Department of Obstetrics and Gynecology, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium.
Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium.
Breast Cancer Res Treat. 2021 Jan;185(1):183-194. doi: 10.1007/s10549-020-05935-5. Epub 2020 Sep 27.
In stage IV breast cancer, the efficacy of human epidermal growth factor receptor 2 (HER2) targeted therapies in cases with discordance in HER2 expression between primary and metastatic site is not well known. We studied progression free (PFS) and overall survival (OS) by HER2 concordance when treating women with taxane-trastuzumab (± pertuzumab) in first or second line and trastuzumab-emtansine (T-DM1) or capecitabine-lapatinib in later lines.
Retrospective monocentric study including all breast cancer patients receiving trastuzumab between January 2002 and September 2017 at the University Hospital in Leuven; we selected metastatic patients with an available HER2 status in primary and metastatic site. The Kaplan-Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model overall survival as a function group, correcting for possible confounders.
We included 74 patients; 46 had an unchanged HER2 status (positive/positive), 9 lost HER2 (positive/negative), while 19 acquired HER2 amplification (negative/positive). 25 out of 28 cases with a discordant HER2 status were positive for ER and/or PgR in the primary site. HER2 positive/negative cases had a significantly lower PFS for taxane-trastuzumab-(pertuzumab) (PFS = 5.5 months), compared to HER2 positive/positive (PFS 9 months, p = 0.01) and HER2 negative/positive (PFS 14 months, p = 0.01) patients. PFS for later line T-DM1 (n = 30) was significantly higher for the HER2 positive/positive group (PFS 6.0 months) than for the discordant groups HER2 negative/positive (PFS 1.0 month, p = 0.04) and HER2 positive/negative (PFS 1.5 month, p = 0.01). After correcting for possible confounders, the HER2 positive/negative group had a significantly worse OS compared to HER2 positive/positive (HR 0.19, 95% CI 0.08-0.44) and negative/positive (HR 0.15, 95% 0.06-0.38).
Conversion of HER2 status was seen in 28 out of 74 cases and was mostly observed in hormone receptor-positive tumors. In contrast to patients with HER2 loss, patients with a positive conversion of HER2 status derived substantial benefit from first line treatment with taxane-trastuzumab-(pertuzumab). This study highlights the importance of re-biopsying the metastatic lesion and changing treatment according to the last HER2 result.
在 IV 期乳腺癌中，原发灶和转移灶 HER2 表达不一致时，曲妥珠单抗（HER2 靶向治疗）的疗效尚不清楚。我们研究了在一线或二线使用紫杉烷曲妥珠单抗（±帕妥珠单抗）和二线使用曲妥珠单抗-美坦新（T-DM1）或卡培他滨-拉帕替尼治疗时，根据 HER2 一致性，无进展生存期（PFS）和总生存期（OS）。
回顾性单中心研究，纳入 2002 年 1 月至 2017 年 9 月在鲁汶大学医院接受曲妥珠单抗治疗的所有乳腺癌患者；我们选择了原发灶和转移灶均有 HER2 状态的转移性患者。采用 Kaplan-Meier 法估计 PFS/OS，采用对数秩检验分析组间差异。采用 Cox 模型检验组间差异，同时校正帕妥珠单抗。多变量 Cox 回归用于建模作为函数组的总生存期，校正可能的混杂因素。
我们纳入了 74 例患者；46 例 HER2 状态不变（阳性/阳性），9 例丢失 HER2（阳性/阴性），19 例获得 HER2 扩增（阴性/阳性）。28 例 HER2 状态不一致的病例中，25 例在原发灶中 ER 和/或 PgR 阳性。与 HER2 阳性/阳性（PFS 9 个月，p=0.01）和 HER2 阴性/阳性（PFS 14 个月，p=0.01）患者相比，HER2 阳性/阴性患者接受紫杉烷曲妥珠单抗（±帕妥珠单抗）的 PFS 明显更低（PFS=5.5 个月）。对于二线 T-DM1（n=30），HER2 阳性/阳性组的 PFS 明显高于不一致的 HER2 阴性/阳性组（PFS 1.0 个月，p=0.04）和 HER2 阳性/阴性组（PFS 1.5 个月，p=0.01）。在校正了可能的混杂因素后，与 HER2 阳性/阳性组相比，HER2 阳性/阴性组的 OS 明显更差（HR 0.19，95%CI 0.08-0.44）和阴性/阳性组（HR 0.15，95%CI 0.06-0.38）。
在 74 例病例中，有 28 例出现 HER2 状态的转化，主要发生在激素受体阳性肿瘤中。与 HER2 缺失的患者不同，HER2 状态阳性转化的患者从一线紫杉烷曲妥珠单抗（±帕妥珠单抗）治疗中获益显著。本研究强调了对转移灶进行再次活检并根据最后一次 HER2 结果改变治疗的重要性。
