Providence Cancer Center, Earle A. Chiles Research Institute, 4805 NE Glisan St., Suite 6N40, Portland, OR, 97213, USA.
Memorial Sloan Kettering Cancer Center, 300 E 66th Street, New York, NY, 10065, USA.
Breast Cancer Res Treat. 2018 Jan;167(2):547-554. doi: 10.1007/s10549-017-4520-1. Epub 2017 Oct 6.
HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment.
From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0.
Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH.
In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.
荧光原位杂交（FISH）检测的 HER2 拷贝数通常相对于着丝粒计数探针 17（CEP17）报告。HER2/CEP17 比值可能会受到染色体 17 拷贝数变化的影响。在美国，每年约有 1900 例早期 HER2 阳性乳腺癌患者存在染色体 17 单体（m17）；然而，这些患者接受曲妥珠单抗治疗的疗效尚不清楚。在这里，我们回顾性地确定了 HER2 扩增的 I-III 期乳腺癌伴 m17，并对曲妥珠单抗治疗的影响进行了特征分析。
从 2000 年 1 月 1 日至 2011 年 6 月 1 日，我们确定了 99 例 HER2 扩增 m17 乳腺癌患者，其定义为核内 CEP17 信号<1.5，HER2/CEP17 比值≥2.0。
大多数 HER2 扩增 m17 患者接受曲妥珠单抗联合化疗（51%，n=50），而 31%（n=31）接受单纯化疗，18%（n=18）未接受化疗。与单独化疗或未化疗相比，曲妥珠单抗治疗的 4 年总生存率（OS）更高（分别为 100%、93%和 81%；p=0.005）。OS 不受雌激素/孕激素受体（ER/PR）状态、肿瘤分期或 FISH 阳性程度的影响。一部分根据标准免疫组织化学分期标准（0-1+）被认为是 HER2 阴性的患者，通过 FISH 检测发现 HER2 扩增。
在迄今为止报告的最大系列中，接受曲妥珠单抗治疗的 HER2 扩增 m17 癌症患者的结局与大型 III 期辅助曲妥珠单抗试验中 HER2 阳性患者相似，支持在这一患者群体中采用 HER2 靶向治疗的重要作用。
