Wu S Y, Tan Y, Guan Y S
Department of Head&Neck and Mammary Gland Oncology, West China Hospital of Sichuan University, Chengdu 610041, China.
Zhonghua Gan Zang Bing Za Zhi. 2016 Jun;24(6):422-8. doi: 10.3760/cma.j.issn.1007-3418.2016.06.006.
To investigate the clinical features and prognosis of patients with first-episode liver metastasis of different molecular subtypes of breast cancer and risk factors for liver metastasis of breast cancer.
A retrospective analysis was performed for 122 breast cancer patients with first-episode liver metastasis from January 2009 to January 2014. According to the cell surface receptors of breast cancer, these patients were divided into the four molecular subtypes of Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and triple-negative breast cancer (TNBC). The association of patients' age at initial diagnosis, body mass index (BMI), menstruation status, clinical TNM (cTNM) stage, levels of lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) at recurrence, liver metastasis, and treatment condition with the patients' prognosis were analyzed. The chi-square test and Fisher's exact test were used for categorical data, the Kaplan-Meier method was used for survival analysis, the log-rank test was used for univariate analysis of influencing factors, and the Cox regression model was used for multivariate analysis.
Among the 122 patients, 12 had Luminal A subtype, 61 had Luminal B subtype, 30 had HER2 overexpression subtype, and 19 had TNBC subtype. In the patients with Luminal A, Luminal B, HER2 overexpression, and TNBC subtypes, the median disease-free survival (DFS) was 32, 23, 16, and 10 months, respectively (P = 0.001), the median overall survival (OS) was 54, 35, 26, and 13 months, respectively (P = 0.003), and the median OS after liver metastasis was 30, 16, 10, and 9 months, respectively (P = 0.019). In HER2-positive patients, the application of trastuzumab in the past significantly prolonged the patients' DFS by 11 months and OS by 18 months (P < 0.05). The results of the multivariate analysis showed that cTNM stage, molecular subtype, and targeted therapy were independent influencing factors for DFS of breast cancer patients with liver metastasis (P < 0.05), and that BMI, increased LDH at recurrence, cTNM stage, molecular subtype, salvage chemotherapy, radiotherapy, and targeted therapy were independent influencing factors for OS of breast cancer patients with liver metastasis (P < 0.05). The patients with TNBC, HER2 overexpression, and Luminal B subtypes exhibited worse prognosis and had a risk of recurrence 15.97, 8.81, and 4.76 times higher than those with Luminal A subtype. The risk of death in the patients with TNBC, HER2 overexpression, and Luminal B subtypes was 8.42, 6.02, and 3.86 times that in those with Luminal A subtype.
The prognosis of breast cancer patients with first-episode liver metastasis is associated with the increase in LDH when liver metastasis occurs, BMI, cTNM stage, and molecular subtype. Compared with the patients with Luminal subtypes, those with HER2 overexpression and TNBC subtypes tend to develop liver metastasis in early stage and have a shorter OS. Salvage chemotherapy, targeted therapy, and radiotherapy can significantly improve the prognosis of patients with liver metastasis.
探讨不同分子亚型乳腺癌首次发生肝转移患者的临床特征、预后及乳腺癌肝转移的危险因素。
对2009年1月至2014年1月期间122例首次发生肝转移的乳腺癌患者进行回顾性分析。根据乳腺癌细胞表面受体，将这些患者分为腔面A型、腔面B型、人表皮生长因子受体2（HER2）过表达型和三阴性乳腺癌（TNBC）四种分子亚型。分析患者初诊年龄、体重指数（BMI）、月经状态、临床TNM（cTNM）分期、复发时乳酸脱氢酶（LDH）和碱性磷酸酶（ALP）水平、肝转移情况及治疗条件与患者预后的相关性。分类资料采用卡方检验和Fisher确切概率法，生存分析采用Kaplan-Meier法，影响因素单因素分析采用log-rank检验，多因素分析采用Cox回归模型。
122例患者中，腔面A型12例，腔面B型61例，HER2过表达型30例，TNBC型19例。腔面A型、腔面B型、HER2过表达型和TNBC型患者的无病生存期（DFS）中位数分别为32、23、16和10个月（P = 0.001），总生存期（OS）中位数分别为54、35、26和13个月（P = 0.003），肝转移后的OS中位数分别为30、16、10和9个月（P = 0.019）。在HER2阳性患者中，既往应用曲妥珠单抗显著延长患者DFS 11个月、OS 18个月（P < 0.05）。多因素分析结果显示，cTNM分期、分子亚型和靶向治疗是乳腺癌肝转移患者DFS的独立影响因素（P < 0.05），BMI、复发时LDH升高、cTNM分期、分子亚型、挽救性化疗、放疗和靶向治疗是乳腺癌肝转移患者OS的独立影响因素（P < 0.05）。TNBC型、HER2过表达型和腔面B型患者预后较差，复发风险分别是腔面A型患者的15.97、8.81和4.76倍。TNBC型、HER2过表达型和腔面B型患者的死亡风险分别是腔面A型患者的8.42、6.02和3.86倍。
首次发生肝转移的乳腺癌患者预后与肝转移时LDH升高、BMI、cTNM分期及分子亚型有关。与腔面亚型患者相比，HER2过表达型和TNBC型患者肝转移发生较早，OS较短。挽救性化疗、靶向治疗和放疗可显著改善肝转移患者的预后。
