title: Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer.
abstract: Here, we determined the possible association of stromal caveolin-1 (Cav-1) levels with DCIS recurrence and/or progression to invasive breast cancer. An initial cohort of 78 DCIS patients with follow-up data was examined. As ER-positivity was associated with recurrence, we focused our analysis on this subset of 56 patients. In this group, we observed that DCIS progressed to invasive breast cancer in approximately 14% of the patient population (8/56), in accordance with an expected progression rate of 12-15%. Nearly ninety percent of DCIS patients (7/8) that underwent recurrence to invasive breast cancer had reduced or absent levels of stromal Cav-1. Remarkably, an absence of stromal Cav-1 (score = 0) was specifically associated with early disease progression to invasive breast cancer, with reduced time to recurrence and higher recurrence rate. All DCIS patients with an absence of stromal Cav-1 underwent some form of recurrence (5/5) and the majority (4/5) underwent progression to invasive breast cancer. This represents an overall cumulative incidence rate of 100% for recurrence and 80% for progression. An absence of stromal Cav-1 in DCIS lesions was also specifically associated with the presence of inflammatory cells. Conversely, ninety-seven percent of ER(+) DCIS patients (35/36) with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 mo), and 89% of such patients are estimated to remain free of invasive recurrence, even after 15 y. Thus, determination of stromal Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS patients.
authors.affiliation: Stem Cell Biology and Regenerative Medicine Center, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA. agnieszka.witkiewicz@jefferson.edu
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
authors.forename: Abhijit
authors.initials: A
authors.lastname: Dasgupta
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Nguyen
authors.forename: Chengbao
authors.initials: C
authors.lastname: Liu
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Kovatich
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Schwartz
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051242:Caveolin 1