Timmer Marco, Werner Jan-Michael, Röhn Gabriele, Ortmann Monika, Blau Tobias, Cramer Christina, Stavrinou Pantelis, Krischek Boris, Mallman Peter, Goldbrunner Roland
Department of General Neurosurgery, University Hospital Cologne, Cologne, Germany
Department of General Neurosurgery, University Hospital Cologne, Cologne, Germany.
Anticancer Res. 2017 Sep;37(9):4859-4865. doi: 10.21873/anticanres.11894.
BACKGROUND/AIM: Knowing the molecular footprint of tumors is a precondition for personalized medicine. For breast cancer, targeted therapies are frequently based on the molecular status of the tissue gained from the primary tumor operation. However, it is unclear whether metastases in different organs maintain the same status.
We compared the estrogen- (ER), progesterone- (PgR) and HER2/neu receptor status of the primary tumor with brain metastases in a series of 24 consecutive breast cancer patients.
62.5-75% of patients exhibited a constant receptor status between the primary tumor and the brain metastasis, whereas discordance rates of 25-37.5% were found, depending on the receptor. The rate of ER and PgR expression was each 41.6% in the primary tumors and decreased to 12.5% and 16.6% in the brain metastases. In contrast, the rate for Her2+ tumors increased from 41.6% in primary breast cancer to 65.2% in the respective brain metastases. The Ki-67 proliferation index increased significantly from a mean of 21% at the primary tumor site to 60% in brain metastases (p<0.001). All anti-estrogen treated breast tumors lost the estrogen receptor expression in the brain metastases, whereas no Her2/neu conversions occurred after treatment with trastuzumab.
In summary, receptor conversion is frequent during disease progression. Therefore, the receptor status of the primary tumor is invalid for planning a therapy targeted against brain metastases, especially after hormone-therapy. In these cases, new tissue collection by biopsy or resection is mandatory for the selection of adequate therapeutic targets and accurate decision-making for systemic therapies.
背景/目的：了解肿瘤的分子特征是个性化医疗的前提。对于乳腺癌而言，靶向治疗通常基于原发肿瘤手术获取的组织分子状态。然而，不同器官的转移灶是否维持相同状态尚不清楚。
我们比较了24例连续乳腺癌患者原发肿瘤与脑转移灶的雌激素（ER）、孕激素（PgR）及HER2/neu受体状态。
62.5% - 75%的患者原发肿瘤与脑转移灶之间受体状态保持一致，而不一致率为25% - 37.5%，具体取决于受体类型。原发肿瘤中ER和PgR的表达率均为41.6%，在脑转移灶中分别降至12.5%和16.6%。相比之下，Her2+肿瘤的比例从原发性乳腺癌的41.6%增至相应脑转移灶的65.2%。Ki-67增殖指数从原发肿瘤部位的平均21%显著增至脑转移灶的60%（p<0.001）。所有接受抗雌激素治疗的乳腺肿瘤在脑转移灶中均失去雌激素受体表达，而使用曲妥珠单抗治疗后未发生Her2/neu转化。
总之，疾病进展过程中受体转换频繁。因此，原发性肿瘤的受体状态对于针对脑转移灶的治疗规划无效，尤其是在激素治疗后。在这些情况下，通过活检或切除获取新组织对于选择合适的治疗靶点及做出准确的全身治疗决策至关重要。
