Molecular Diagnostics

BJC Open article

British Journal of Cancer (2010) 102, 1391–1396. doi:10.1038/sj.bjc.6605655
Published online 27 April 2010

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer

H Wong1, S Lau2, T Yau1, P Cheung2 and R J Epstein1,2

  1. 1Division of Haematology and Medical Oncology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
  2. 2Oncology Centre and Breast Care Centre, Hong Kong Sanatorium and Hospital, Hong Kong, China

Correspondence: Dr RJ Epstein, E-mail:

Received 23 December 2009; Revised 9 March 2010; Accepted 18 March 2010





The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).



We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.



Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).



IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.


breast neoplasms; pre-invasive; intraductal; Ki-67; carcinogenesis; tumour progression