Division of Breast Surgery, Chiba Cancer Center Hospital, 666-2 Nitona-Cho, Chuo-Ku, Chiba, Japan,
Breast Cancer. 2013 Oct;20(4):336-41. doi: 10.1007/s12282-012-0341-6. Epub 2012 Feb 25.
The systemic management of metastatic breast cancer (MBC) is usually based on ER or HER2 status of the primary tumor. However, the hormonal status or the overexpression of human epidermal growth factor 2 (HER2) may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or biological agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors in breast cancer patients. Another objective of the study was to examine the effect of the clinical therapy on the basis of HER2 expression in a metastatic tumor.
In our hospital between 1991 to December 2010, retrospectively, 156 patients had biopsy or surgical resection of their metastatic site. All sample were analyzed pathologically to confirm metastatic disease and, second, to evaluate HER2 status by immunohistochemistry or by FISH.
The recurrence lesions were resected from the breast or lymph node (n = 67, local lesion), brain (n = 27), lung (n = 16), liver (n = 20), bone (n = 16), and from the stomach, intestine, ovary, and uterus (n = 10). Loss, increase, or no change in HER2 overexpression was observed in 3, 5, and 92%, respectively. Positive changes of HER2 in metastatic sites were 3 (4%) local lesion, 3 (11%) brain, 1 (7%) lung, 0 (0%) liver, 2 (17%) bone, and 0 (0%) others. In 3 of these 8 patients, trastuzumab was administered. In 2 of 3 patients, trastuzumab achieved long stable disease. The negative conversion rate of HER2 expression in metastatic lesions was 37% in patients treated with trastuzumab and 6% in those not treated with trastuzumab, a significant difference between the two groups (P < 0.05).
The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. For patients with positive conversion of HER2 status, more treatment options may be available. On the other hand, the rate of loss of HER2 expression was high in patients treated with trastuzumab, suggesting that the results of biopsy may provide an opportunity to reconsider treatment strategies for these patients.
转移性乳腺癌（MBC）的系统治疗通常基于原发性肿瘤的 ER 或 HER2 状态。然而，由于长期使用内分泌治疗、化疗或生物制剂治疗转移性癌症，激素状态或人表皮生长因子 2（HER2）的过表达可能会在每个转移部位发生变化。本研究旨在探讨乳腺癌患者原发性和远处转移性肿瘤中 HER2 表达变化的频率。本研究的另一个目的是根据转移性肿瘤中 HER2 的表达情况检查临床治疗的效果。
在我们医院，1991 年至 2010 年 12 月间，回顾性地对 156 例患者的转移部位进行了活检或手术切除。所有样本均进行病理分析以确认转移疾病，并通过免疫组化或 FISH 评估 HER2 状态。
复发的病变取自乳房或淋巴结（n=67，局部病变）、脑（n=27）、肺（n=16）、肝（n=20）、骨（n=16）以及胃、肠、卵巢和子宫（n=10）。分别观察到 3%、5%和 92%的 HER2 过表达丢失、增加或无变化。HER2 在转移部位的阳性变化分别为 3 个（4%）局部病变、3 个（11%）脑、1 个（7%）肺、0 个（0%）肝、2 个（17%）骨和 0 个（0%）其他。在这 8 例患者中，有 3 例接受了曲妥珠单抗治疗。在接受曲妥珠单抗治疗的 3 例患者中，2 例达到了长期稳定的疾病。接受曲妥珠单抗治疗的转移性病变中 HER2 表达的阴性转化率为 37%，未接受曲妥珠单抗治疗的患者为 6%，两组间差异有统计学意义（P<0.05）。
本研究结果强调了在复发病灶中确认 HER2 表达的重要性。对于 HER2 状态阳性转化的患者，可能会有更多的治疗选择。另一方面，在接受曲妥珠单抗治疗的患者中，HER2 表达丧失的比例很高，这表明活检结果可能为这些患者重新考虑治疗策略提供机会。
