目的

临床上存在部分早期乳腺癌短时间内复发转移，其中包括导管原位癌伴微浸润（Ductal Carcinoma In Situ with Microinvasion, DCIS-MI）。由于其发病率较低且缺乏前瞻性临床研究，目前尚缺乏有针对性的相关诊治、预后的指南或共识。本研究旨在总结 DCIS-MI 患者的临床病理特点，分析临床实践中医生的管理模式、治疗选择及决策因素，归纳其不良预后因素及生存情况，为临床医师优化 DCIS-MI患者的治疗决策提供参考。

方法

回顾性分析 2012 年 11 月至 2022 年 8 月在我院及北京同仁医院就诊的术后DCIS-MI 患者。对临床病理学特征、治疗情况进行统计汇总。基于导管原位癌及微浸润的组织病理学特点和关键分子表达及在复发转移中的权重，构建复发风险因子及危险度评分标准，尝试量化该评分与临床医生治疗选择与预后的关系。主要观察指标为无病生存期（Disease Free Survival，DFS）和总生存期（Overall Survival，OS）。使用秩和检验比较复发风险评分在接受辅助化疗或抗 HER2 治疗组和未治疗组间的分布差异。使用 Kaplan-Meier 分析估计 DFS 和 OS，并使用对数秩检验比较生存曲线；使用对数秩检验和 Cox 回归分析进行单变量和多变量分析；P＜0.05 被认为具有统计学差异。采用 SPSS 27.0 软件包分析。

结果

一共入组了 60 例术后的 DCIS-MI 患者。平均确诊年龄 54.3 岁，平均肿瘤最大径为 29mm，多微浸润灶 12 例（20.0%），伴粉刺样坏死 27 例（45.0%）,原位癌成分核分级为高级别 54 例（90.0%），HER2 阳性 25 例（41.7%），HR 阳性 36 例（60.0%），Ki67 表达＞30%有 10 例（16.7%），腋窝淋巴结阳性 4 例（6.7%）。有 27 例（45.0%）患者接受了辅助化疗或抗 HER2 治疗，其中 16 例（59.3%）为 HR 阴性和（或）腋窝淋巴结阳性，包括所有腋窝淋巴结转移的患者。在 25 例 HER2阳性患者中有 10 例（40%）接受了辅助靶向治疗。在 24 例 HR 阴性患者中，有 14例（58.3%）接受了辅助化疗。在 36 例 HR 阳性患者中有 32 例（88.9%）接受了辅助内分泌治疗。复发风险评分在接受治疗与未接受治疗组间存在分布差异（P=0.003）。53 例患者可随访到生存信息。平均随访 38 个月后（中位随访时间 30 个月），共有 2 起 DFS 事件，5 年 DFS 率为 94.6%，所有患者均存活，OS 为 100%。与较差的DFS 显著相关的风险因素是 HER2 阳性/HR 阴性（P=0.01）和多微浸润灶（P＜0.001），但在多因素分析中未见统计学差异（P=0.529, 0.815）。复发风险评分≥17 分与较差的 DFS 显著相关（P=0.019）。

结论

DCIS-MI 患者在现行的治疗模式下具有良好的预后。HER2 阳性/HR 阴性、多微浸润灶是潜在的不良预后因素，复发风险评分≥17 分的患者可能生存较差。腋窝淋巴结阳性或复发风险评分≥16 分的患者接受辅助化疗联合或不联合抗 HER2 治疗可能带来生存获益；腋窝淋巴结阴性的复发风险评分＜16 分的患者，预估复发风险较小，需谨慎权衡强化辅助治疗的获益与风险。

Objective

Clinically, some early breast cancers recur and metastasize in a short time, including DCIS-MI. Due to its low incidence and the lack of prospective clinical studies, there is currently no guideline or consensus on its diagnosis, treatment, and prognosis. We aim to summarize the clinicopathological characteristics, analyze the management mode, treatment selection, and decision-making factors of doctors, evaluate the adverse prognostic factors and survival of patients, and provide reference for physicians to optimize the treatment decisions of DCIS-MI patients.

Method

Postoperative DCIS-MI patients in Beijing Hospital and Beijing Tongren Hospital from November 2012 to August 2022 were retrospective analyzed. The clinicopathological characteristics and treatments were statistically summarized. Based on the histopathology characteristics, the expression of key molecules of breast ductal carcinoma in situ and microinvasion, and their weight in recurrence and metastasis, the recurrence risk factor and risk score criteria were constructed, and the relationship between the score and treatment choice and prognosis was tried to quantify. The end points were DFS and OS. Use rank sum test to compare the distribution differences of recurrence risk scores between the group receiving adjuvant chemotherapy or anti HER2 treatment and the untreated group. Kaplan-Meier analysis was used to estimate DFS and OS, and the log-rank test was used to compare survival curves; Log-rank test and Cox regression model were used for univariate and multivariate analysis; P<0.05 was considered statistically significant. SPSS 27.0 software was used for analysis.

Result

A total of 60 postoperative DCIS-MI patients were enrolled. The average age of diagnosis was 54.3 years old, with an average maximum tumor diameter of 29mm. There were 12 cases (20.0%) with multiple microinvasive lesions, 27 cases (45.0%) with acne like necrosis, 54 cases (90.0%) with high nuclear grade, 25 cases (41.7%) with HER2 positive, 36 cases (60.0%) with HR positive, 10 cases (16.7%) with Ki67 expression >30%, and 4 cases (6.7%) with axillary lymph node positive. 27 patients (45.0%) received adjuvant chemotherapy or anti HER2 treatment, of which 16 patients (59.3%) were HR negative and/or axillary lymph node positive, including all patients with axillary lymph node metastasis. Out of 25 HER2 positive patients, 10 (40%) received adjuvant targeted therapy. Among the 24 HR negative patients, 14 (58.3%) received adjuvant chemotherapy. Out of 36 HR positive patients, 32 (88.9%) received adjuvant endocrine therapy. There was a distribution difference in the recurrence risk score between the treated and untreated groups (P=0.003). 53 patients can be followed up with survival information. After an average follow-up of 38 months (median follow-up time of 30 months), there were 2 DFS events, with a 5-year DFS rate of 94.6%. All patients survived, and the OS was 100%. The risk factors significantly associated with poor DFS were HER2 positive/HR negative (P=0.01) and multiple microinvasive lesions (P<0.001), but there was no statistical difference in multivariate analysis (P=0.529, 0.815). A recurrence risk score of ≥ 17 was significantly associated with poorer DFS (P=0.019).

Conclusion

DCIS-MI patients have a good prognosis under the current treatment mode. HER2 positive/HR negative, multiple microinvasive lesions are potential adverse prognostic factors, and patients with a recurrence risk score ≥17 may have poor survival. Patients with positive axillary lymph nodes or a recurrence risk score of ≥16 may benefit from adjuvant chemotherapy combined with or without anti HER2 therapy; Patients with a negative axillary lymph node whose recurrence risk score <16 have a lower estimated recurrence risk, and the benefits and risks of intensive adjuvant therapy need to be carefully weighed.