Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Breast Cancer Res Treat. 2019 Jun;175(3):649-658. doi: 10.1007/s10549-019-05206-y. Epub 2019 Mar 27.
This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC).
We reviewed medical records of 160 patients receiving targeted therapy with PI3K/mTOR/CDK4/6 inhibitors to treat MBC (n = 160; 185 treatment occurrences). Clinicopathologic data, treatment details, and edema incidence were recorded.
Edema incidence was 43.1% (69/160) overall and 25.6% (41/160) in the upper extremity ipsilateral to the treated breast. In 185 therapy regimens administered, 6.8% of patients on a PI3K inhibitor, 8.8% of patients on an mTOR inhibitor, and 9.2% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting upper extremity edema. Further, 9.1% of patients on a PI3K inhibitor, 18.8% of patients on an mTOR inhibitor, and 10.5% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting edema elsewhere in the body. Multivariate logistic regression showed that, beyond the established breast cancer-related lymphedema (BCRL) risk factors [axillary lymph node dissection (Odds Ratio (OR) 2.69, p = 0.020), regional lymph node irradiation (OR 6.47, p < 0.001), and body-mass index ≥ 30 kg/m (OR 3.46, p = 0.006)], a relative decrease in serum albumin after 3 months of treatment increased risk of developing edema (OR 2.07, p = 0.062). Neither duration nor type of therapy were significant risk factors for edema.
PI3K/mTOR/CDK4/6 inhibitors may influence the development of edema, which may cause or exacerbate progression of BCRL in patients with MBC. The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL.
本研究评估了接受 PI3K/mTOR/CDK4/6 靶向治疗转移性乳腺癌（MBC）的患者发生水肿的情况。
我们回顾了 160 例接受 PI3K/mTOR/CDK4/6 抑制剂靶向治疗 MBC（n=160；185 次治疗）的患者的病历。记录了临床病理数据、治疗细节和水肿的发生率。
总水肿发生率为 43.1%（69/160），同侧上肢为 25.6%（41/160）。在 185 个治疗方案中，6.8%的患者使用 PI3K 抑制剂、8.8%的患者使用 mTOR 抑制剂、9.2%的患者使用 CDK4/6 抑制剂出现新的或恶化的上肢水肿。此外，9.1%的患者使用 PI3K 抑制剂、18.8%的患者使用 mTOR 抑制剂、10.5%的患者使用 CDK4/6 抑制剂出现新的或恶化的其他部位水肿。多变量逻辑回归显示，除了已确定的乳腺癌相关淋巴水肿（BCRL）危险因素[腋窝淋巴结清扫术（Odds Ratio（OR）2.69，p=0.020）、区域淋巴结放疗（OR 6.47，p<0.001）和体质量指数≥30 kg/m2（OR 3.46，p=0.006）]外，治疗后 3 个月血清白蛋白相对下降增加了发生水肿的风险（OR 2.07，p=0.062）。治疗持续时间和类型均不是水肿的显著危险因素。
PI3K/mTOR/CDK4/6 抑制剂可能会影响水肿的发生，这可能导致或加重 MBC 患者的 BCRL 进展。不同治疗方案之间水肿的发生率差异表明，需要对接受这些治疗的患者进行密切监测，尤其是那些有发生 BCRL 高风险的患者。
