Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.
Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.
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DOI：
10.1016/j.ygyno.2020.07.016
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发表时间：
2020-10
影响因子：
4.7
通讯作者：
Fader AN
中科院分区：
文献类型：
--
作者：
Erickson BK;Najjar O;Damast S;Blakaj A;Tymon-Rosario J;Shahi M;Santin A;Klein M;Dolan M;Cimino-Mathews A;Buza N;Ferriss JS;Stone RL;Khalifa M;Fader AN
人表皮生长因子受体2 （HER2）已成为晚期和复发性子宫浆液性癌（USC）的重要预后和治疗靶点。肿瘤中HER2表达在早期疾病中的意义尚未确定。这项多中心队列研究包括2000-2019年接受I期南加州大学治疗的女性。收集了人口统计学、治疗、复发和生存数据。免疫组化（IHC）检测HER2，评分0-3 +。模棱两可的IHC结果（2+）进一步用荧光原位杂交（FISH）检测。HER2阳性定义为3+ IHC或FISH阳性。169名I期USC患者接受了HER2检测；26%为her2阳性。her2阳性组和阴性组在年龄、种族、分期、辅助治疗或随访时间方面没有显著差异。淋巴血管间隙浸润与her2阳性肿瘤相关（p=0.003）。中位随访50个月后，有43例（25.4%）复发。her2阳性队列的复发率明显更高（50.0% vs 16.8%, p<0.001）。HER2阳性肿瘤与较差的无进展（PFS）和总生存（OS）相关（p<0.001和p=0.024）。多因素分析显示，与HER2阴性肿瘤相比，HER2阳性肿瘤的PFS （aHR 3.50, 95%CI 1.84-6.67, p<0.001）和OS （aHR 2.00, 95%CI 1.04-3.88, p=0.039）较差。鉴于HER2阳性与更糟糕的复发和生存结果的显著相关性，HER2阳性似乎是I期子宫浆液性癌妇女的预后生物标志物。这些数据为抗her2定向治疗早期疾病的临床试验提供了支持。
Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. This multi-center cohort study included women with stage I USC treated from 2000–2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p=0.003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p<0.001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p<0.001 and p=0.024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84–6.67; p<0.001) and OS (aHR 2.00, 95%CI 1.04–3.88; p=0.039) compared to HER2-negative tumors. Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.
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影响因子：
4.7
作者：
Havrilesky, Laura J.;Secord, Angeles Alvarez;Gehrig, Paola A.
通讯作者：
Gehrig, Paola A.
影响因子：
8.8
作者：
Schwab, C. L.;Bellone, S.;English, D. P.;Roque, D. M.;Lopez, S.;Cocco, E.;Nicoletti, R.;Bortolomai, I.;Bonazzoli, E.;Ratner, E.;Silasi, D-A;Azodi, M.;Schwartz, P. E.;Rutherford, T. J.;Santin, A. D.
通讯作者：
Santin, A. D.
影响因子：
4
作者：
English, Diana P.;Bellone, Stefania;Schwab, Carlton L.;Bortolomai, Ileana;Bonazzoli, Elena;Cocco, Emiliano;Buza, Natalia;Hui, Pei;Lopez, Salvatore;Ratner, Elena;Silasi, Dan-Arin;Azodi, Masoud;Schwartz, Peter E.;Rutherford, Thomas J.;Santin, Alessandro D.
通讯作者：
Santin, Alessandro D.
影响因子：
8
作者：
Knuefermann, C;Lu, Y;Fan, Z
通讯作者：
Fan, Z
影响因子：
6.2
作者：
Fader, Amanda Nickles;Drake, Richard D.;Zanotti, Kristine M.
通讯作者：
Zanotti, Kristine M.