC experience. Our results underline the need to take into account the various dimensions of patient identity when studying OC survivors' QOL and to consider intra-individual QOL evolutions from a temporal perspective. Helping patients acquire a sound understanding of their illness experience is an enormous challenge for OC healthcare.
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http://dx.doi.org/10.1080/07347332.2019.1710656DOI Listing
January 2020

Impact of Breast Cancer Treatment on Employment: Results of a Multicenter Prospective Cohort Study (CANTO).

J Clin Oncol 2020 03 13;38(7):734-743. Epub 2019 Dec 13.

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.

Purpose: Adverse effects of breast cancer treatment can negatively affect survivors' work ability. Previous reports lacked detailed clinical data or health-related patient-reported outcomes (PROs) and did not prospectively assess the combined impact of treatment and related sequelae on employment.

Methods: We used a French prospective clinical cohort of patients with stage I-III breast cancer including 1,874 women who were working and ≥ 5 years younger than legal retirement age (≤ 57 years) at breast cancer diagnosis. Our outcome was nonreturn to work (non-RTW) 2 years after diagnosis. Independent variables included treatment characteristics as well as toxicities (Common Toxicity Criteria Adverse Events [CTCAE] v4) and PROs (European Organization for Research and Treatment of Cancer [EORTC] Quality of life Questionnaires, Breast cancer module [QLQ-BR23] and Fatigue module [QLQ-FA12], Hospital Anxiety and Depression Scale) collected 1 year after diagnosis. Logistic regression models assessed correlates of non-RTW, adjusting for age, stage, comorbidities, and socioeconomic covariates.

Results: Two years after diagnosis, 21% of patients had not returned to work. Odds of non-RTW were significantly increased among patients treated with combinations of chemotherapy and trastuzumab (odds ratio [OR] chemotherapy-hormonotherapy: for chemotherapy-trastuzumab, 2.01; 95% CI, 1.18 to 3.44; for chemotherapy-trastuzumab-hormonotherapy, 1.62; 95% CI, 1.10 to 2.41). Other significant associations with non-RTW included grade ≥ 3 CTCAE toxicities (OR no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR no, 2.29; 95% CI, 1.34 to 3.91).

Conclusion: Receipt of systemic therapy combinations including trastuzumab was associated with increased odds of non-RTW. Likelihood of unemployment was also higher among patients who reported severe physical and psychological symptoms. This comprehensive study identifies potentially vulnerable patients and warrants supportive interventional strategies to facilitate their RTW.
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http://dx.doi.org/10.1200/JCO.19.01726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048162PMC
March 2020

Prognostic value of CEC count in HER2-negative metastatic breast cancer patients treated with bevacizumab and chemotherapy: a prospective validation study (UCBG COMET).

Angiogenesis 2020 05 26;23(2):193-202. Epub 2019 Nov 26.

Department of Medical Oncology, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005, Paris & Saint Cloud, France.

Background: Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757).

Methods: The main baseline criteria were HER2-negative mBC, performance status 0-2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS).

Results: CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0-2231). Baseline CEC counts were associated with performance status (p = 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous: p < 0.001; dichotomized: HR 1.52, 95% CI [1.15-2.02], p = 0.004). CEC counts at 4 weeks had no prognostic impact.

Conclusion: This study confirms that CEC count may be associated with the outcome of mBC patients treated with chemotherapy and bevacizumab. However, discrepancies with previous reports in terms of both the timing of CEC count and the direction of the prognostic impact warrant further clinical investigation.
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http://dx.doi.org/10.1007/s10456-019-09697-7DOI Listing
May 2020