探讨三阴性乳腺癌复发、转移的危险因素及时间分布规律。

采用回顾性病例分析方法，收集1998年1月1日至2008年12月31日中国医学科学院肿瘤医院收治的307例三阴性乳腺癌患者的临床病理资料及随访数据。采用χ²检验比较不同年龄、月经状态、乳腺癌/卵巢癌家族史、病理类型、肿瘤大小、淋巴结状态、TNM分期、脉管癌栓、手术方式、淋巴结清扫方式以及是否接受放射治疗者间复发、转移率的差异。采用Kaplan-Meier法绘制无浸润性疾病生存曲线，并用Log-rank法进行组间比较。为了校正混杂因素，采用Cox比例风险回归模型进行多因素分析。用寿命表法描绘复发、转移高峰曲线，研究三阴性乳腺癌复发、转移的时间分布规律。

中位随访137个月，共有103例(33.5%，103/307)出现复发、转移，其中首诊复发、转移部位以区域淋巴结转移(37.9%，39/103)、肺转移(32.0%，33/103)、骨转移(31.1%，32/103)和局部复发(26.2%，27/103)为主。单因素分析显示，TNM分期、肿瘤大小、淋巴结转移、脉管癌栓及手术方式是三阴性乳腺癌复发、转移的影响因素(χ²＝27.977、16.466、33.993、7.408、7.616，P均<0.050)。多因素分析显示，淋巴结转移和改良根治术是三阴性乳腺癌无浸润性疾病生存时间的独立危险因素(N₁期比N₀期：HR＝1.679, 95.0%CI: 1.049～2.687, P＝0.031; N₂期比N₀期：HR＝2.147, 95.0%CI: 1.205～3.826, P＝0.010; N₃期比N₀期：HR＝5.071, 95.0%CI: 2.988～8.604, P<0.001;保留乳房手术比改良根治术：HR＝0.348, 95.0%CI: 0.128～0.949，P＝0.039)。三阴性乳腺癌复发、转移风险的高峰曲线呈现四峰型，分别于术后第1、3、7、11年出现复发、转移高峰。第4个复发、转移高峰在淋巴结转移N₃分期中比较明显。

淋巴结转移和改良根治术是影响三阴性乳腺癌复发、转移的主要危险因素。不同于其他分子分型的乳腺癌复发、转移模式，三阴性乳腺癌的复发、转移风险曲线呈现四峰分布模式。淋巴结转移分期高的患者术后11年仍有较高的复发、转移风险。

To explore the risk factors and time distribution of recurrence and metastasis in triple negative breast cancer.

We retrospectively analyzed the clinicopathological data and follow-up data of 307 cases of triple negative breast cancer in Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 1998 to December 31, 2008. The categorical variables including age grouping, menstrual status, family history of breast cancer or ovarian cancer, pathological type, tumor size, lymph node metastasis, TNM stage, vascular tumor thrombus, surgical method, lymph node dissection method and radiotherapy were compared between groups using χ² test. Survival curves of invasive disease-free survival were drawn using the Kaplan-Meier method and comparison between groups was performed using log-rank test. In order to correct confounding factors, Cox proportional hazards model was used for multi-factor analysis. Life table method depicted the peak curve of recurrence and metastasis to study the time distribution of recurrence and metastasis in triple negative breast cancer.

By the end of follow-up (median follow-up time of 137 months), a total of 103 cases (33.5%, 103/307) had recurrence and metastasis. The sites of recurrence and metastasis in the initial diagnosis included regional lymph node metastasis (37.9%, 39/103), lung metastasis (32.0%, 33/103), bone metastasis (31.1%, 32/103) and local recurrence (26.2%, 27/103). Univariate analysis showed that TNM stage, tumor size, lymph node metastasis, vascular tumor thrombus and surgical method were the factors affecting recurrence and metastasis of triple negative breast cancer (χ²=27.977, 16.466, 33.993, 7.408, 7.616, all P<0.050). Multivariate analysis showed that lymph node metastasis and modified radical mastectomy were independent risk factors for invasive disease-free survival of triple negative breast cancer (N₁ vs N₀: HR=1.679, 95.0%CI: 1.049-2.687, P=0.031; N₂ vs N₀: HR=2.147, 95.0%CI: 1.205-3.826, P=0.010; N₃ vs N₀: HR=5.071, 95.0%CI: 2.988-8.604, P<0.001; breast conserving surgery vs modified radical mastectomy: HR=0.348, 95.0%CI: 0.128-0.949, P=0.039). The peak curve of the recurrence and metastasis risk of triple negative breast cancer presented a four-peak pattern. Recurrence and metastasis peaks occurred at the 1st, 3rd, 7th and 11th year after surgery. The fourth peak of recurrence and metastasis was more significant in stage N₃ of lymph node metastasis.

Lymph node metastasis and modified radical mastectomy are main risk factors affecting the recurrence and metastasis of triple negative breast cancer. Distinct from other molecular subtypes of breast cancer, triple negative breast cancer shows the four-peak pattern of recurrence and metastasis risk curve. The patients with higher stage of lymph node metastasis are still at high risk of recurrence and metastasis at the 11th year after surgery.