Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situ of the breast
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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.
KeywordsBreast cancer DCIS Lymph node metastasis OSNA Survival Parallel progression model
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).
Compliance with ethical standards
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.
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