title: Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer.
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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Haematology and Medical Oncology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Lau
authors.forename: T
authors.initials: T
authors.lastname: Yau
authors.forename: P
authors.initials: P
authors.lastname: Cheung
authors.forename: R J
authors.initials: RJ
authors.lastname: Epstein
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002278:Carcinoma in Situ / Q000473:pathology; D044584:Carcinoma, Ductal / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000235:genetics; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017698:Postmenopause; D017697:Premenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D015996:Survival Rate; D017741:Survivors
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone