HR阳性乳腺癌新辅助治疗后HER2阴性亚组蛋白水平表达的演变及与临床病理特征的相关性分析

Revaluation of protein expression levels in HER2-negative subgroups of hormone receptor-positive breast cancer after neoadjuvant therapy and its correlation with clinicopathological features

目的 探讨激素受体(hormone receptor, HR)阳性、HER2阴性亚组[极低表达(Ultra-low)和完全无表达(Null)]乳腺癌新辅助治疗前后的演变及其与临床病理特征的关系。方法 回顾性分析术前接受新辅助治疗且治疗后未达到病理完全缓解(pathological complete response, pCR)的连续性乳腺癌病例255例,采用免疫组化法检测ER、PR、HER2和Ki67的表达情况,并评价HER2阴性亚组表达水平新辅助治疗后的演变及与乳腺癌临床病理特征的关系。结果 255例乳腺癌患者中新辅助治疗前HER2-0和HER2-1+的例数分别为116例(45.5%)和139例(54.5%),HER2-0进一步划分为Null 61例(23.9%)和Ultra-low 55例(21.6%)。新辅助治疗后HER2-0和HER2-1+例数分别为117例(45.9%)和138例(54.1%),HER2-0进一步划分为Null 64例(25.1%)和Ultra-low 53例(20.8%)。新辅助治疗后有121例(47.5%)患者HER2表达水平发生了转变,其中,新辅助治疗前为HER2 Ultra-low,治疗后转变为1+,转变率最高,为11.76%(30/255),其次为1+转变为Ultra-low,转变率为10.98%(28/255);新辅助治疗后,HER2 Ultra-low组55例中44例发生了转变,其转变率高达80%。χ^(2)检验显示新辅助治疗前HER2表达与新辅助治疗后肿瘤最大径(≤2 cm,>2 cm)有关(χ^(2)=6.106,P=0.047),治疗前HER2 1+的患者治疗后肿瘤最大径≤2 cm居多;新辅助治疗后HER2表达与新辅助治疗后脉管瘤栓有关(χ^(2)=6.975,P=0.029),治疗后HER2 Ultra-low患者更容易出现脉管瘤栓。结论 HR阳性的乳腺癌中,对HER2-0重新划分为Ultra-low和Null后,新辅助治疗后HER2转变率明显增高,并且Ultra-low转变率最高,说明Ultra-low病例在新辅助治疗后具有高度不稳定性,对于新辅助治疗后残余病灶HER2的检测并区分Ultra-low的表达十分重要。

Purpose To explore the evolution of HER2 negative subgroups(IHC Null,Ultra-low and 1+)in breast cancer with hormone receptor(HR)positive before and after neoadjuvant therapy, and the relationship with clinical pathological features. Methods There were 255 patients who did not achieve pathological complete response (pCR) consecutively after neoadjuvant therapy. Immunohistochemistry was used to detect the expression of ER, PR, HER2 and Ki67 and to evaluate the evolution of HER2-negative subgroups after neoadjuvant therapy and its relationship with clinicopathological characteristics. Results Among the 255 patients included in this study, HER2 expression was 0 and 1+ in 116 cases (45.5%) and 139 cases (54.7%) respectively before neoadjuvant therapy, and then HER2 0 was further divided into Null group (61 cases, 23.9%) and Ultra-low group (55 cases, 21.6%). After neoadjuvant therapy, HER2 expression was 0 and 1+ in 117 cases (45.9%) and 138 cases (54.1%) respectively, and then HER2 0 was further divided into Null group(64 cases, 25.1%) and Ultra-low group (53 cases, 20.8%). HER2 status changed in 121 patients (47.5%) after neoadjuvant therapy. The highest conversion rate was from HER2 Ultra-low before neoadjuvant therapy to 1+ after neoadjuvant therapy, with a conversion rate of 11.76% (30/255), followed by HER2 1+ to the Ultra-low, with a conversion rate of 10.98% (28/255). After the neoadjuvant therapy, 44 of 55 cases had transformation in the HER2 Ultra-low group, with the conversion rate of as high as 80%. Chi-square test showed that HER2 expression before neoadjuvant therapy was correlated with the maximum tumor diameter (≤2 cm, > 2cm) after neoadjuvant therapy (χ^(2)=6.106, P =0.047);the tumor of HER2 1+ before neoadjuvant therapy was mostly 2 cm or less in the diameter. The HER2 status after neoadjuvant therapy was correlated with the tumor thrombus (χ^(2)=6.975, P =0.029). Patients with HER2 Ultra-low after treatment were more likely to have vascular invasion. Conclusion In HR positive breast cancer, when the HER2 0 cases are divided into Ultra-low and Null subgroups, the HER2 conversion rate increases significantly after neoadjuvant therapy, in which the Ultra-low conversion rate is the highest, indicating that the HER2 Ultra-low cases are highly unstable after neoadjuvant therapy. It is important to detect HER2 expression in residual lesions after neoadjuvant therapy and to identify the Ultra-low HER2 expression subgroup.