Publications by authors named "Roman Rouzier"

284 Publications

F-FDG PET/CT in Relapsed Endometrial Cancer Treated with Preoperative PD-1 Inhibitor Dostarlimab.

Diagnostics (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Department of Nuclear Medicine and Endocrine Oncology, Institut Curie, 92210 Saint-Cloud, France.

Dostarlimab is an immune checkpoint inhibitor (ICI) targeting the Programmed-Death-1 (PD-1) co-receptor, recently approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) as a novel therapy for recurrent or advanced endometrial cancer. We report the case of a 64-year-old woman, experiencing vaginal recurrence with microsatellite instability high/hypermutated of a FIGO stage IA grade 2 endometrial endometrioid adenocarcinoma. She received preoperative chemotherapy with four cycles of carboplatin plus paclitaxel, with stable disease on pelvic magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG PET/CT). Dostarlimab (500 mg intravenously every 3 weeks) was then introduced. The subsequent evaluation after three perfusions demonstrated a complete metabolic response on F-FDG PET/CT according to immunotherapy-modified PET response criteria in solid tumors (imPERCIST) criteria, then confirmed by MRI according to immune response evaluation criteria in solid tumors (iRECIST). This clinical description suggests that F-FDG PET/CT might take place among available tools for guiding the preoperative management for recurrent endometrial cancer patients receiving dostarlimab immunotherapy that should be further explored through clinical trials.
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http://dx.doi.org/10.3390/diagnostics11081353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391233PMC
July 2021

Human papillomavirus (HPV) vaccine coverage rates (VCRs) in France: A French claims data study.

Vaccine 2021 08 30;39(36):5129-5137. Epub 2021 Jul 30.

University Hospital of Strasbourg and EA3181, University of Bourgogne Franche-Comte, Besançon, France.

Background: The French Cancer Plan 2014-2019 had a target of 60% HPV vaccine coverage. The PAPILLON study investigated the annual age-specific vaccination initiation rates and cumulative partial and complete vaccination rates in France from 2017 to 2022. It also identified the factors associated with vaccination in different age groups and those associated with the type of completion of the vaccination scheme (partial vs full vaccination).

Methods: For this publication, all females recorded in the French National Claims database who initiated HPV vaccination between 1 July 2007 and 31 December 2018 and were aged between 11 and 19 years at initiation were included. Annual HPV vaccination initiation rates were estimated in 11- to 14-year-old (target population) and 15- to 19-year-old females (catch-up). Cumulative vaccine coverage rates (VCRs) were estimated among those who were 15, 16, 20 and 21 years old. Partial vaccination was defined by dispensing of at least one dose of HPV vaccine by the pharmacy, while full vaccination was defined by two or three doses dispensed by a pharmacy over an 18-month period, according to current French recommendations based on the age at vaccination initiation.

Results: Among the 465,629 females who initiated HPV vaccination in 2017 or 2018, the initiation rate increased from 7.7 to 11.1% in 11- to 14-year-old girls and from 4.5 to 6.5% in 15- to 19-year-old females. In 2017 and 2018, the cumulative VCRs for partial vaccination by age 15 were 28.2% and 32.8%, respectively, while by age 20, they were 41.6% and 38.8%. The cumulative VCRs for full vaccination were 15.6% and 18.6% by age 16, while they were 25.9 and 23.6% by age 20. HPV vaccination initiation and completion were strongly associated with the use of health services.

Conclusion: Overall, the HPV VCR substantively increased between 2017 and 2018, which is positive evidence of the resumption of vaccination. Updates in 2022 should confirm these results.
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http://dx.doi.org/10.1016/j.vaccine.2021.07.054DOI Listing
August 2021

Clinicopathological characterization of a real-world multicenter cohort of endometrioid ovarian carcinoma: Analysis of the French national ESME-Unicancer database.

Gynecol Oncol 2021 Jul 19. Epub 2021 Jul 19.

Aix-Marseille Univ., CNRS, INSERM, Institut Paoli-Calmettes, Department of Medical Oncology, CRCM, Marseille, France. Electronic address:

Background: Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes.

Methods: We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features.

Results: Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p < 0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p < 0.001).

Conclusions: Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.019DOI Listing
July 2021

Has tumor doubling time in breast cancer changed over the past 80 years? A systematic review.

Cancer Med 2021 Aug 15;10(15):5203-5217. Epub 2021 Jul 15.

Department of Surgery, Institut Curie Hospital Group, Saint-Cloud, France.

Over the past century, epidemiologic changes and implementation of screening may have had an impact on tumor doubling time in breast cancer. Our study was designed to evaluate changes in tumor doubling time in breast cancer over the past 80 years. A systematic review of published literature and meta-regression analysis was performed. An online electronic database search was undertaken using the PubMed platform from inception until June 2020. All studies that measured tumor doubling time in breast cancer were included. A total of 151 publications were retrieved. Among them, 16 full-text articles were included in the qualitative analysis. An exponential growth model was used for quantitative characterization of tumor growth rate. Tumor doubling time has remained stable over the past 80 years. Recent studies have not only identified "fast growing tumor" (grade 3, human epidermal growth factor receptor 2-positive, triple-negative, or tumor with an elevated Ki-67) but also "inactive breast cancer" feeding the ongoing debate of overdiagnosis due to screening programs. The stability of tumor doubling time over the past 80 years, despite increasing and changing risk factors, supports the validity for our screening guidelines. Prospective studies based on more precise measurement of tumor size and adjustment for tumor characteristics are necessary to more clearly characterize the prognostic and predictive impact of tumor doubling time in breast cancer.
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http://dx.doi.org/10.1002/cam4.3939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335823PMC
August 2021

Circulating HPV DNA as a marker for early detection of relapse in patients with cervical cancer.

Clin Cancer Res 2021 Jul 1. Epub 2021 Jul 1.

Institute Curie.

Purpose: Almost all cervical cancers (CC) are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemo-radiation or to predict relapse during the follow-up period.

Experimental Design: We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV gene as a marker for residual disease compared to HPV integration site and mutations. Finally, the prognostic impact of circulating HPV gene was assessed with its prediction value of relapse.

Results: HPV gene was the most sensitive tumor marker, superior to both HPV integration sites and mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (p=0.02) and para-aortic lymph node involvement (p=0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R=0.39, p<0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (p<0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection.

Conclusions: HPV ctDNA detection is a useful marker to predict relapse in CC.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0625DOI Listing
July 2021

Laparoscopic perineal hernia repair following pelvic exenteration: a case report.

BMC Surg 2021 May 18;21(1):245. Epub 2021 May 18.

Département d'oncologie Chirurgicale, Institut Curie, PSL Research University, 35, Rue Dailly, 92210, Saint-Cloud, France.

Background: Acquired perineal hernia is a rare complication following extensive pelvic surgery. Radiotherapy is also a predisposing factor. Perineal hernia can cause chronic perineal pain, bowel obstruction, urinary disorders and a cosmetically disfiguring defect. The treatment of perineal hernia is surgical, usually consisting of mesh repair via an abdominal or perineal approach.

Case Presentation: We present a case report and a surgical video of a 42-year-old woman with history of a squamous cell carcinoma. This patient had 3 recurrences since the diagnosis and a symptomatic perineal hernia. Complete regression of the recurrent malignancy allowed us to treat the perineal hernia. We performed laparoscopic repair with prosthetic mesh in this patient who had undergone multiple surgeries and radiotherapy, while preserving the omental flap that was used to reconstruct the posterior part of the vagina.

Conclusion: There is no consensus concerning the preferred surgical approach, perineal or laparoscopic, as no study has demonstrated the superiority of either of these approaches. Laparoscopic repair for an acquired perineal hernia is safe and feasible. However, further studies including randomized trials are required to precisely evaluate the best surgical approach and type of mesh.
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http://dx.doi.org/10.1186/s12893-021-01237-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132409PMC
May 2021

Adherence to French and ESGO Quality Indicators in Ovarian Cancer Surgery: An Ad-Hoc Analysis from the Prospective Multicentric CURSOC Study.

Cancers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Department of Gynecologic Oncology, Agostino Gemelli University Hospital, 00168 Rome, Italy.

Background: Quality Indicators for ovarian cancer (OC) have been developed by the European Society of Gynaecological Oncology (ESGO) and by the French National Cancer Institute (Institut National du Cancer, INCa). The aim of the study was to characterize OC care distribution in France by case-volume and to prospectively evaluate the adherence of high-volume institutions to INCa/ESGO quality indicators.

Methods: The cost-utility of radical surgery in ovarian cancer (CURSOC) trial is a prospective, multicenter, comparative and non-randomized study that includes patients with stage IIIC-IV epithelial OC treated in nine French health care tertiary institutions. Adherence to institutional quality indicators were anonymously assessed by an independent committee. OC care distribution in France were provided by the nationwide database of hospital procedures.

Results: More than half of patients are treated in low-volume institutions. Among the nine high-volume centers participating in the study, four (44.4%) met all institutional INCa/ESGO quality indicators. The other five (55.6%) did not fulfil one of the quality indicator criteria.

Conclusions: Access to high-volume OC providers in France is restricted to a minority of patients, and yet half of the referral institutions included in this study failed to meet all recommended institutional quality indicators. It is mandatory that national authorities work both to improve OC centralization and to incorporate quality assurance programs into certified centers.
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http://dx.doi.org/10.3390/cancers13071593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037412PMC
March 2021

Total metabolic tumor volume and spleen metabolism on baseline [18F]-FDG PET/CT as independent prognostic biomarkers of recurrence in resected breast cancer.

Eur J Nucl Med Mol Imaging 2021 Oct 27;48(11):3560-3570. Epub 2021 Mar 27.

Department of Nuclear Medicine, Institut Curie, 92210, Saint-Cloud, France.

Purpose: We evaluated whether biomarkers on baseline [F]-FDG PET/CT are associated with recurrence after surgery in patients with invasive breast cancer of no special type (NST).

Methods: In this retrospective single-center study, we included consecutive patients with non-metastatic breast cancer of NST who underwent [F]-FDG PET/CT before treatment, including surgery, between 2011 and 2016. Clinicopathological data were collected. Tumor SUVmax, total metabolic tumor volume (TMTV), and spleen- and bone marrow-to-liver SUVmax ratios (SLR, BLR) were measured from the PET images. Cut-off values were determined using predictiveness curves to predict 5-year recurrence-free survival (5y-RFS). A multivariable prediction model was developed using Cox regression. The association with stromal tumor-infiltrating lymphocytes (TILs) levels (low if <50%) was studied by logistic regression.

Results: Three hundred and three women were eligible, including 93 (31%) with triple-negative breast carcinoma. After a median follow-up of 6.2 years, 56 and 35 patients experienced recurrence and death, respectively. The 5y-RFS rate was 86%. In multivariable analyses, high TMTV (>20 cm3) and high SLR (>0.76) were associated with shorter 5y-RFS (HR 2.4, 95%CI 1.3-4.5, and HR 1.9, 95%CI 1.0-3.6). In logistic regression, high SLR was the only independent factor associated with low stromal TILs (OR 2.8, 95%CI 1.4-5.7).

Conclusion: High total metabolic tumor volume and high spleen glucose metabolism on baseline [F]-FDG PET/CT were associated with poor 5y-RFS after surgical resection in patients with breast cancer of NST. Spleen metabolism was inversely correlated with stromal TILs and might be a surrogate for an immunosuppressive tumor microenvironment.
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http://dx.doi.org/10.1007/s00259-021-05322-2DOI Listing
October 2021

Correlation of ultrasound, cytological, and histological features of 110 benign BI-RADS categories 4C and 5 nonpalpable breast lesions. The Institut Curie's experience.

Cancer Cytopathol 2021 06 10;129(6):479-488. Epub 2021 Mar 10.

Department of Diagnostic and Theragnostic Biology, Institut Curie, Paris, France.

Background: The purpose of this study was to determine the pathological and ultrasound (US) features of benign nonpalpable breast lesions (NPBLs) classified as Breast Imaging Reporting and Data System (BI-RADS) category 4C or 5.

Methods: Between 2003 and 2007, 849 consecutive NPBLs detected at US and classified as BI-RADS category 4C (505) or 5 (344) initially underwent US-guided fine needle aspiration (FNA) at our institution. Benign diagnoses were established according to surgical excision findings or during a minimal 6-month imaging follow-up (mean, 3.7 years [SD, 2.6 years]). US BI-RADS features were reviewed and compared retrospectively using a chi-square test for the following pathological categories: epithelial and fibrous proliferation (EFP), cystic and papillary lesion (C&P), inflammatory lesion (IL), benign tumor (BT), intramammary lymph node (ILN), intraepithelial proliferative lesion (IPL), and nonspecific morphological alteration (NMA). The performance of FNA in the diagnosis of benignity was assessed.

Results: Of 849 NPBLs, 110 (12.9%) NPBLs were benign: 88 (17.4%) were BI-RADS category 4C, and 22 (6.4%) were BI-RADS category 5. Forty-four (40%) were EFPs, 21 (19%) were C&Ps, 13 (12%) were NMAs, 11 (10%) were ILs, 11 (10%) were BTs, 8 (7%) were IPLs, and 2 (2%) were ILNs. Lesion shape, US pattern distribution, and posterior features showed statistically significant differences between these categories (P < .05): 33 (75%) EFPs exhibited posterior shadowing, 18 (86%) C&Ps were homogenous, 9 (82%) ILs were heterogeneous, 11 (100%) BTs were homogeneous, 9 (82%) BTs were oval, and 6 (75%) IPLs were irregularly shaped. Of the 110 benign NPBLs, FNA diagnosis was falsely positive in 7 (6%), suspicious in 10 (9%), and benign in 90 (82%), and 3 (3%) were inadequate for diagnosis.

Conclusion: A diverse array of benign NPBLs can be classified as BI-RADS category 4C or 5 on US, each showing specific imaging presentations.
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http://dx.doi.org/10.1002/cncy.22402DOI Listing
June 2021

Real-life prognosis of 5041 bone-only metastatic breast cancer patients in the multicenter national observational ESME program.

Ther Adv Med Oncol 2021 21;13:1758835920987657. Epub 2021 Jan 21.

Department of Medical Oncology, ICO René Gauducheau, Boulevard Jacques Monod, Saint Herblain, Pays de la Loire 44805, France.

Background: Bone-only (BO) metastatic breast cancer (MBC) is considered a more favorable entity than other MBC presentations. However, only few retrospective series and data from selected randomized controlled trials have been reported so far.

Methods: Using the French national multicenter ESME (Epidemiological Strategy and Medico Economics) Data Platform, the primary objective of our study was to compare the overall survival (OS) of patients with BO non-BO MBC at diagnosis, with adjustment on main prognostic factors using a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1), describe treatment patterns, and estimate factors associated with OS.

Results: Out of 20,095 eligible women, 5041 (22.4%) patients had BO disease [hormone-receptor positive (HR+)/human epidermal growth-factor-receptor-2 negative (HER2-),  = 4 102/13,229 (31%); HER2+,  = 644/3909 (16.5%); HR-/HER2-,  = 295/2 957 (10%)]. BO MBC patients had a better adjusted OS compared with non-BO MBC [52.1 months (95% confidence interval (CI) 50.3-54.1) 34.7 months (95% CI 34.0-35.6) respectively]. The 5-year OS rate of BO MBC patients was 43.4% (95% CI 41.7-45.2). They also had a better PFS1 [13.1 months (95% CI 12.6-13.8) 8.5 months (95% CI 8.3-8.7), respectively]. This observation could be repeated in all subtypes. BO disease was an independent prognostic factor of OS [hazard ratio 0.68 (95% CI 0.65-0.72),  < 0.0001]. Results were concordant in all analyses.

Conclusion: BO MBC patients have better outcomes compared with non-BO MBC, consistently, through all MBC subtypes.
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http://dx.doi.org/10.1177/1758835920987657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841864PMC
January 2021

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site.

Br J Cancer 2021 02 16;124(4):777-785. Epub 2020 Nov 16.

Department of Genetics, Institut Curie, PSL Research University, 75005, Paris, France.

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs.

Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed.

Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011).

Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.
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http://dx.doi.org/10.1038/s41416-020-01153-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884736PMC
February 2021

Genetic markers and phosphoprotein forms of beta-catenin pβ-Cat552 and pβ-Cat675 are prognostic biomarkers of cervical cancer.

EBioMedicine 2020 Nov 20;61:103049. Epub 2020 Oct 20.

Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium (http://www.raids-fp7.eu/) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A "metagene" of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2].

Methods: To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA).

Findings: Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pβ-Cat552), ranked highest for good prognosis, while pβ-Cat675 was associated with worse prognosis.

Interpretation: These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pβ-Cat552 and pβ-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis.

Funding: European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer.
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http://dx.doi.org/10.1016/j.ebiom.2020.103049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581879PMC
November 2020

[Hot flushes and breast cancer with positive hormone receptors: Mechanisms and management].

Bull Cancer 2020 Nov 25;107(11):1171-1185. Epub 2020 Sep 25.

Institut Curie, département de chirurgie oncologique, Saint-Cloud, France; Institut Curie, Inserm U900, Saint-Cloud, France.

Breast cancer is the most frequently diagnosed cancer in women and the first cause of cancer death in France. Among the different subtypes of breast cancer, the predominant form is characterized by positive hormone receptors (more than 70% of breast cancers). Hormone therapy thus plays a key role in the strategy of management of these cancers both in adjuvant and metastatic situations. The two types of adjuvant hormone therapy used are selective estrogen receptor modulators and aromatase inhibitors. Fulvestrant, an anti-estrogen, is used alone or in combination with other molecules in metastatic situations. Hot flashes are one of the symptoms most frequently reported by patients under hormone therapy. Hormone replacement therapy, which is currently the most effective treatment for hot flashes, is contraindicated in patients with a personal history of breast cancer. Various therapeutic classes of drugs have been tested in this indication but without real efficacy in the various studies carried out to date, and moreover associated with non-negligible side effects. The recent discovery of the implication of the kisspeptin system located at the hypothalamic level in the mechanism of genesis of hot flashes opens the way to possible new symptomatic treatments for hot flashes. Neurokinin 3 receptor antagonists have shown encouraging preliminary results in postmenopausal cancer-free patients and could be considered in patients in hormonal therapy for breast cancer. Broader additional studies are needed to confirm these initial results.
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http://dx.doi.org/10.1016/j.bulcan.2020.07.005DOI Listing
November 2020

[Anxiety and depressive disorders in patients during the Covid-19 pandemic].

Bull Cancer 2020 Oct 11;107(10):1079-1080. Epub 2020 Sep 11.

Institut Curie, département de chirurgie, , 35, rue Dailly, 92210 Saint-Cloud, France; U900, équipe « Méthodes Statistiques pour la médecine personnalisée », Saint-Cloud, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486040PMC
October 2020

[Physical activity after breast cancer diagnosis and survival: A systematic review].

Bull Cancer 2020 Oct 22;107(10):1042-1055. Epub 2020 Sep 22.

Institut Curie, 35, rue Dailly, 92210 Saint-Cloud, France; Université de Versailles SQY, université Paris Saclay, UFR des sciences de la santé Simone-Veil, Paris, France; Institut Curie, Inserm U900, Saint-Cloud, France. Electronic address:

Introduction: The benefits of physical activity (PA) in breast cancer are currently recognized in primary prevention. The World Cancer Research Fund (WCRF) and then the National Cancer Institute (INCa) have reported conflicting results regarding the impact of post-diagnosis PA on breast cancer outcomes. The aim of this systematic review is to assess the association between PA after breast cancer diagnosis and overall mortality, specific mortality and risk of breast cancer recurrence in the literature.

Methods: Randomized trials, prospective cohorts and meta-analyses studying post-diagnosis PA and overall mortality, breast cancer mortality or risk of recurrence after breast cancer published between January 1, 2014 and October 1, 2019 were included. The articles selected by the INCa report prior to 2014 were included in the literature review.

Results: Eighteen articles have been selected. Studies unanimously concluded that overall mortality was reduced by post-diagnosis PA practice. For specific mortality, 5 meta-analyses showed a significant decrease in breast cancer mortality and 2 found a decrease in the risk of recurrence.

Conclusion: Post-diagnosis PA reduces overall mortality and appears to impact specific breast cancer mortality and risk of recurrence. However, these results need to be confirmed by larger randomized trials.
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http://dx.doi.org/10.1016/j.bulcan.2020.06.013DOI Listing
October 2020

Absenteeism and indirect costs during the year following the diagnosis of an operable breast cancer: A prospective multicentric cohort study.

J Gynecol Obstet Hum Reprod 2021 Jun 13;50(6):101871. Epub 2020 Jul 13.

Curie Institute, Surgical Oncology Department, Saint-Cloud, France.

Background: Diseases consequence on individual work as much as consequences of being absent from work are matters of interest for decision makers.

Methods: We analyzed lengths of absenteeism and related indirect costs for patients with a paid activity in the year following the diagnosis of early stage breast cancer, in the prospective OPTISOINS01 cohort. Both human capital and friction costs approach were considered for the valuation of lost working days (LWD). For the analysis, the friction period was estimated from recent French data. The statistical analysis included simple and multiple linear regression to search for the determinants of absenteeism and indirect costs.

Results: 93 % of the patients had at least one period of sick leave, with on average 2 period and 186 days of sick leave. 24 % of the patients had a part-time resumption after their sick leave periods, during 114 days on average (i.e. 41 LWD). Estimated indirect costs were 22,722.00 € and 7,724.00 € per patient, respectively for the human capital and the friction cost approach. In the multiple linear regression model, factors associated with absenteeism were: the invasive nature of the tumor (p = .043), a mastectomy (p = .038), a surgery revision (p = .002), a chemotherapy (p = .027), being a manager (p = .025) or a craftsman (p = .005).

Conclusion: Breast cancer lead to important lengths of absenteeism in the year following the diagnosis, but almost all patients were able to return to work. Using the friction cost or the human capital approach in the analysis led to an important gap in the results, highlighting the importance of considering both for such studies.
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http://dx.doi.org/10.1016/j.jogoh.2020.101871DOI Listing
June 2021

A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer.

Breast Cancer Res 2020 07 14;22(1):76. Epub 2020 Jul 14.

Stress and Cancer Laboratory, Equipe labelisée Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, F-75005, Paris, France.

Background: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients.

Methods: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5-2 cm without lymph node metastasis) with metastatic recurrence ("cases") and corresponding "controls" (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF).

Results: We found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that "cases" are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4 T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients.

Conclusions: This study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.
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http://dx.doi.org/10.1186/s13058-020-01311-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362513PMC
July 2020

[Impact of the COVID-19 epidemic on requests for initial care for breast cancer].

Bull Cancer 2020 Jun 30;107(6):620-622. Epub 2020 Apr 30.

Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France; Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France.

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http://dx.doi.org/10.1016/j.bulcan.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190490PMC
June 2020

Clinical Interest of Combining Transcriptomic and Genomic Signatures in High-Grade Serous Ovarian Cancer.

Front Genet 2020 17;11:219. Epub 2020 Mar 17.

Institut Curie, Stress and Cancer Laboratory, Equipe labelisée Ligue Nationale Contre le Cancer, PSL University, Paris, France.

High-grade serous ovarian cancer is one of the deadliest gynecological malignancies and remains a clinical challenge. There is a critical need to effectively define patient stratification in a clinical setting. In this study, we address this question and determine the optimal number of molecular subgroups for ovarian cancer patients. By studying several independent patient cohorts, we observed that classifying high-grade serous ovarian tumors into four molecular subgroups using a transcriptomic-based approach did not reproducibly predict patient survival. In contrast, classifying these tumors into only two molecular subgroups, fibrosis and non-fibrosis, could reliably inform on patient survival. In addition, we found complementarity between transcriptomic data and the genomic signature for homologous recombination deficiency (HRD) that helped in defining prognosis of ovarian cancer patients. We also established that the transcriptomic and genomic signatures underlined independent biological processes and defined four different risk populations. Thus, combining genomic and transcriptomic information appears as the most appropriate stratification method to reliably subgroup high-grade serous ovarian cancer patients. This method can easily be transferred into the clinical setting.
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http://dx.doi.org/10.3389/fgene.2020.00219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089941PMC
March 2020

[Carbon footprint and cancer: Time for green oncology?]

Bull Cancer 2020 May 31;107(5):612-613. Epub 2020 Mar 31.

Institut Curie, 35 rue Dailly, 92210 Saint-Cloud, France; UFR des Sciences de la santé Simone Veil (Université de Versailles SQY), Université Paris Saclay, Versailles France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.02.009DOI Listing
May 2020

A Pre-operative Score to Discriminate Fibroepithelial Lesions of the Breast: Phyllode Tumor or Fibroadenoma?

Anticancer Res 2020 Feb;40(2):1095-1100

Department of Surgical Oncology, Rene Huguenin, Saint-Cloud, France.

Background/aim: Fibroepithelial lesions (FEL) of the breast include fibroadenomas and phyllodes tumors (PT). Their histologic characteristics on core needle biopsy can overlap, while their clinical management is different. The aim of this study was to develop and to validate a pre-operative score for the diagnosis of PT with surgical decision rules.

Patients And Methods: We developed a pre-operative score for the diagnosis of PT by performing logistic regression on 217 FEL of the Rene Huguenin Hospital. This score and the surgical decision rules were validated on 87 FEL of the Lariboisiere Hospital.

Results: Three variables were independently and significantly associated with PT: age ≥40 years, mammography's tumor size ≥3 cm and PT diagnosed by CNB. The pre-operative score was based on these three criteria with values ranging from 0 to 10. Surgical decision rules were created: the low-risk group of PT (score≤2) had a sensitivity of 92.6% and a LR- of 0.2, the high-risk group (score>7) had a specificity of 93.5% and a LR+ of 4.4. In the validation sample, surgical decision rules were applied.

Conclusion: These surgical decision rules may prove useful in deciding which FEL needs surgical resection.
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http://dx.doi.org/10.21873/anticanres.14048DOI Listing
February 2020

[Desire for pregnancy and breast cancer].

Bull Cancer 2019 Dec;106(12S1):S53-S59

Département d'oncologie chirurgicale, hôpital René-Huguenin, Institut Curie, 35, rue Dailly, 92210 Saint-Cloud, France; Université Versailles-Saint-Quentin-en-Yvelines, 78180 Montigny-le-Bretonneux, France. Electronic address:

Breast cancer affects about 3,000 new women of childbearing age each year. The desire for pregnancy is therefore a frequent issue in the management of breast cancer. We reviewed the current state of knowledge and recommendations in high-risk women, on the consideration of this desire for pregnancy in therapeutic management, the way to approach it, the preservation of fertility in the care process and finally on the outcomes of pregnancy after breast cancer. We evaluated the desire for pregnancy, qualitatively and quantitatively, after breast cancer through a literature review.
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http://dx.doi.org/10.1016/S0007-4551(20)30048-5DOI Listing
December 2019

Associated Lichen Sclerosis Increases the Risk of Lymph Node Metastases of Vulvar Cancer.

J Clin Med 2020 Jan 17;9(1). Epub 2020 Jan 17.

Faculté de médecine de Créteil UPEC-Paris XII. Service de Gynécologie-Obstétrique et Médecine de la Reproduction. Centre Hospitalier Intercommunal de Créteil. 40 Avenue de Verdun, 94000 Créteil, France.

The most important prognostic factor in vulvar cancer is inguinal lymph node status at the time of diagnosis, even in locally advanced vulvar tumors. The aim of our study was to identify the risk factors of lymph node involvement in these women, especially the impact of lichen sclerosis (LS). We conducted a retrospective population-based cross-sectional study in two French referral gynecologic oncology institutions. We included all women diagnosed with a primary invasive vulvar cancer. Epithelial alteration adjacent to the invasive carcinoma was found in 96.8% ( = 395). The most frequently associated was LS in 27.7% ( = 113). In univariate analysis, LS ( = 0.009); usual type VIN ( = 0.04); tumor size >2 cm and/or local extension to vagina, urethra or anus ( < 0.01), positive margins ( < 0.01), thickness ( < 0.01) and lymphovascular space invasion (LVSI) ( < 0.01) were significantly associated with lymph node involvement. In multivariate analysis, only LS (OR 2.3, 95% CI [1.2-4.3]) and LVSI (OR 5.6, 95% CI [1.7-18.6]) remained significantly associated with positive lymph node. LS was significantly associated with older patients ( = 0.005), anterior localization ( = 0.017) and local extension (tumor size > 2 cm: = 0.001). LS surrounding vulvar cancer is an independent factor of lymph node involvement, with local extension and LVSI.
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http://dx.doi.org/10.3390/jcm9010250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019519PMC
January 2020

Mechanistic Signatures of Human Papillomavirus Insertions in Anal Squamous Cell Carcinomas.

Cancers (Basel) 2019 Nov 22;11(12). Epub 2019 Nov 22.

Institut Curie, Medical Oncology Department, Versailles Saint-Quentin University, 35 rue Dailly, 92210 Saint-Cloud, France.

The role of human papillomavirus (HPV) in anal squamous cell carcinoma (ASCC) carcinogenesis has been clearly established, involving the expression of viral oncoproteins and optional viral DNA integration into the host genome. In this article, we describe the various mechanisms and sites of HPV DNA insertion and assess their prognostic and predictive value in a large series of patients with HPV-positive ASCC with long-term follow-up. We retrospectively analyzed 96 tumor samples from 93 HPV-positive ASCC patients using the Capture-HPV method followed by Next-Generation Sequencing, allowing determination of HPV genotype and identification of the mechanisms and sites of viral genome integration. We identified five different mechanistic signatures of HPV insertions. The distribution of HPV signatures differed from that previously described in HPV-positive cervical carcinoma ( < 0.001). In ASCC samples, the HPV genome more frequently remained in episomal form (45.2%). The most common signature of HPV insertion was MJ-SC (26.9%), i.e., HPV-chromosomal junctions scattered at different loci. Functionally, HPV integration signatures were not associated with survival or response to treatment, but were associated with viral load ( = 0.022) and mutation ( = 0.0069). High viral load was associated with longer survival in both univariate ( = 0.044) and multivariate ( = 0.011) analyses. Finally, HPV integration occurred on most human chromosomes, but intragenic integration into the gene was recurrently observed ( = 4/51 tumors). Overall, the distribution of mechanistic signatures of HPV insertions in ASCC was different from that observed in cervical carcinoma and was associated with viral load and mutation. We confirmed recurrent targeting of by HPV integration, suggesting a role for this gene in ASCC carcinogenesis.
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http://dx.doi.org/10.3390/cancers11121846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966520PMC
November 2019

[Impact of nutrition on breast cancer mortality and risk of recurrence, a review of the evidence].

Bull Cancer 2020 Jan 26;107(1):61-71. Epub 2019 Sep 26.

Institut Curie, PSL Research University, département d'oncologie chirurgicale, 35, rue Dailly, 92210 Saint-Cloud, France. Electronic address:

Introduction: There is a growing interest in diets and their effects on cancer prognosis. In 2014, a report from the World Cancer Research Fund on diet and women with a history of breast cancer did not demonstrate a major effect on breast cancer prognosis. The aim of this literature review was to provide an update of knowledge in this area.

Methods: Randomized trials, prospective cohorts and meta-analyses published between 2012 and 2018 examining the impact of diet on recurrence risk and/or mortality after breast cancer were included, to achieve the objective. We evaluated study quality (according to Haute Autorité de Santé criteria) and the studied diets were categorized: macronutrients, micronutrients and selective foods.

Results: We selected eighteen articles that met levels of evidence 1 to 3. For macronutrients, a low-fat diet was associated with better survival. With regard to micronutrients, a diet rich in phytœstrogen reduced the risk of cancer recurrence. Finally, the adoption of a healthy diet was not associated with an improved prognosis for breast cancer but with an improvement in overall survival and risk of death from cardiovascular disease.

Discussion: This review suggests that nutrition influences the prognosis of breast cancer. Nevertheless, the level of evidence of the results was insufficient to make recommendations. Ultimately, a healthy and balanced diet could be encouraged in order to reduce global mortality.
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http://dx.doi.org/10.1016/j.bulcan.2019.08.009DOI Listing
January 2020

Direct medical and non-medical costs of a one-year care pathway for early operable breast cancer: Results of a French multicenter prospective study.

PLoS One 2019 10;14(7):e0210917. Epub 2019 Jul 10.

Health Economics Department, Institut Curie, Paris, France/CEMKA-EVAL, Bourg-La-Reine, France.

Introduction: The organization of health care for breast cancer (BC) constitutes a public health challenge to ensure quality of care, while also controlling expenditure. Few studies have assessed the global care pathway of early BC patients, including a description of direct medical costs and their determinants. The aims of this multicenter prospective study were to describe care pathways of BC patients in a geographic territory and to calculate the global direct costs of early stage BC during the first year following diagnosis.

Methods: OPTISOINS01 was a multicenter, prospective, observational study including early BC patients from diagnosis to one-year follow-up. Direct medical costs (in-hospital and out-of-hospital costs, supportive care costs) and direct non-medical costs (transportation and sick leave costs) were calculated by using a cost-of-illness analysis based on a bottom-up approach. Resources consumed were recorded in situ for each patient, using a prospective direct observation method.

Results: Data from 604 patients were analyzed. Median direct medical costs of 1 year of management after diagnosis in operable BC patients were €12,250. Factors independently associated with higher direct medical costs were: diagnosis on the basis of clinical signs, invasive cancer, lymph node involvement and conventional hospitalization for surgery. Median sick leave costs were €8,841 per patient and per year. Chemotherapy was an independent determinant of sick leave costs (€3,687/patient/year without chemotherapy versus €10,706 with chemotherapy). Forty percent (n = 242) of patients declared additional personal expenditure of €614/patient/year. No drivers of these costs were identified.

Conclusion: Initial stage of disease and the treatments administered were the main drivers of direct medical costs. Direct non-medical costs essentially consisted of sick leave costs, accounting for one-half of direct medical costs for working patients. Out-of-pocket expenditure had a limited impact on the household.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210917PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619952PMC
February 2020
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