腋窝淋巴结转移乳腺癌患者的分子分型与临床病理特征和预后的关系

Association of molecular subtyping with clinicopathologic features and prognosis in breast cancer patients with axillary lymph node metastasis

目的:探讨腋窝淋巴结转移的乳腺癌患者的分子分型与临床病理特征和预后的关系。方法:回顾性分析181例可手术的腋窝淋巴结转移乳腺癌患者的临床病理资料,并对这些患者进行分子分型。所有患者的随访时间为44～68个月,中位随访时间为58个月。对乳腺癌患者的年龄、原发肿瘤大小、腋窝淋巴结转移个数和分子分型进行预后相关因素分析。结果:181例乳腺癌患者分成luminal型(105例,58.0%)、人表皮生长因子受体2(human epidermal growth factor receptor2,HER-2)过表达型(32例,17.7%)和basal-like型(44例,24.3%)。HER-2过表达型患者的原发肿瘤较大,腋窝淋巴结转移个数较多。Luminal型、basal-like型和HER-2过表达型患者的复发率分别为17.1%(18/105)、31.8%(14/44)和37.5%(12/32),差异有统计学意义(P=0.026);luminal型、basal-like型和HER-2过表达型患者的死亡率分别为6.7%(7/105)、13.6%(6/44)和18.8%(6/32),其中luminal型与非luminal型患者的死亡率差异有统计学意义(P=0.048)。Luminal型患者的5年无病生存率明显高于HER-2过表达型和basal-like型患者(P=0.025),luminal型患者的5年总生存率也明显高于HER-2过表达型患者(P=0.039)。预后相关因子分析结果显示,腋窝淋巴结转移个数和分子分型均是独立的预后因素(P<0.05)。结论:在未使用分子靶向药物治疗的情况下,在腋窝淋巴结转移的乳腺癌患者中,HER-2过表达型患者的预后最差,luminal型患者的预后最佳。腋窝淋巴结转移个数和分子分型均是乳腺癌患者的独立预后因素。

Objective： The aim of this study was to explore the association of different molecular subtypes with the clinicopathologic features and the prognosis in breast cancer patients with axillary lymph node metastasis. Methods： The clinicopathologic information of 181 operable breast cancer patients with axillary lymph node metastasis was retrospectively analyzed. These patients were classified into different groups according to molecular subtyping. All patients were followed-up with a median of 58 months （range： 44-68 months）. The multivariate analysis was performed to evaluate the prognostic indicators among the potential factors including age, primary tumor size, number of metastatic axillary lymph nodes and molecular subtype. Results： Of all 181 patients, 58.0% （1 05/1 81） were luminal subtype,24.3% （44/1 81） were basal-like subtype, and 17.7% （32/1 81） were HER-2 overexpression subtype. HER-2 overexpression was closely associated with increased tumor size and more positive lymph nodes. The relapse rates of luminal, basal-like and HER-2 overexpression subtypes were 17.1% （1 8/105）, 31.8% （14/44） and 37.5% （12/32）, respectively （P = 0.026）; the death rates of luminal, basal-like and HER-2 overexpression subtypes were 6.7% （7/105）, 13.6% （6/44） and 18.8% （6/32）, respectively （luminal vs non-luminal, P = 0.048）. The five-year disease-free survival rate of patients with luminal subtype was much higher than those of the patients with HER-2 overexpression and basal-like subtypes （log-rank test, P = 0.025）; the five-year overall survival rate of patients with luminal subtype was also much higher than that of patients with HER-2 overexpression subtype （log-rank test, P = 0.039）. COX proportional hazards model revealed that primary tumor size and the number of metastatic axillary lymph nodes were both independent prognostic indicators （P 〉 0.05）. Conclusion： In axillary lymph node-positive breast cancer patients not receiving targeted molecular therapy, the subtype of HER-2 overexpression has the worst prognosis while the subtype of luminal has the best. The primary tumor size and the number of metastatic axillary lymph nodes were both independent prognostic indicators for breast cancer patients.