Molecular Diagnostics
British Journal of Cancer (2010) 102, 1391–1396. doi:10.1038/sj.bjc.6605655 www.bjcancer.com
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
- 1Division of Haematology and Medical Oncology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
- 2Oncology Centre and Breast Care Centre, Hong Kong Sanatorium and Hospital, Hong Kong, China
Correspondence: Dr RJ Epstein, E-mail: repstein@stvincents.com.au
Received 23 December 2009; Revised 9 March 2010; Accepted 18 March 2010.
Abstract
background:
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).
methods:
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.
results:
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%).
conclusion:
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.
Keywords:
breast neoplasms; pre-invasive; intraductal; Ki-67; carcinogenesis; tumour progression