BCRP/ABCG2 蛋白在浸润性乳腺癌中的表达及其对新辅助化疗的反应。
Expression of BCRP/ABCG2 Protein in Invasive Breast Cancer and Response to Neoadjuvant Chemotherapy.
机构信息
Breast Cancer Center, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China,
Breast Cancer Center, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
出版信息
Oncol Res Treat. 2022;45(3):94-101. doi: 10.1159/000520871. Epub 2021 Nov 12.
BACKGROUND
Breast cancer resistance protein (BCRP), or ATP-binding cassette subfamily G member 2 (ABCG2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma.
OBJECTIVES
The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy.
METHODS
In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated.
RESULTS
The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (luminal B, 80%; luminal A, 78%), compared with other molecular subtypes (triple-negative, 63%; HER2+, 58%, p = 0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (p = 0.001) and tumor size (p = 0.011) demonstrated a statistically significant correlation. Low BCRP/ABCG2 expression was associated with an increased pathological complete response (pCR) rate of 38%, higher than the 19% in tumors with high BCRP/ABCG2 expression (p = 0.002). In multivariable analysis, BCRP/ABCG2 and hormone receptor (HR) expression were identified as independent risk factors of pCR (p = 0.003 and p = 0.013, respectively).
CONCLUSIONS
BCRP/ABCG2 is highly expressed in HR-positive breast cancer. High BCRP/ABCG2 expression is associated with lymphatic metastasis, tumor size, and poor pCR. BCRP/ABCG2 may be a novel potential biomarker that can predict clinical progression and therapy response after neoadjuvant chemotherapy.
背景
乳腺癌耐药蛋白（BCRP），也称为 ATP 结合盒亚家族 G 成员 2（ABCG2），是一种 ATP 结合盒（ABC）转运蛋白，介导底物药物从细胞内的能量依赖性转运。其过度表达可能导致体外固有耐药性。然而，目前的文献尚未阐明 BCRP/ABCG2 在浸润性乳腺癌中的临床意义。
目的
本研究旨在验证 BCRP/ABCG2 在浸润性乳腺癌中的表达及其在新辅助化疗反应中的作用。
方法
本研究对 222 例患者进行了术前核心活检。采用免疫组织化学法检测癌组织中 BCRP/ABCG2 的表达。研究了 BCRP/ABCG2 表达与临床病理特征、分子亚型以及新辅助化疗后治疗反应的相关性。
结果
结果显示，BCRP/ABCG2 在不同的分子亚型中表达。高 BCRP/ABCG2 表达的患者比例在 luminal A 和 luminal B 肿瘤中相似（luminal B，80%；luminal A，78%），与其他分子亚型相比（三阴性，63%；HER2+，58%，p=0.05）。BCRP/ABCG2 表达与淋巴结转移数（p=0.001）和肿瘤大小（p=0.011）呈显著相关。低 BCRP/ABCG2 表达与较高的病理完全缓解（pCR）率 38%相关，高于高 BCRP/ABCG2 表达的肿瘤的 19%（p=0.002）。多变量分析显示，BCRP/ABCG2 和激素受体（HR）表达是 pCR 的独立危险因素（p=0.003 和 p=0.013）。
结论
BCRP/ABCG2 在 HR 阳性乳腺癌中高表达。高 BCRP/ABCG2 表达与淋巴结转移、肿瘤大小和较差的 pCR 相关。BCRP/ABCG2 可能是一种新的潜在生物标志物，可预测新辅助化疗后的临床进展和治疗反应。
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