赫突靶向治疗前后赫突表达不一致

　　根据既往研究报告，乳腺癌原发肿瘤与转移组织的HER2表达并不一致。不过，HER2靶向治疗前后HER2表达的一致性尚不明确。

　　2019年2月26日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表德国马德堡大学、雷根斯堡大学的研究报告，分析了原发性乳腺癌患者原发肿瘤与转移组织HER2表达不一致与HER2靶向治疗的相关性。

　　该研究对2005年1月～2016年12月有二次病理检查结果且未病理完全缓解的227例原发性未转移乳腺癌女性进行回顾分析。

　　结果发现，初次活检与新辅助或辅助治疗后二次活检的HER2表达不一致患者47例（占20.7%），并且与HER2靶向治疗存在显著相关性（P<0.0001）

• HER2表达转阳14例

• HER2表达转阴33例，其中接受HER2靶向治疗30例（90.9%）

• HER2表达一致180例，其中接受HER2靶向治疗32例（17.8%）

　　HER2表达不一致与一致的患者相比：

• 复发死亡风险高2.73倍（P=0.002）

• 总体死亡风险高2.02倍（P=0.136）

　　对于HER2过表达乳腺癌患者，HER2表达转阴比例：

• 曲妥珠单抗治疗后：47.3%

• 帕妥珠单抗治疗后：63.2%

　　此外，末次HER2靶向治疗至新辅助治疗后肿瘤手术切除或非同时转移灶活检的时间间隔，与肿瘤HER2表达显著变化相关。

　　术前治疗结束至手术切除的时间间隔：

• HER2表达转阴：中位23天（范围：5～81天）

• HER2表达一致：中位51天（范围：10～179天）

　　术后治疗结束至转移活检的时间间隔：

• HER2表达转阴：中位15天（范围：2～165天）

• HER2表达一致：中位478天（范围：7～2779天）

　　因此，该研究结果表明，抗HER2治疗和二次检测HER2时间间隔与HER2表达密切相关。

Breast Cancer Res Treat. 2019 Feb 26.

Loss of HER2 after HER2-targeted treatment.

Tanja Ignatov, Franceska Gorbunow, Holm Eggemann, Olaf Ortmann, Atanas Ignatov.

Otto-von-Guericke University, Magdeburg, Germany; University Medical Center, Regensburg, Germany.

PURPOSE: HER2 expression has been reported to be discordant between primary tumor and metastatic tissue.

PATIENTS AND METHODS: HER2 discordance and relation to HER2-targeted treatment was investigated in 227 patients with primary breast cancer.

RESULTS: HER2 discordance between primary biopsy and second biopsy after neoadjuvant or adjuvant treatment was observed in 20.7%. This discordance was related only to the use of HER2-targeted treatment: 30 of 33 (90.9%) women with downgraded HER2 expression underwent a HER2-targeted therapy, whereas in the group of patients with concordant HER2 expression, only 32 of 180 (17.8%) received HER2-targeted treatment (p<0.0001). HER2 discordance was associated with reduced disease-free survival but not overall survival. In a second cohort, including patients with HER2 overexpressing tumors, trastuzumab treatment was associated with change of HER2 expression from positive to negative in 47.3% of cases. Addition of pertuzumab increased the rate of HER2 loss up to 63.2%. Notably, the interval between last HER2-targeted treatment and the time of surgical excision of the tumor after neoadjuvant chemotherapy (NACT) or the biopsy of the metachronous metastasis was associated with a significant change in HER2 expression. The median time between NACT and the time of surgical excision was 23 days (range 5-81 days) for tumors with decreased HER2 expression and 51 days (range 10-179 days) for tumors with concordant HER2 expression. Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively.

CONCLUSION: The interval between anti-HER2 treatment and the determination of HER2 in second histology is strongly associated with HER2 expression.

KEYWORDS: Trastuzumab Breast cancer HER2

DOI: 10.1007/s10549-019-05173-4