【原】乳腺癌术前肿瘤指标升高预后意义

　　癌胚抗原（CEA）和癌症抗原15-3（CA15-3）等肿瘤标志物被广泛用于监测乳腺癌。不过，乳腺癌患者术前CEA和CA15-3水平升高的预后意义仍然存在争议。

　　2019年7月16日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表韩国建国大学医疗中心、梨花女子大学木洞医院、延世大学江南世博兰斯医院、高阳国家癌症中心、大邱岭南大学、仁川嘉泉大学、水原亚洲大学、高丽大学安岩医院的研究报告，分析了乳腺癌患者术前肿瘤标志物升高的预后意义。

　　该研究根据韩国乳腺癌学会登记中心数据库，对2000年1月～2015年12月接受手术的14万9238例患者临床病理指标进行回顾分析。

　　结果，对肿瘤大小、淋巴结分期、诊断时年龄、化疗等影响因素进行校正后，对于所有乳腺癌患者，与CA15-3和CEA水平正常相比：

• CA15-3和CEA水平升高：死亡风险高1.822倍（95%置信区间：1.266～2.622，P<0.001）

• CA15-3水平升高：死亡风险高1.948倍（95%置信区间：1.591～2.386，P<0.001）

• CEA水平升高：死亡风险高1.427倍（95%置信区间：1.164～1.75，P=0.001）

　　对于管腔A型乳腺癌患者，与CA15-3和CEA水平正常相比：

• CA15-3和CEA水平升高：死亡风险高2.141倍（95%置信区间：1.008～4.547，P=0.048）

• CA15-3水平升高：死亡风险高2.377倍（95%置信区间：1.579～3.577，P<0.001）

• CEA水平升高：死亡风险高1.793倍（95%置信区间：1.201～2.677，P=0.004）

　　对于管腔B型乳腺癌患者，与CA15-3和CEA水平正常相比：

• CA15-3和CEA水平升高：死亡风险高3.994倍（95%置信区间：2.229～7.155，P<0.001）

• CA15-3水平升高：死亡风险高2.022倍（95%置信区间：1.292～3.165，P=0.002）

• CEA水平升高：死亡风险相似（95%置信区间：0.726～1.902，P=0.51）

　　对于HER2阳性乳腺癌患者，与CA15-3和CEA水平正常相比：

• CA15-3和CEA水平升高：死亡风险相似（95%置信区间：0.648～6.353，P=0.224）

• CA15-3水平升高：死亡风险相似（95%置信区间：0.817～3.126，P=0.171）

• CEA水平升高：死亡风险高1.628倍（95%置信区间：1.062～2.495，P=0.025）

　　对于三阴性乳腺癌患者，与CA15-3和CEA水平正常相比：

• CA15-3和CEA水平升高：死亡风险相似（95%置信区间：0.023～1.153，P=0.069）

• CA15-3水平升高：死亡风险相似（95%置信区间：0.769～1.898，P=0.412）

• CEA水平升高：死亡风险相似（95%置信区间：0.5～1.76，P=0.843）

　　因此，根据该研究结果，不同乳腺癌亚型的术前CEA和CA15-3水平预后能力不同。术前CA15-3和CEA水平升高、CA15-3水平升高是管腔型乳腺癌的重要预后因素，但不是HER2阳性乳腺癌、三阴性乳腺癌的重要预后因素。术前CEA水平升高是管腔A型乳腺癌、HER2阳性乳腺癌的重要预后因素，但不是管腔B型乳腺癌、三阴性乳腺癌的重要预后因素。

Breast Cancer Res Treat. 2019 Jul 16.

The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients: data from the Korean Breast Cancer Society Registry.

Sang eun Nam, Woosung Lim, Joon Jeong, Seeyoun Lee, Jungeun Choi, HeungKyu Park, Yong Sik Jung, Seung Pil Jung, Soo Youn Bae.

Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea; Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; National Cancer Center, Goyang, Korea; Yeungnam University College of Medicine, Daegu, Korea; Gachon University, Incheon, Korea; Ajou University School of Medicine, Suwon, Korea; Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.

PURPOSE: Tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are widely used for monitoring breast cancer. However, the prognostic efficacy of preoperative elevations of CEA and CA15-3 levels in breast cancer patients remains controversial.

METHODS: We retrospectively analyzed the clinicopathological parameters of 149,238 patients in the Korean Breast Cancer Society Registry Database who underwent surgery between January 2000 and December 2015.

RESULTS: The patients with elevated CA15-3/CEA levels had worse overall survival (OS) than the patients with normal CA15-3/CEA levels. For the luminal A subtype, the CA15-3- and CEA-elevated group had a hazard ratio (HR) of 2.14 (95% CI 1.01-4.55). The CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68) compared to the normal group. For the luminal B subtype, the CA15-3- and CEA-elevated group had an HR of 3.99 (95% CI 2.23-7.16), whereas the CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68). For the HER2 subtype, elevated CEA level was the only independent prognostic factor. However, for the triple-negative breast cancer (TNBC) subtype, elevated preoperative CEA and CA15-3 levels were not significant prognostic factors for OS.

CONCLUSION: Preoperative CEA and CA15-3 levels showed varying prognostic ability according to breast cancer subtype. Preoperative CA15-3 and CEA elevation are significant prognostic factors for luminal breast cancer, but they were not significant factors for TNBC.

KEYWORDS: Breast cancer Tumor marker CA15-3 CEA Prognosis Subtypes Overall survival

DOI: 10.1007/s10549-019-05357-y