Ductal carcinoma in situ (DCIS)—preinvasive breast cancer—with lymph node metastasis can clinically be treated as different stages: occult invasive cancer with true metastasis (T1N1) or pure DCIS with iatrogenic dissemination (TisN0). In this retrospective cohort study, we aimed to elucidate the prognostic impact and possible pathogenesis of nodal metastasis in DCIS to improve clinical management.
Subjects were comprised of 427 patients with routine postoperative diagnosis of DCIS who underwent sentinel node (SN) biopsy using molecular whole-lymph-node analysis. Clinicopathological characteristics and prognosis were compared between SN-positive and -negative patients. Primary tumour tissues of SN-positive patients were exhaustively step-sectioned to detect occult invasions, and predictive factors for occult invasion were investigated. Median follow-up time was 73.6 months.
Of the 427 patients, 19 (4.4%) were SN-positive and 408 (95.6%) were SN-negative. More SN-positive patients received adjuvant systemic therapy than SN-negative patients (84.2% vs. 5.4%). Seven-year distant disease-free survivals were favourable for both cohorts (SN-positive, 100%; SN-negative, 99.7%). By examining 1421 slides, occult invasion was identified in 9 (47.4%) of the 19 SN-positive patients. Tumour burdens in SN and incidence of non-SN metastasis were similar between patients with and without occult invasion, and no predictive factor for occult invasion was found.
Node-positive DCIS has favourable prognosis with adjuvant systemic therapy. Half of the cases may be occult invasive cancer with true metastasis. In practical settings, clinicians may have to treat these tumours as node-positive small invasive cancers because it is difficult to predict the pathogenesis without exhaustive primary tumour sectioning.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM (2004) Ductal carcinoma in situ of the breast. N Engl J Med 350:1430–1441. https://doi.org/10.1056/NEJMra031301
Ansari B, Ogston SA, Purdie CA, Adamson DJ, Brown DC, Thompson AM (2008) Meta-analysis of sentinel node biopsy in ductal carcinoma in situ of the breast. Br J Surg 95:547–554. https://doi.org/10.1002/bjs.6162
El Hage Chehade H, Headon H, Wazir U, Abtar H, Kasem A, Mokbel K (2017) Is sentinel lymph node biopsy indicated in patients with a diagnosis of ductal carcinoma in situ? A systematic literature review and meta-analysis. Am J Surg 213:171–180. https://doi.org/10.1016/j.amjsurg.2016.04.019
Osako T, Iwase T, Kimura K, Horii R, Akiyama F (2013) Detection of occult invasion in ductal carcinoma in situ of the breast with sentinel node metastasis. Cancer Sci 104:453–457. https://doi.org/10.1111/cas.12095
Osako T, Iwase T, Kimura K, Masumura K, Horii R, Akiyama F (2012) Incidence and possible pathogenesis of sentinel node micrometastases in ductal carcinoma in situ of the breast detected using molecular whole lymph node assay. Br J Cancer 106:1675–1681. https://doi.org/10.1038/bjc.2012.168
NCCN (2018) National comprehensive cancer network clinical practice guidelines in oncology. Breast Cancer ver. 1, 2018
Zetterlund L, Stemme S, Arnrup H, de Boniface J (2014) Incidence of and risk factors for sentinel lymph node metastasis in patients with a postoperative diagnosis of ductal carcinoma in situ. Br J Surg 101:488–494. https://doi.org/10.1002/bjs.9404
Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, Kato Y, Tsuda H, Ueda S, Sato K, Tamaki Y, Noguchi S, Kataoka TR, Nakajima H, Komoike Y, Inaji H, Tsugawa K, Suzuki K, Nakamura S, Daitoh M, Otomo Y, Matsuura N (2007) One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 13:4807–4816. https://doi.org/10.1158/1078-0432.CCR-06-2512
Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, Sato K, Ueda S, Mano M, Masuda N, Takeda M, Tsujimoto M, Yoshidome K, Inaji H, Nakajima H, Komoike Y, Kataoka TR, Nakamura S, Suzuki K, Tsugawa K, Wakasa K, Okino T, Kato Y, Noguchi S, Matsuura N (2009) Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res 15:2879–2884. https://doi.org/10.1158/1078-0432.CCR-08-1881
Osako T, Iwase T, Kimura K, Yamashita K, Horii R, Akiyama F (2011) Accurate staging of axillary lymph nodes from breast cancer patients using a novel molecular method. Br J Cancer 105:1197–1202. https://doi.org/10.1038/bjc.2011.350
Osako T, Iwase T, Kimura K, Yamashita K, Horii R, Yanagisawa A, Akiyama F (2011) Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer: a comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology. Cancer 117:4365–4374. https://doi.org/10.1002/cncr.26060
Amin MB (2018) American Joint Committee on cancer cancer staging manual, 8th edn. Springer, New York
Osako T, Iwase T, Ushijima M, Horii R, Fukami Y, Kimura K, Matsuura M, Akiyama F (2014) Incidence and prediction of invasive disease and nodal metastasis in preoperatively diagnosed ductal carcinoma in situ. Cancer Sci 105:576–582. https://doi.org/10.1111/cas.12381
Brennan ME, Turner RM, Ciatto S, Marinovich ML, French JR, Macaskill P, Houssami N (2011) Ductal carcinoma in situ at core-needle biopsy: meta-analysis of underestimation and predictors of invasive breast cancer. Radiology 260:119–128. https://doi.org/10.1148/radiol.11102368
Bleiweiss IJ, Nagi CS, Jaffer S (2006) Axillary sentinel lymph nodes can be falsely positive due to iatrogenic displacement and transport of benign epithelial cells in patients with breast carcinoma. J Clin Oncol 24:2013–2018. https://doi.org/10.1200/jco.2005.04.7076
Moore KH, Thaler HT, Tan LK, Borgen PI, Cody HS 3rd (2004) Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma: biologic metastasis or procedural artifact? Cancer 100:929–934. https://doi.org/10.1002/cncr.20035
Tvedskov TF, Jensen MB, Kroman N, Balslev E (2012) Iatrogenic displacement of tumor cells to the sentinel node after surgical excision in primary breast cancer. Breast Cancer Res Treat 131:223–229. https://doi.org/10.1007/s10549-011-1720-y
Diaz LK, Wiley EL, Venta LA (1999) Are malignant cells displaced by large-gauge needle core biopsy of the breast? AJR Am J Roentgenol 173:1303–1313
Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, Foster R, Gardner B, Lerner H, Margolese R, Poisson R, Shibata H, Volk H, et.al (1983) Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 52:1551–1557
Iqbal J, Ginsburg O, Giannakeas V, Rochon PA, Semple JL, Narod SA (2017) The impact of nodal micrometastasis on mortality among women with early-stage breast cancer. Breast Cancer Res Treat 161:103–115. https://doi.org/10.1007/s10549-016-4015-5
Osako T, Iwase T, Ushijima M, Yonekura R, Ohno S, Akiyama F (2017) A new molecular-based lymph node staging classification determines the prognosis of breast cancer patients. Br J Cancer 117:1470–1477. https://doi.org/10.1038/bjc.2017.311
Newman EL, Kahn A, Diehl KM, Cimmino VM, Kleer CA, Chang AE, Newman LA, Sabel MS (2006) Does the method of biopsy affect the incidence of sentinel lymph node metastases? Breast J 12:53–57. https://doi.org/10.1111/j.1075-122X.2006.00179.x
Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9:302–312. https://doi.org/10.1038/nrc2627
Narod SA, Sopik V (2018) Is invasion a necessary step for metastases in breast cancer? Breast Cancer Res Treat 169:9–23. https://doi.org/10.1007/s10549-017-4644-3
We thank Drs. Masujiro Makita, Seiichiro Nishimura, Yumi Miyagi, Kotaro Iijima, Hidetomo Morizono, Kiyomi Kimura, and Takehiko Sakai (Breast Oncology Center, the Cancer Institute Hospital) for providing clinical samples, and Mr. Motoyoshi Iwakoshi (Division of Pathology, the Cancer Institute) for sectioning primary tumour tissues.
This work was supported in part by a Grant-in-Aid for Young Scientists (B) (No. 21791264) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology and a Research Grant from the Foundation for the Promotion of Cancer Research in Japan (to Tomo Osako).
Conflict of interest
Futoshi Akiyama received consulting fee from Sysmex Corporation paid to the Japanese Foundation for Cancer Research. The other authors declare no conflicts of interest.
This study was approved by the Institutional Review Board of the Cancer Institute Hospital (Reference Nos. 2011-1015 and 2012-1061), and performed in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
The written general consent was obtained from each of the patients.
About this article
Cite this article
Yonekura, R., Osako, T., Iwase, T. et al. Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situ of the breast. Breast Cancer Res Treat 174, 103–111 (2019). https://doi.org/10.1007/s10549-018-5068-4
- Breast cancer
- Lymph node metastasis
- Parallel progression model