近年来，随着PI3K、mTOR、CDK抑制剂等靶向药物的问世，转移性乳腺癌患者的生存率不断提高、生存时间不断延长。不过，乳腺癌相关生存问题解决之后，乳腺癌相关水肿问题日益突出。
2019年3月27日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表美国哈佛大学医学院、麻省总医院的研究报告，评估了转移性乳腺癌患者接受PI3K、mTOR、CDK靶向疗法的水肿发生风险。
该研究对2011年5月～2016年8月麻省总医院160例接受PI3K、mTOR、CDK抑制剂靶向治疗转移性乳腺癌患者的185次治疗记录进行回顾，对临床病理数据、治疗细节和水肿发生率进行分析。
结果发现，治疗前原有或治疗后新发水肿患者69例（43.1%），其中同侧上肢水肿患者41例（25.6%）。
其中，治疗前原有上肢水肿恶化或治疗后新发上肢水肿患者：
PI3K抑制剂：6.8%
mTOR抑制剂：8.8%
CDK抑制剂：9.2%
此外，其他部位治疗前原有水肿恶化或治疗后新发水肿患者：
PI3K抑制剂：9.1%
mTOR抑制剂：18.8%
CDK抑制剂：10.5%
多因素逻辑回归分析表明，除了已知的乳腺癌相关水肿风险因素，其他增加水肿风险的因素包括：
腋窝淋巴结清扫：水肿风险高2.69倍（P=0.020）
区域淋巴结放疗：水肿风险高6.47倍（P<0.001）
体重指数≥30kg/m²：水肿风险高3.46倍（P=0.006）
治疗3个月后血清白蛋白相对减少：水肿风险高2.07倍（P=0.062）
治疗持续时间和类型都不是水肿的重要风险因素。
因此，该研究结果表明，PI3K、mTOR、CDK抑制剂可能影响水肿发生，可能引起或加重转移性乳腺癌患者乳腺癌相关水肿。由于不同治疗方案的水肿发生率不同，故有必要对接受这些治疗方案的患者进行监测，尤其对那些乳腺癌相关水肿高风险患者。
Breast Cancer Res Treat. 2019 Mar 27.
Incidence of peripheral edema in patients receiving PI3K/mTOR/CDK4/6 inhibitors for metastatic breast cancer.
Kayla M. Daniell, Aditya Bardia, Fangdi Sun, Sacha A. Roberts, Cheryl L. Brunelle, Tessa C. Gillespie, Hoda E. Sayegh, George E. Naoum, Dejan Juric, Steven J. Isakoff, Donna M. Fitzgerald, Alphonse G. Taghian.
Massachusetts General Hospital, Harvard Medical School, Boston, USA; Massachusetts General Hospital, Boston, USA.
PURPOSE: This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC).
METHODS: 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.
RESULTS: 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/m2 (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.
CONCLUSION: 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.
KEYWORDS: Lymphedema; Edema; Breast cancer; Metastatic breast cancer; Targeted therapy
DOI: 10.1007/s10549-019-05206-y
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