Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer

被引：23

作者：

Bidard, F. -C. ^{[1
,2
]}

Ng, C. K. Y. ^{[2
]}

Cottu, P. ^{[1
]}

Piscuoglio, S. ^{[2
]}

Escalup, L. ^{[3
]}

Sakr, R. A. ^{[4
]}

Reyal, F. ^{[5
]}

Mariani, P. ^{[5
]}

Lim, R. ^{[2
]}

Wang, L. ^{[2
]}

Norton, L. ^{[6
]}

Servois, V. ^{[7
]}

Sigal, B. ^{[8
]}

Vincent-Salomon, A. ^{[8
]}

Weigelt, B. ^{[2
]}

Pierga, J. -Y. ^{[1
,9
]}

Reis-Filho, J. S. ^{[2
,10
,11
]}

机构：

[1] Inst Curie, Dept Med Oncol, F-75005 Paris, France

[2] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA

[3] Inst Curie, Dept Pharm, F-75005 Paris, France

[4] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA

[5] Inst Curie, Dept Surg, F-75005 Paris, France

[6] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

[7] Inst Curie, Dept Radiol, F-75005 Paris, France

[8] Inst Curie, Dept Pathol, F-75005 Paris, France

[9] Paris Descartes Univ, Paris, France

[10] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10021 USA

来源：

ANNALS OF ONCOLOGY | 2015年 / 26卷 / 08期

关键词：

precision medicine; breast cancer; HER3; mutations; dual HER2 blockade; massively parallel sequencing; MUTATIONS; CARCINOMAS; AMPLICON;

D O I：

10.1093/annonc/mdv217

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2. Patients and methods: Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation. Results: HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis. Discussion: This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.

引用

页码：1704 / 1709

页数：7

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