转移性乳腺癌患者中曲妥珠单抗疗效与 Her2/EGFR-PDGFR 通路异常的关系。

Her2/EGFR-PDGFR pathway aberrations associated with tamoxifen response in metastatic breast cancer patients.

机构信息

Medical Oncology Department, National Cancer Institute (NCI), Cairo University, Cairo, 11976, Egypt.

Medical Biochemistry and molecular biology, Cancer Biology Department, NCI, Cairo University, Cairo, 11976, Egypt.

出版信息

J Egypt Natl Canc Inst. 2022 Jul 25;34(1):31. doi: 10.1186/s43046-022-00132-5.

DOI:10.1186/s43046-022-00132-5

PMID:35871690

Abstract

BACKGROUND

Metastatic breast cancer (MBC) is a major health problem worldwide. Some patients improve on tamoxifen and others do not respond to treatment. Therefore, the aim of the current study is to assess genetic aberrations in the Her2/EGFR-PDGFR pathway associated with tamoxifen response in MBC patients.

METHODS

This is a retrospective cohort study, including 157 hormone receptors positive, locally recurrent inoperable and/or MBC patients on tamoxifen treatment. Patients were categorized into 78 (49.7%) tamoxifen responders and 79 (50.3%) tamoxifen non-responder patients. Genetic aberrations of 84 genes involved in the Her2/EGFR-PDGFR pathway were assessed in the tumor tissue samples obtained from the patients using SA-Bioscience assay. The identified panel was correlated to patients' response to treatment, to detect the differentially expressed genes in tamoxifen responders and non-responders.

RESULTS

One hundred twenty-three (78.3%) patients were estrogen receptor (ER) and progesterone receptor (PR) positive, 108 (68.8%) were ER only positive, and 78 (49.7%) were PR only positive. There were 56 genes overexpressed in the refractory group compared to responders. However, only five out of these 56 genes, Janus kinase 1 (JAK1), collagen type I alpha 1 (COL1A1), GRB2-associated binding protein 1 (GAB1), fibronectin-1 (FN1), and MAP kinase-interacting serine/threonine-protein kinase (MKNK1), showed statistical significance between the two groups. Patients with bone metastasis showed a better response to treatment compared to those with metastatic deposits in other sites such as visceral metastasis (P < 0.005).

CONCLUSIONS

Genetic profiling using simple quantitative real-time polymerase chain reaction (qRT-PCR) protocols could be used to assess response to tamoxifen treatment in MBC patients. According to our data, a five-gene panel in the EGFR pathway (JAK1, COL1A1, GAB1, FN1 and MKNK1) could be used to categorize MBC patients into groups according to treatment response.

摘要

背景

转移性乳腺癌（MBC）是全球范围内的一个主要健康问题。一些患者在接受他莫昔芬治疗后病情改善，而另一些患者则对治疗无反应。因此，本研究旨在评估与 MBC 患者他莫昔芬治疗反应相关的 Her2/EGFR-PDGFR 通路中的遗传异常。

方法

这是一项回顾性队列研究，纳入了 157 例接受他莫昔芬治疗的激素受体阳性、局部复发不可切除和/或转移性乳腺癌患者。患者分为 78 例（49.7%）他莫昔芬应答者和 79 例（50.3%）他莫昔芬无应答者。使用 SA-Bioscience 检测法评估来自患者的肿瘤组织样本中涉及 Her2/EGFR-PDGFR 通路的 84 个基因的遗传异常。鉴定的面板与患者对治疗的反应相关，以检测他莫昔芬应答者和无应答者中差异表达的基因。

结果

123 例（78.3%）患者雌激素受体（ER）和孕激素受体（PR）阳性，108 例（68.8%）仅 ER 阳性，78 例（49.7%）仅 PR 阳性。在耐药组中有 56 个基因过表达与应答者相比。然而，在这 56 个基因中，只有 5 个基因，即 Janus 激酶 1（JAK1）、Ⅰ型胶原α1 链（COL1A1）、GRB2 相关结合蛋白 1（GAB1）、纤维连接蛋白 1（FN1）和丝氨酸/苏氨酸蛋白激酶相互作用的丝裂原激活蛋白激酶（MKNK1），在两组之间具有统计学意义。骨转移患者的治疗反应优于其他部位转移（如内脏转移）的患者（P<0.005）。