title: Is there a low-grade precursor pathway in breast cancer?
abstract: BACKGROUND
  Newly proposed models of breast tumorigenesis suggest that low- and high-grade lesions have distinct tumor progression pathways. Our objective was to examine the relationship between histologic grade and molecular subtype in women with lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) who developed subsequent ipsilateral invasive breast cancers.
  
  
  METHODS
  Patients who underwent surveillance for classical LCIS (1994-2007) and those followed after lumpectomy±radiation for DCIS (1991-2004) who developed subsequent ipsilateral invasive cancers and had available tissue blocks were included. ER/PR/HER2 surrogates were used for molecular subtype.
  
  
  RESULTS
  Material was available for 27 patients with classical LCIS who developed ipsilateral invasive cancer (12 invasive ductal cancer [IDC], 14 invasive lobular, 1 mixed), and 26 patients with DCIS (12 low-grade [LG], 14 high-grade [HG]) who developed ipsilateral IDC. No difference in age at diagnosis or median time to invasive cancer existed between groups with LCIS and DCIS. When stratified by grade, 0 of 12 LG-DCIS developed LG-IDC (3 grade II; 9 grade III), and only 1 of 12 LCIS patients who developed IDC had LG-IDC. Thirteen (93%) patients with HG-DCIS developed HG-IDC. In contrast, molecular subtype was maintained in 23 of 27 (85%) cases of LCIS and in 18 of 26 (69%) cases of DCIS.
  
  
  CONCLUSIONS
  These data do not support a low-grade precursor pathway characterized by LCIS and LG-DCIS. ER/PR and HER2 status have a high rate of concordance between in situ and subsequent invasive lesions. Additional studies of metachronous in situ and invasive lesions are needed to better understand pathways of breast tumorigenesis.
authors.affiliation: Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA. kingt@mskcc.org
authors.forename: Tari A
authors.initials: TA
authors.lastname: King
authors.forename: Rita A
authors.initials: RA
authors.lastname: Sakr
authors.forename: Shirin
authors.initials: S
authors.lastname: Muhsen
authors.forename: Victor P
authors.initials: VP
authors.lastname: Andrade
authors.forename: Dilip
authors.initials: D
authors.lastname: Giri
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Van Zee
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human