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Article ; Online: Clinical relevance of circulating ESR1 mutations during endocrine therapy for advanced hormone-dependent endometrial carcinoma.

Drouyer, Aurélien / Beaussire, Ludivine / Jorda, Pauline / Leheurteur, Marianne / Guillemet, Cécile / Berghian, Anca / Georgescu, Dragos / Di Fiore, Frédéric / Perdrix, Anne / Clatot, Florian

BMC cancer

2023 Volume 23, Issue 1, Page(s) 1061

Abstract: Objective: Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and ... ...

Abstract	Objective: Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and can be monitored using circulating tumor DNA (ctDNA). The aim of this study was to explore the incidence and clinical relevance of circulating ESR1 mutations in patients treated by AI or megestrol acetate (M) for advanced endometrial carcinoma. Methodology: This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR + endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AI or M. Analyses were performed before exposure and at progression/during endocrine therapy. Results: Twenty-two patients were included: 13 were treated with AI, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed. 68.1% of the patients had low-grade endometrial carcinoma and 54.5% had received chemotherapy in the metastatic setting. The median duration of treatment was 152 days (min 47 - max 629) with AI and 155 days (min 91-max 1297) with M. Under AI, there was no ESR1 mutation at baseline, and one Y537C mutation at progression with a variant allele frequency (VAF) of 0.14%. Under M, one patient had a Y537C (VAF 0.2%) at baseline that disappeared during treatment. Another patient had a Y537S mutation emergence at progression after 91 days of treatment (VAF 1.83%). There was no significant difference between the circulating DNA concentration before and after hormone therapy (p = 0.16). Conclusion: ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.
MeSH term(s)	Female ; Humans ; Breast Neoplasms/pathology ; Clinical Relevance ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/genetics ; Estrogen Receptor alpha/genetics ; Hormones/therapeutic use ; Mutation ; Retrospective Studies
Chemical Substances	Estrogen Receptor alpha ; Hormones ; ESR1 protein, human
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-023-11559-x
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Article ; Online: Adjustment of young women with breast cancer after chemotherapy: A mediation model of emotional competence via emotional distress.

Baudry, Anne-Sophie / Yakimova, Sonya / Congard, Anne / Untas, Aurélie / Guiu, Séverine / Lefeuvre-Plesse, Claudia / Loustalot, Catherine / Guillemet, Cécile / Segura-Djezzar, Carine / Savoye, Aude-Marie / Coussy, Florence / Frenel, Jean-Sébastien / Vanlemmens, Laurence / Christophe, Véronique

Psycho-oncology

2022 Volume 31, Issue 5, Page(s) 848–855

Abstract: Objective: Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women ( ...

Abstract	Objective: Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women (≤45 years) with breast cancer (YWBC) on their specific quality of life (i.e. subjective experience related to daily difficulties and perceived repercussions of the disease and treatments) related to chemotherapy, via anxiety and depression symptoms. Methods: Two hundred fifty YWBC from 24 French centers completed a self-reported questionnaire after diagnosis (T1) and after the chemotherapy phase (T2), comprising the Young Women Breast Cancer Inventory, the Profile of EC and the Hospital Anxiety and Depression Scale. The indirect effect of EC (T1) on subjective experience (T2) via anxiety and depression symptoms (T2) was tested using regressions and the Macro PROCESS. Results: Emotional competence predicted fewer anxiety and depression symptoms at T1 and T2, and a better subjective experience at T2 via fewer anxiety and depression symptoms. Depression symptoms appeared to be a stronger mediator than anxiety symptoms on four dimensions (Support from close relatives, feeling of couple cohesion, body image and sexuality, management of children and everyday life), whereas anxiety symptoms appeared to be a stronger mediator on two dimensions (negative affectivity and apprehension about the future, deterioration of relationships). Conclusions: These results support the importance of developing psycho-affective interventions to reinforce the EC of YWBC during chemotherapy in order to facilitate the cognitive and emotional processes necessary for a better adjustment and subjective experience.
MeSH term(s)	Anxiety/psychology ; Breast Neoplasms/psychology ; Child ; Depression/psychology ; Female ; Humans ; Psychological Distress ; Quality of Life/psychology
Language	English
Publishing date	2022-01-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1118536-3
ISSN	1099-1611 ; 1057-9249
ISSN (online)	1099-1611
ISSN	1057-9249
DOI	10.1002/pon.5876
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Zs.A 3550: Show issues

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Article ; Online: Pain in desmoid-type fibromatosis: Prevalence, determinants and prognosis value.

Penel, Nicolas / Bonvalot, Sylvie / Le Deley, Marie-Cécile / Italiano, Antoine / Tlemsani, Camille / Pannier, Diane / Leguillette, Clémence / Kurtz, Jean-Emmanuel / Toulmonde, Maud / Thery, Julien / Orbach, Daniel / Dubray-Longeras, Pascale / Verret, Benjamin / Bertucci, François / Guillemet, Cécile / Laroche, Lucie / Dufresne, Armelle / Blay, Jean-Yves / Le Cesne, Axel

International journal of cancer

2023 Volume 153, Issue 2, Page(s) 407–416

Abstract: The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active ... ...

Abstract	The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.
MeSH term(s)	Adult ; Humans ; Male ; Fibromatosis, Aggressive/complications ; Fibromatosis, Aggressive/epidemiology ; Pain/epidemiology ; Pain/etiology ; Prevalence ; Prognosis ; Quality of Life
Language	English
Publishing date	2023-03-25
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34493
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 576: Show issues

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Article ; Online: Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients.

Allouchery, Violette / Beaussire, Ludivine / Perdrix, Anne / Sefrioui, David / Augusto, Laetitia / Guillemet, Cécile / Sarafan-Vasseur, Nasrin / Di Fiore, Frédéric / Clatot, Florian

Breast cancer research : BCR

2018 Volume 20, Issue 1, Page(s) 40

Abstract: Background: Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early ... ...

Abstract	Background: Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. Methods: This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment. Results: A total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41-85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment. Conclusions: Circulating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aromatase Inhibitors/administration & dosage ; Aromatase Inhibitors/adverse effects ; Breast Neoplasms/blood ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Chemotherapy, Adjuvant/adverse effects ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Estrogen Receptor alpha/blood ; Estrogen Receptor alpha/genetics ; Female ; Humans ; Middle Aged ; Mutation ; Recurrence
Chemical Substances	Aromatase Inhibitors ; ESR1 protein, human ; Estrogen Receptor alpha
Language	English
Publishing date	2018-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-018-0968-0
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Zs.A 5494: Show issues

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Article: Real-World Data on Newly Diagnosed

Bini, Marta / Quesada, Stanislas / Meeus, Pierre / Rodrigues, Manuel / Leblanc, Eric / Floquet, Anne / Pautier, Patricia / Marchal, Frédéric / Provansal, Magali / Campion, Loïc / Causeret, Sylvain / Gourgou, Sophie / Ray-Coquard, Isabelle / Classe, Jean-Marc / Pomel, Christophe / De La Motte Rouge, Thibault / Barranger, Emmanuel / Savoye, Aude Marie / Guillemet, Cécile /

Gladieff, Laurence / Demarchi, Martin / Rouzier, Roman / Courtinard, C / Romeo, Clémence / Joly, Florence

Cancers

2022 Volume 14, Issue 16

Abstract: Background: In spite of the frequency and clinical impact of : Methods: Consecutive patients with : Results: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. : Conclusions: This ...

Abstract	Background: In spite of the frequency and clinical impact of Methods: Consecutive patients with Results: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. Conclusions: This study reports the largest French multicenter cohort of
Language	English
Publishing date	2022-08-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14164040
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Article ; Online: Optimal timing of interval debulking surgery for advanced epithelial ovarian cancer: A retrospective study from the ESME national cohort.

Gynecologic oncology

2022 Volume 167, Issue 1, Page(s) 11–21

Abstract: Objective: Interval debulking surgery is recommended after 3-4 cycles (standard IDS) of neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC) not able to received upfront complete debulking surgery. However, real world practices frequently ...

Abstract	Objective: Interval debulking surgery is recommended after 3-4 cycles (standard IDS) of neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC) not able to received upfront complete debulking surgery. However, real world practices frequently report performing IDS after ≥5 NAC cycles (delayed IDS). The aim of this work was to evaluate the impact on survival of the number of NACT cycles before IDS. Methods: We identified from a French national database, women with newly diagnosed EOC who underwent IDS from January 2011 to December 2016. Progression free survival (PFS) and overall survival (OS) were compared using Cox model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched-pair analysis. Results: 928 patients treated by IDS for which our propensity score could be applied were identified. After a median follow-up of 49.0 months (95% CI [46.0;52.9]); from the IPTW analysis, median PFS was 17.6 months and 11.5 months (HR = 1.42; CI 95% [1.22-1.67]; p < 0.0001); median OS was 51.2 months and 44.3 months (HR = 1.29; CI 95% [1.06-1.56]; p = 0.0095) for the standard and delayed IDS groups. From the matched-pair analysis (comparing 352 patients for each group), standard IDS was associated with better PFS (HR = 0,77; CI 95% [0.65-0.90]; p = 0.018) but not significantly associated with better OS (HR = 0,84; CI 95% [0.68-1,03]; p = 0.0947). Conclusions: Carrying IDS after ≥5 NACT cycles seems to have a negative effect on patients survival. The goal of IDS surgery is complete resection and should not be performed after >3-4 NACT cycles.
MeSH term(s)	Carcinoma, Ovarian Epithelial/drug therapy ; Carcinoma, Ovarian Epithelial/etiology ; Carcinoma, Ovarian Epithelial/surgery ; Chemotherapy, Adjuvant/adverse effects ; Cytoreduction Surgical Procedures ; Female ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/surgery ; Retrospective Studies
Language	English
Publishing date	2022-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2022.08.005
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Zs.A 885: Show issues

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Article ; Online: Lack of Prognostic Value of CTNNB1 Mutation Profile in Desmoid-Type Fibromatosis.

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 28, Issue 18, Page(s) 4105–4111

Abstract: Purpose: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations.: Experimental design: ALTITUDES (NCT02867033) was a nationwide prospective cohort ... ...

Abstract	Purpose: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations. Experimental design: ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, CTNNB1 molecular alterations were identified using next-generation sequencing or Sanger sequencing. The primary endpoint was event-free survival (EFS; progression, relapse, or death). We enrolled 628 patients managed by active surveillance, surgical resection, or systemic treatment as first-line therapy. Results: Overall, 516 (82.2%) patients [368 females (71.3%), median age 40.3 years (range, 1-89)] were eligible for analysis. In 435 (84.3%) cases, there was one CTNNB1 molecular alteration: p.T41A, p.S45F, or p.S45P. The first-line management was active surveillance in 352 (68.2%), surgical resection in 120 (23.3%), and systemic treatments in 44 (8.5%) patients. CTNNB1 mutation distribution was similar across the three therapeutic groups. The median follow-up period was 24.7 (range, 0.4-59.7) months. The estimated 3-year EFS rate was 66.2% [95% confidence interval (CI), 60.5%-71.2%]. DF harboring p.S45F was significantly associated with male sex (P = 0.03), non-abdominal wall sites (P = 0.05), pain (P = 0.007), and large tumor size (P = 0.025). CTNNB1 p.S45F mutation was not significantly associated with EFS, either in univariate (HR, 1.06; 95% CI, 0.65-1.73; P = 0.81) or in multivariate analysis (HR, 0.91; 95% CI, 0.55-1.49; P = 0.71). Conclusions: We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS. See related commentary by Greene and Van Tine, p. 3911.
MeSH term(s)	Adult ; Female ; Humans ; Male ; beta Catenin/genetics ; Cohort Studies ; Fibromatosis, Aggressive/diagnosis ; Fibromatosis, Aggressive/genetics ; Fibromatosis, Aggressive/pathology ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/mortality ; Prognosis ; Prospective Studies
Chemical Substances	beta Catenin ; CTNNB1 protein, human
Language	English
Publishing date	2022-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-4235
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Zs.A 4223: Show issues

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Article ; Online: Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial.

The Lancet. Oncology

2022 Volume 23, Issue 8, Page(s) 1044–1054

Abstract: Background: Metastatic leiomyosarcomas have a poor prognosis, and currently doxorubicin alone is used as the standard first-line treatment. Doxorubicin combined with trabectedin has shown promising results in phase 1 and 2 studies. We aimed to identify ... ...

Abstract	Background: Metastatic leiomyosarcomas have a poor prognosis, and currently doxorubicin alone is used as the standard first-line treatment. Doxorubicin combined with trabectedin has shown promising results in phase 1 and 2 studies. We aimed to identify and compare the progression-free survival of patients with metastatic or unresectable uterine or soft tissue leiomyosarcoma treated with doxorubicin and trabectedin combined as first-line therapy versus doxorubicin alone in a phase 3 trial. Methods: LMS-04 was a randomised, multicentre, open-label, superiority phase 3 trial, which included patients from 20 centres of the French Sarcoma Group (anticancer centers or hospitals with an oncological unit) in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-1, and had metastatic or relapsed unresectable leiomyosarcomas that had not previously been treated with chemotherapy. Patients were randomly assigned (1:1), by means of an interactive web response system (permuted blocks of different sizes from two to six), to receive either intravenous doxorubicin alone (75 mg/m Findings: Between Jan 18, 2017, and March 21, 2019, 150 patients were enrolled (67 with uterine leiomyosarcomas and 83 with soft tissue leiomyosarcomas) and included in the intention-to-treat population: 76 in the doxorubicin alone group and 74 in the doxorubicin plus trabectedin group. The median duration of follow-up was 36·9 months (IQR 30·0-43·2) in the doxorubicine group and 38·8 months (32·7-44·2) in the doxorubicin plus trabectedin group. Median progression-free survival was significantly longer with doxorubicin plus trabectedin versus doxorubicin alone (12·2 months [95% CI 10·1-15·6] vs 6·2 months [4·1-7·1]; adjusted hazard ratio 0·41 [95% CI 0·29-0·58]; p<0·0001). The most common grade 3-4 adverse events were neutropenia (ten [13%] of 75 patients in the doxorubicin alone group vs 59 [80%] in the doxorubicin plus trabectedin group), anaemia (four [5%] vs 23 [31%]), thrombocytopenia (0 vs 35 [47%]), and febrile neutropenia (seven [9%] vs 21 [28%]). Nine (12%) patients in the doxorubicin alone group and 15 (201%) patients in the doxorubicin plus trabectedin group has serious adverse events. There was only one treatment-related death, reported in the doxorubicin alone group (cardiac failure). Interpretation: Doxorubicin plus trabectedin in first-line therapy was found to significantly increase progression-free survival in patients with metastatic or unresectable leiomyosarcomas compared with doxorubicin alone, despite a higher but manageable toxicity, and could be considered an option for the first-line treatment of metastatic leiomyosarcomas. Funding: PharmaMar.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Disease-Free Survival ; Doxorubicin ; Female ; Humans ; Leiomyosarcoma/drug therapy ; Trabectedin
Chemical Substances	Doxorubicin (80168379AG) ; Trabectedin (ID0YZQ2TCP)
Language	English
Publishing date	2022-07-11
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(22)00380-1
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer.

Clatot, Florian / Perdrix, Anne / Beaussire, Ludivine / Lequesne, Justine / Lévy, Christelle / Emile, George / Bubenheim, Michael / Lacaille, Sigrid / Calbrix, Céline / Augusto, Laetitia / Guillemet, Cécile / Alexandru, Cristina / Fontanilles, Maxime / Sefrioui, David / Burel, Lucie / Guénot, Sabine / Richard, Doriane / Sarafan-Vasseur, Nasrin / Di Fiore, Frédéric

Breast cancer research : BCR

2020 Volume 22, Issue 1, Page(s) 56

Abstract: Background: Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively ... ...

Abstract	Background: Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI). Methods: Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC. Results: Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0-8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression. Conclusion: The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting. Trial registration: ClinicalTrials.gov, NCT02473120. Registered 16 June 2015-retrospectively registered after one inclusion (first inclusion 1 June 2015).
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aromatase Inhibitors/therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Cohort Studies ; Disease Progression ; Drug Resistance, Neoplasm ; Estrogen Receptor alpha/blood ; Estrogen Receptor alpha/genetics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Mucin-1/blood ; Mutation ; Neoplasm Metastasis ; Prognosis ; Prospective Studies ; Survival Rate
Chemical Substances	Aromatase Inhibitors ; Biomarkers, Tumor ; Circulating Tumor DNA ; ESR1 protein, human ; Estrogen Receptor alpha ; Mucin-1
Language	English
Publishing date	2020-05-28
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-020-01290-x
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Article ; Online: Clinicopathological characterization of a real-world multicenter cohort of endometrioid ovarian carcinoma: Analysis of the French national ESME-Unicancer database.

De Nonneville, Alexandre / Zemmour, Christophe / Frank, Sophie / Joly, Florence / Ray-Coquard, Isabelle / Costaz, Hèlène / Classe, Jean-Marc / Floquet, Anne / De la Motte Rouge, Thibault / Colombo, Pierre-Emmanuel / Sauterey, Baptiste / Leblanc, Eric / Pomel, Christophe / Marchal, Frédéric / Barranger, Emmanuel / Savoye, Aude-Marie / Guillemet, Cécile / Petit, Thierry / Pautier, Patricia /

Rouzier, Roman / Gladieff, Laurence / Simon, Gaëtane / Courtinard, Coralie / Sabatier, Renaud

Gynecologic oncology

2021 Volume 163, Issue 1, Page(s) 64–71

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Carcinoma, Endometrioid/genetics ; Carcinoma, Endometrioid/mortality ; Carcinoma, Endometrioid/pathology ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/mortality ; Carcinoma, Ovarian Epithelial/pathology ; Databases, Factual ; Female ; Humans ; Middle Aged ; Mutation ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Retrospective Studies ; Young Adult
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.07.019
Database	MEDical Literature Analysis and Retrieval System OnLINE

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