Discordance in Hormone Receptor Status Among Primary, Metastatic, and Second Primary Breast Cancers: Biological Difference or Misclassification?

Introduction. Discordance in hormone receptor status has been observed between two breast tumors of the same patients; however, the degree of heterogeneity is debatable with regard to whether it reflects true biological difference or the limited accuracy of receptor assays. Methods. A Bayesian misclassification correction method was applied to data on hormone receptor status of two primary breast cancers from the Surveillance, Epidemiology, and End Results database between 1990 and 2010 and to data on primary breast cancer and paired recurrent/metastatic disease assembled from a meta‐analysis of the literature published between 1979 and 2014. Results. The sensitivity and specificity of the estrogen receptor (ER) assay were estimated to be 0.971 and 0.920, respectively. After correcting for misclassification, the discordance in ER between two primary breast cancers was estimated to be 1.2% for synchronous ipsilateral pairs, 5.0% for synchronous contralateral pairs, 14.6% for metachronous ipsilateral pairs, and 25.0% for metachronous contralateral pairs. Technical misclassification accounted for 53%–83% of the ER discordance between synchronous primary cancers and 11%–25% of the ER discordance between metachronous cancers. The corrected discordance in ER between primary tumors and recurrent or metastatic lesions was 12.4%, and there were more positive‐to‐negative changes (10.1%) than negative‐to‐positive changes (2.3%). Similar patterns were observed for progesterone receptor (PR), although the overall discordance in PR was higher. Conclusion. A considerable proportion of discordance in hormone receptor status can be attributed to misclassification in receptor assessment, although the accuracy of receptor assays was excellent. Biopsy of recurrent tumors for receptor retesting should be conducted after considering feasibility, cost, and previous ER/PR status. 摘要 引言. 现已发现同一患者的两种乳腺肿瘤之间存在激素受体状态的不一致性；然而，这是否反映了真正的生物学差异或受体检测精确性不够高，就此而言，异质性程度仍无定论。 方法. 检索监测、流行病学以及最终结果数据库1990 ∼ 2010年数据，利用Bayesian错误分类校正方法分析两种原发性乳腺癌的激素受体状态，同时从1979 ∼ 2014年发表的meta分析文献中收集原发乳腺癌及其配对的复发/转移性疾病数据并进行分析。 结果. 雌激素受体（ER）检测的敏感性和特异性分别为0.971、0.920。对错误分类校正后，分析两种原发性乳腺癌在ER方面的不一致性，对于同时性同侧配对肿瘤估计为1.2%，对于同时性对侧配对肿瘤估计为5.0%，对于异时性同侧配对肿瘤估计为14.6%，对于异时性对侧配对肿瘤估计为25.0%。就同时性原发性癌而言，技术上的错误分类导致了53%∼83%的ER不一致性；就异时性癌而言，技术上的错误分类导致了11%∼25%的ER不一致性。原发性肿瘤和复发或转移性病灶之间ER不一致性在改正后为12.4%，阳性到阴性的改变率（10.1%）比阴性到阳性的改变率（2.3%）更多。类似的模式也见于孕激素受体（PR），不过总体上PR中的不一致性更高。 结论. 尽管受体检测的精确性非常高，激素受体状态的不一致性在很大程度上归于受体评估的分类错误。肿瘤复发病灶活检时，在衡量了可行性、费用以及既往ER/PR状态后