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

被引：30

作者：

Clatot, Florian ^{[1
,2
]}

Perdrix, Anne ^{[2
,3
]}

Beaussire, Ludivine ^{[2
]}

Lequesne, Justine ^{[4
]}

Levy, Christelle ^{[5
]}

Emile, George ^{[5
]}

Bubenheim, Michael ^{[6
]}

Lacaille, Sigrid ^{[2
]}

Calbrix, Celine ^{[3
]}

Augusto, Laetitia ^{[1
]}

Guillemet, Cecile ^{[1
]}

Alexandru, Cristina ^{[1
]}

Fontanilles, Maxime ^{[1
,2
]}

Sefrioui, David ^{[2
]}

Burel, Lucie ^{[4
]}

Guenot, Sabine ^{[4
]}

Richard, Doriane ^{[4
]}

Sarafan-Vasseur, Nasrin ^{[2
]}

Di Fiore, Frederic ^{[1
,2
]}

机构：

[1] Ctr Henri Becquerel, Dept Med Oncol, Rouen, France

[2] Normandie Univ, Rouen Univ Hosp, Normandy Ctr Genom & Personalized Med, IRON Grp,UNIROUEN,INSERM,U1245, Rouen, France

[3] Ctr Henri Becquerel, Dept Biopathol, Rouen, France

[4] Ctr Henri Becquerel, Clin Res Unit, Rouen, France

[5] Ctr Francois Baclesse, Inst Normand Sein, Caen, France

[6] Rouen Univ Hosp, Dept Clin Res & Innovat, Rouen, France

来源：

BREAST CANCER RESEARCH | 2020年 / 22卷 / 01期

关键词：

ESR1; mutation; Breast cancer; Circulating DNA; CA-15.3; Cell-free DNA; Aromatase inhibitor; CELL-FREE DNA; TUMOR DNA; CEA; OUTCOMES; MARKERS;

D O I：

10.1186/s13058-020-01290-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：12

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