Saitama Gamma Knife Center, San-ai Hospital, 4-35-17, Tajima, Sakura-ku, Saitama, 338-0837, Japan.
J Neurooncol. 2013 Apr;112(2):199-207. doi: 10.1007/s11060-013-1046-1. Epub 2013 Jan 8.
Advances in chemotherapy for breast cancer (BC) have prolonged overall survival, especially for patients with human epidermal growth factor receptor-2 (HER2) positive cancer. We evaluated the effectiveness and limitations of stereotactic radiosurgery (SRS) for brain metastases (BM) from BC in conjunction with molecular targeting chemotherapy. Outcomes were retrospectively reviewed in 80 consecutive patients who underwent gamma knife SRS for BM from BC between January 2009 and February 2012. The overall survival (OS), neurological death-free survival (NS) and local tumor control endpoints were calculated, and prognostic factors were investigated using proportional hazards models. In 40 patients with HER2-overexpression, treatment results were compared between two sub-groups: lapatinib-based therapy (24 patients) versus non-lapatinib-based therapy (16 patients). The rates of 1- and 2-year OS after SRS were 50 and 26 %, respectively. The median survival time (MST) was 11.4 months. HER2-overexpression (P < 0.001), recursive partitioning analysis class (P = 0.018) and total planning target volume on initial SRS (P = 0.004) were associated with OS. The MSTs in HER2-positive and -negative patients were 16.6 and 7.1 months, respectively (P = 0.001). The rates of 1- and 2-year NS were 90 and 78 %, respectively. The rates of 1- and 2-year local tumor control were 84 and 70 %, respectively. Factors associated with local tumor control included lesion volume (P < 0.001) and peripheral dose (P = 0.003). In sub-analysis of patients with HER2-overexpression, lapatinib-based chemotherapy was also associated with better local tumor control (P = 0.002). The 1-year local tumor control rate of the lapatinib group was significantly better than that of the non-lapatinib group (86 vs. 69 %, P < 0.001). SRS is a safe and effective management option for selected patients with BM from BC. Patients with HER2-overexpressing tumors were found to be a distinct subgroup for which a longer survival time can be expected. Synergistic anti-tumor effects of lapatinib on BM in conjunction with SRS were suggested.
乳腺癌（BC）的化疗进展延长了总生存期，尤其是对于人表皮生长因子受体 2（HER2）阳性癌症患者。我们评估了立体定向放射外科（SRS）联合分子靶向化疗治疗 BC 脑转移（BM）的有效性和局限性。对 2009 年 1 月至 2012 年 2 月期间接受伽玛刀 SRS 治疗的 80 例 BC 脑转移患者的回顾性结果进行了评估。计算了总生存率（OS）、神经死亡无进展生存率（NS）和局部肿瘤控制终点，并使用比例风险模型研究了预后因素。在 40 例 HER2 过表达的患者中，将两种亚组之间的治疗结果进行了比较：拉帕替尼治疗组（24 例）与非拉帕替尼治疗组（16 例）。SRS 后 1 年和 2 年的 OS 率分别为 50%和 26%。中位生存时间（MST）为 11.4 个月。HER2 过表达（P < 0.001）、递归分区分析分级（P = 0.018）和初始 SRS 时的总计划靶区体积（P = 0.004）与 OS 相关。HER2 阳性和阴性患者的 MST 分别为 16.6 个月和 7.1 个月（P = 0.001）。1 年和 2 年的 NS 率分别为 90%和 78%。1 年和 2 年的局部肿瘤控制率分别为 84%和 70%。与局部肿瘤控制相关的因素包括病变体积（P < 0.001）和周围剂量（P = 0.003）。在 HER2 过表达患者的亚组分析中，拉帕替尼为基础的化疗也与更好的局部肿瘤控制相关（P = 0.002）。拉帕替尼组的 1 年局部肿瘤控制率明显优于非拉帕替尼组（86%比 69%，P < 0.001）。SRS 是治疗 BC 脑转移患者的一种安全有效的选择。发现 HER2 过表达肿瘤患者是一个独特的亚组，可预期更长的生存时间。提示拉帕替尼联合 SRS 对 BM 具有协同抗肿瘤作用。
