Scheidegger Lisa, Frauchiger-Heuer Heike, Birindelli Esther, Papassotiropoulos Bärbel, Elfgen Constanze, Fansa Hisham, Maccio Umberto, Linsenmeier Claudia, Rordorf Tamara, Witzel Isabell, Varga Zsuzsanna
Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; Department of Anesthesiology and Perioperative Medicine, University Hospital Zurich, Zurich, Switzerland.
Breast Center, Department of Gynecology, University Hospital Zurich, Zurich, Switzerland; Comprehensive Cancer Center, University Hospital Zurich, Switzerland.
Hum Pathol. 2025 Aug 8;164:105902. doi: 10.1016/j.humpath.2025.105902.
Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer, detected mostly due to associated calcifications. Although non-invasive and primarily treated with surgical excision, recurrence as in situ or invasive form occurs in a substantial subset of DCIS patients. Microinvasion, defined as less than or equal to 1 mm invasive focus poses a diagnostic, biological and therapeutic dilemma, as the exact biological behavior of DCIS with or without microinvasion is controversially understood. In this retrospective study based on standardized pathology reports from a single center, we addressed the question if DCIS with or without microinvasive foci represents biologically one disease or two distinct entities.
We identified 148 patients with surgically treated DCIS and complete clinico-pathological data and follow-up information, 126 of 148 (85.1 %) pure form, 22 of 148 (14.9 %) with microinvasive foci. Events in follow-up (in-situ, invasive recurrent disease, breast cancer related death) were correlated with the presence of microinvasive foci and with pathological parameters (DCIS size, nuclear grade, the presence of necrosis, margin status, biomarkers, hormone receptors and Ki67 index) and clinical information (therapy modalities). Overall time-to-event-probability (TTE) was assessed with Kaplan Meier curves.
There was a total of 28 events (18.9 % of cohort). 12 of 148 (8.1 %) patients had recurrent DCIS, 16 of 148 (10.8 %) developed invasive breast cancer, 5 of 148 (3.4 %) patients died related to breast cancer in follow-up. DCIS with/without microinvasion did not differ significantly in TTE. There was a non-significant trend for worse 5-year breast cancer related death in DCIS with microinvasion. DCIS with microinvasion developed significantly more often in-situ or invasive recurrences in extensive disease (≥5 cm) (p = 0.040), with nuclear high grade (p = 0.045), with necrosis present (p = 0.045), with narrow resection margins (>1 mm) (p = 0.006), with younger age (≤50 years) in follow-up (p = 0.025) and in the absence of adjuvant radio- and/or endocrine therapy (p = 0.009, p = 0.034). No further factors such as calcification, positive margins, hormone receptor status had an impact on TTE on DCIS with or without microinvasive foci.
Our data shows that biological behavior of DCIS with microinvasive foci per se does not differ from pure DCIS in TTE. However, in-situ or invasive recurrences (total or ipsilateral) occur more often in microinvasive DCIS with extensive disease, with nuclear high grade, present necrosis, with narrow resection margins and in younger age in follow-up. These data warrant for further studies to understand the biology of DCIS with microinvasion and to evaluate specific therapy options different from pure DCIS potentially involving adjuvant modalities.
导管原位癌(DCIS)是一种非侵袭性乳腺癌,大多因相关钙化而被检测出。尽管其为非侵袭性且主要通过手术切除进行治疗,但相当一部分DCIS患者会出现原位复发或侵袭性复发。微浸润定义为侵袭灶小于或等于1毫米,这带来了诊断、生物学及治疗方面的难题,因为DCIS伴或不伴微浸润的确切生物学行为存在争议。在这项基于单一中心标准化病理报告的回顾性研究中,我们探讨了伴或不伴微浸润灶的DCIS在生物学上是一种疾病还是两种不同实体的问题。
我们确定了148例接受手术治疗的DCIS患者,他们拥有完整的临床病理数据及随访信息,其中148例中的126例(85.1%)为纯形式,148例中的22例(14.9%)伴有微浸润灶。随访中的事件(原位、侵袭性复发性疾病、乳腺癌相关死亡)与微浸润灶的存在以及病理参数(DCIS大小、核分级、坏死的存在、切缘状态、生物标志物、激素受体和Ki67指数)及临床信息(治疗方式)相关。采用Kaplan-Meier曲线评估总体事件发生时间概率(TTE)。
共有28起事件(占队列的18.9%)。148例中的12例(8.1%)患者出现DCIS复发,148例中的16例(10.8%)发展为侵袭性乳腺癌,148例中的5例(3.4%)患者在随访中死于乳腺癌。伴/不伴微浸润的DCIS在TTE方面无显著差异。伴有微浸润的DCIS在5年乳腺癌相关死亡方面有不显著的恶化趋势。伴有微浸润的DCIS在广泛病变(≥5厘米)(p = 0.040)、核分级高(p = 0.045)、存在坏死(p = 0.045)、切缘狭窄(>1毫米)(p = 0.006)、随访中年龄较轻(≤50岁)(p = 0.025)以及未接受辅助放疗和/或内分泌治疗(p = 0.009,p = 0.034)的情况下,原位或侵袭性复发更为常见。钙化、切缘阳性、激素受体状态等其他因素对伴或不伴微浸润灶的DCIS的TTE均无影响。
我们的数据表明,伴有微浸润灶的DCIS本身在TTE方面的生物学行为与纯DCIS并无差异。然而,伴有微浸润的DCIS在广泛病变、核分级高、存在坏死、切缘狭窄以及随访中年龄较轻的情况下,原位或侵袭性复发(全部或同侧)更为常见。这些数据值得进一步研究,以了解伴有微浸润的DCIS的生物学特性,并评估与纯DCIS不同的特定治疗方案,可能涉及辅助治疗方式。