Erdem Gokmen U, Altundag Kadri, Ozdemir Nuriye Y, Sahin Suleyman, Demirci Nebi S, Karatas Fatih, Bozkaya Yakup, Aytekin Aydin, Tasdemir Vildan, Aslan Alma C, Sever Ali R, Zengin Nurullah
Ankara Numune Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.
J BUON. 2017 Mar-Apr;22(2):365-376.
It is well-known that tumor phenotype may change during the progression of breast cancer (BC). The purpose in this study was to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary and recurrent/metastatic lesions (RML) and also to evaluate the prognostic significance of change in tumor phenotype on survival in patients with metastatic BC.
The medical records of 6638 patients with BC from two breast centers treated between 1992 and 2015 were retrospectively analyzed. Of the 6638 patients, 549 cases in whom recurrence was histologically proven by biopsy or by surgical resection were enrolled into this study.
Our presentation 13.5% of the patients had metastatic disease. Biopsy on recurrence was obtained from distant metastasis sites in 250 (63.6%) patients or from locoregional soft tissues/lymph-nodes in 143 (36.4%). Receptor discordance in ER, PgR and HER2 expressions between primary and RML were 27.2% (p=0.32), 38.6% (p<0.001) and 14.4% (p=0.007), respectively. Subsequent gain of ER and PgR showed significantly higher overall survival (OS) and post-recurrence survival (PRS) compared to the corresponding concordant-negative patients (119 vs 57 months, p=0.001 and 56 vs 31 months, p=0.03 for ER, 148 vs 58 months, p=0.003 and 64 vs 31 months, p=0.01 for PgR, respectively), hormone receptor (HR) loss was associated with worse OS. Similarly, HER2-loss cases experienced poorer PRS and OS outcomes, compared with those having stable HER2 expression (median 26 vs 60 months, p=0.009 for PRS and median 60 vs 111 months, p=0.06 for OS, respectively).
This study confirmed the receptor discordance in ER/PgR and HER2 receptor expressions between primary and RML in patients with metastatic BC. As the loss of receptor expression is the most responsible factor for the discordance, treatments of recurrent/metastatic tumors should be individualized on the basis of molecular and genomic properties.
众所周知，在乳腺癌（BC）进展过程中肿瘤表型可能会发生变化。本研究的目的是比较原发性和复发/转移性病灶（RML）之间雌激素受体（ER）、孕激素受体（PgR）和人表皮生长因子受体2（HER2）的不一致性，并评估肿瘤表型变化对转移性BC患者生存的预后意义。
回顾性分析了1992年至2015年间在两个乳腺中心接受治疗的6638例BC患者的病历。在这6638例患者中，549例经活检或手术切除组织学证实复发的患者纳入本研究。
我们的数据显示13.5%的患者有转移性疾病。250例（63.6%）患者复发时的活检取自远处转移部位，143例（36.4%）取自局部软组织/淋巴结。原发性和RML之间ER、PgR和HER2表达的受体不一致率分别为27.2%（p = 0.32）、38.6%（p < 0.001）和14.4%（p = 0.007）。与相应的一致性阴性患者相比，随后ER和PgR的获得显示出显著更高的总生存期（OS）和复发后生存期（PRS）（ER分别为119个月对57个月，p = 0.001和56个月对31个月，p = 0.03；PgR分别为148个月对58个月，p = 0.003和64个月对31个月，p = 0.01），激素受体（HR）丢失与较差的OS相关。同样，与HER2表达稳定的患者相比，HER2丢失的病例经历了更差的PRS和OS结局（PRS中位数为26个月对60个月，p = 0.009；OS中位数为60个月对111个月，p = 0.06）。
本研究证实了转移性BC患者原发性和RML之间ER/PgR和HER2受体表达的受体不一致性。由于受体表达的丢失是不一致性的最主要原因，复发/转移性肿瘤的治疗应基于分子和基因组特性进行个体化。
