Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, the Netherlands.
J Natl Cancer Inst. 2018 Jun 1;110(6):568-580. doi: 10.1093/jnci/djx273.
In metastatic breast cancer, hormone and/or human epidermal growth factor receptor 2 (HER2)-targeted therapy decision-making is still largely based on tissue characteristics of the primary tumor. However, a change of estrogen receptor alpha (ERα), progesterone receptor (PR), and HER2 status in distant metastases has frequently been reported. The actual incidence of this phenomenon has been debated.
We performed a meta-analysis including 39 studies assessing receptor conversion from primary breast tumors to paired distant breast cancer metastases. We noted the direction of change (positive to negative or vice versa) and performed subgroup analyses for different thresholds for positivity, the type of test used to assess HER2 receptor status, and metastasis location-specific differences (two-sided tests).
Overall, the incidence of receptor conversion varied largely between studies. For ERα, PR, and HER2, we found that random effects pooled positive to negative conversion percentages of 22.5% (95% confidence interval [CI] = 16.4% to 30.0%), 49.4% (95% CI = 40.5% to 58.2%), and 21.3% (95% CI = 14.3% to 30.5%), respectively. Negative to positive conversion percentages were 21.5% (95% CI = 18.1% to 25.5%), 15.9% (95% CI = 11.3% to 22.0%), and 9.5% (95% CI = 7.4% to 12.1%). Furthermore, ERα discordance was statistically significantly higher in the central nervous system and bone compared with liver metastases (20.8%, 95% CI = 15.0% to 28.0%, and 29.3%, 95% CI = 13.0% to 53.5%, vs 14.3%, 95% CI = 11.3% to 18.1, P = .008 and P < .001, respectively), and PR discordance was higher in bone (42.7%, 95% CI = 35.1% to 50.6%, P < .001) and liver metastases (47.0%, 95% CI = 41.0% to 53.0%, P < .001) compared with central nervous system metastases (23.3%, 95% CI = 16.0% to 32.6%).
Receptor conversion for ERα, PR, and HER2 occurs frequently in the course of disease progression in breast cancer. Large prospective studies assessing the impact of receptor conversion on treatment efficacy and survival are needed. Meanwhile, reassessing receptor status in metastases is strongly encouraged.
在转移性乳腺癌中，激素和/或人表皮生长因子受体 2（HER2）靶向治疗的决策仍然主要基于原发性肿瘤的组织特征。然而，远处转移灶中雌激素受体α（ERα）、孕激素受体（PR）和 HER2 状态的改变经常被报道。这种现象的实际发生率存在争议。
我们进行了一项荟萃分析，纳入了 39 项评估原发性乳腺癌肿瘤与配对远处乳腺癌转移灶受体转换的研究。我们注意到变化的方向（阳性转为阴性或反之亦然），并针对不同的阳性阈值、用于评估 HER2 受体状态的检测类型以及转移灶部位特异性差异（双侧检验）进行了亚组分析。
总体而言，研究之间受体转换的发生率差异很大。对于 ERα、PR 和 HER2，我们发现随机效应模型汇总的阳性转为阴性转换百分比分别为 22.5%（95%置信区间 [CI] = 16.4%至 30.0%）、49.4%（95% CI = 40.5%至 58.2%）和 21.3%（95% CI = 14.3%至 30.5%）。阴性转为阳性转换百分比分别为 21.5%（95% CI = 18.1%至 25.5%）、15.9%（95% CI = 11.3%至 22.0%）和 9.5%（95% CI = 7.4%至 12.1%）。此外，ERα 不相符在中枢神经系统和骨转移中明显高于肝转移（20.8%，95%CI=15.0%至 28.0%和 29.3%，95%CI=13.0%至 53.5%，与 14.3%，95%CI=11.3%至 18.1%，P=0.008 和 P<0.001），PR 不相符在骨转移（42.7%，95%CI=35.1%至 50.6%，P<0.001）和肝转移（47.0%，95%CI=41.0%至 53.0%，P<0.001）中明显高于中枢神经系统转移（23.3%，95%CI=16.0%至 32.6%）。
在乳腺癌的疾病进展过程中，ERα、PR 和 HER2 的受体转换经常发生。需要进行大型前瞻性研究来评估受体转换对治疗效果和生存的影响。同时，强烈鼓励重新评估转移灶的受体状态。
