近年来，由于认识到乳腺钼靶检出导管原位癌的过度诊断和过度治疗，故正在进行的临床研究（LORIS、LORD、COMET）将非高分级导管原位癌女性随机分组，接受积极监测（定义为影像监测±内分泌疗法）或标准外科手术。然而，对于风险较低的乳腺导管原位癌患者，如果浸润癌发生风险被低估，那么可能妨碍积极监测。
2017年7月12日，《美国医学会杂志外科学分册》在线发表加利福尼亚罗马林达大学医学院的全国癌症数据库队列回顾研究报告，对临床诊断非高分级导管原位癌患者发生浸润癌被低估而妨碍积极监测的相关因素进行了调查，发现22.2%的临床诊断非高分级导管原位癌患者被最终手术切除病理诊断为浸润癌。与升级为浸润癌诊断显著相关的因素包括：年轻、激素受体阴性、共病（合并症）较多、年收入较高、在最近一年内被诊断、在学术机构接受治疗。
该队列回顾研究使用全国癌症数据库记录，入组37544例1998年1月1日～2012年12月31日临床诊断非高分级导管原位癌进行明确手术治疗的40～99岁（平均年龄59.3±12.4岁）女性患者，并于2015年11月1日～2017年2月4日进行数据分析，根据最终手术病理结果，对诊断升级为浸润癌与诊断为导管原位癌的患者进行比较。
结果发现，根据最终病理检查结果，8320例（22.2%）为浸润癌。浸润癌的尺寸较小（肿瘤大小0.5～1.0、1.0～2.0、2.0～5.0、＞5.0cm与≤0.5cm相比，比值比分别为0.73、0.42、0.19、0.11，95%置信区间：0.67～0.79、0.39～0.46、0.17～0.22、0.08～0.15），分级较低（中与低相比，比值比：0.75，95%置信区间：0.69～0.80）。
多因素逻辑回归分析表明，与根据最终病理学结果升级为浸润癌诊断显著相关的因素：
年轻（60～79、≥80岁与40～49岁相比，比值比：0.84、0.76，95%置信区间：0.77～0.92、0.64～0.91）
雌激素受体阴性（阳性与阴性相比，比值比：0.39，95%置信区间：0.34～0.43）
在学术机构治疗（学术与社区相比，比值比：2.08，95%置信区间：1.82～2.38）
年收入较高（＞6.3万美元与＜3.8万美元相比，比值比：1.14，95%置信区间：1.02～1.28）
因此，选择患者对导管原位癌进行积极监测时，根据最终病理学结果，除了肿瘤生物学因素，还应该考虑可能与浸润癌相关的社会人口统计学因素。随机分组进行积极监测时，需要注意可能有相当大比例的非高分级导管原位癌患者为浸润癌。
JAMA Surg. 2017 Jul 12. [Epub ahead of print]
Factors Associated With Underestimation of Invasive Cancer in Patients With Ductal Carcinoma In Situ: Precautions for Active Surveillance.
Chavez de Paz Villanueva C, Bonev V, Senthil M, Solomon N, Reeves ME, Garberoglio CA, Namm JP, Lum SS.
Loma Linda University School of Medicine, Loma Linda, California.
This cohort study uses the National Cancer Database to examine the factors associated with underestimation of invasive cancer in patients with a clinical diagnosis of non-high-grade DCIS that would preclude active surveillance.
QUESTION: What factors are associated with underestimation of invasive cancer in patients presenting with low-risk ductal carcinoma in situ that would preclude active surveillance?
FINDINGS: In this cohort study using the National Cancer Database, 22.2% of patients with a clinical diagnosis of non-high-grade ductal carcinoma in situ were found to have invasive carcinoma based on final pathologic findings at surgical excision. Factors that were significantly associated with an upgraded diagnosis of invasive carcinoma included younger age, negative hormone receptor status, more comorbidities, higher annual income, diagnosis in a more recent year, and treatment at an academic facility.
MEANING: When selecting patients for active surveillance of ductal carcinoma in situ, consideration should be given to sociodemographic and biological factors that may be associated with underlying invasive cancer.
IMPORTANCE: Recent recognition of the overdiagnosis and overtreatment of ductal carcinoma in situ (DCIS) detected by mammography has led to the development of clinical trials randomizing women with non-high-grade DCIS to active surveillance, defined as imaging surveillance with or without endocrine therapy, vs standard surgical care.
OBJECTIVE: To determine the factors associated with underestimation of invasive cancer in patients with a clinical diagnosis of non-high-grade DCIS that would preclude active surveillance.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using records from the National Cancer Database from January 1, 1998, to December 31, 2012, of female patients 40 to 99 years of age with a clinical diagnosis of non-high-grade DCIS who underwent definitive surgical treatment. Data analysis was conducted from November 1, 2015, to February 4, 2017.
EXPOSURES: Patients with an upgraded diagnosis of invasive carcinoma vs those with a diagnosis of DCIS based on final surgical pathologic findings.
MAIN OUTCOMES AND MEASURES: The proportions of cases with an upgraded diagnosis of invasive carcinoma from final surgical pathologic findings were compared by tumor, host, and system characteristics.
RESULTS: Of 37544 women (mean [SD] age, 59.3 [12.4] years) presenting with a clinical diagnosis of non-high-grade DCIS, 8320 (22.2%) had invasive carcinoma based on final pathologic findings. Invasive carcinomas were more likely to be smaller (>0.5 to ≤1.0 cm vs ≤0.5 cm: odds ratio [OR], 0.73; 95% CI, 0.67-0.79; >1.0 to ≤2.0 cm vs ≤0.5 cm: OR, 0.42; 95% CI, 0.39-0.46; >2.0 to ≤5.0 cm vs ≤0.5 cm: OR, 0.19; 95% CI, 0.17-0.22; and >5.0 cm vs ≤0.5 cm: OR, 0.11; 95% CI, 0.08-0.15) and lower grade (intermediate vs low: OR, 0.75; 95% CI, 0.69-0.80). Multivariate logistic regression analysis demonstrated that younger age (60-79 vs 40-49 years: OR, 0.84; 95% CI, 0.77-0.92; and ≥80 vs 40 to 49 years: OR, 0.76; 95% CI, 0.64-0.91), negative estrogen receptor status (positive vs negative: OR, 0.39; 95% CI, 0.34-0.43), treatment at an academic facility (academic vs community: OR, 2.08; 95% CI, 1.82-2.38), and higher annual income (>$63000 vs <$38000: OR, 1.14; 95% CI, 1.02-1.28) were significantly associated with an upgraded diagnosis of invasive carcinoma based on final pathologic findings.
CONCLUSIONS AND RELEVANCE: When selecting patients for active surveillance of DCIS, factors other than tumor biology associated with invasive carcinoma based on final pathologic findings may need to be considered. At the time of randomization to active surveillance, a significant proportion of patients with non-high-grade DCIS will harbor invasive carcinoma.
PMID: 28700803
DOI: 10.1001/jamasurg.2017.2181
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