Abstract P5-18-11: Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situof the breast
Authors: Yonekura R , Osako T , Iwase T , Ogiya A , Ueno T , Ohno S , Akiyama F 
Published: May 2019

Background: By definition, ductal carcinoma in situ (DCIS) does not metastasize to the lymph nodes. However, since the introduction of molecular whole-node analysis using the one-step nucleic acid amplification (OSNA) assay for sentinel node (SN) biopsies, the number of DCIS patients with SN metastasis has increased. The clinical management of node-positive DCIS remains controversial because these patients can be treated as different stages based on the pathogenesis: e.g. occult invasive cancer with true nodal metastasis (T1N1) or true DCIS with iatrogenic dissemination of benign or tumor cells into lymph node (TisN0). In this retrospective cohort study, we aimed to elucidate the pathogenesis of nodal metastasis in DCIS and the clinical management of node-positive DCIS.

Patients and Methods: Subjects comprised of 427 patients with a routine postoperative diagnosis of DCIS who underwent SN biopsy using the OSNA assay between 2009 and 2012. The cut-off values of the OSNA assay for negative/positive results and micro/macrometastasis were defined at 250 and 5,000 copies/μL of cytokeratin 19 mRNA, respectively. In the SN-positive patients, all paraffin blocks containing the primary tumor were step-sectioned with 0.5-mm intervals until the tissue was exhausted, and all microscopic slides were examined for detecting occult invasions. Afterwards, the patients were classified into three cohorts based on the SN status and occult invasion: (1) no SN metastasis (TisN0), (2) SN metastasis without occult invasion (TisN1), and (3) SN metastasis with occult invasion (T1N1). Tumor characteristics including risk factors of occult invasions (e.g. large size, comedo-type), prognosis, and SN and non-SN status were compared among the three cohorts. The median follow-up time was 73.6 months.

Results: Of the 427 patients, 408 (95.6%) were SN-negative and 19 (4.4%) were SN-positive. By examining a total of 1,421 step-sectioned slides, 9 of the 19 SN-positive patients had occult invasions in the primary tumors. Overall, 408 (95.6%), 10 (2.3%), and 9 (2.1%) were classified into the TisN0, TisN1, and T1N1 cohorts, respectively. Either of adjuvant endocrine therapy or chemotherapy was given much more in the TisN1 and T1N1 cohorts than in the TisN0 cohort (80.0% and 88.9% vs. 5.4%).Other tumor characteristics were similar among the three cohorts. Although one patients had distant recurrence in the TisN0 cohort, none had locoregional or distant recurrences in the TisN1 and T1N1 cohorts. Regarding the lymph node status in the TisN1 and T1N1 cohorts, median tumor burdens in the SN are 590 and 310 copies/μL, and 2 (20.0%) and 2 (22.2%) patients had additional non-SN metastasis in the axillary dissection materials, respectively.

Conclusions: Tumor characteristics and prognosis were similar among the three cohorts albeit the TisN1 and T1N1 cohorts tended to received adjuvant systemic therapy. Moreover, the SN and non-SN status were similar between the TisN1 and T1N1 cohorts. Therefore, pathogenesis of nodal metastasis in DCIS cannot uniformly be explained, and tumors with different stages may be mixed in the node-positive DCIS. Thus, considering the favorable prognosis of node-positive DCIS, the clinical management should be determined on a case-by-case basis.

Citation Format: Yonekura R, Osako T, Iwase T, Ogiya A, Ueno T, Ohno S, Akiyama F. Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situof the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-11.