Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer

Agnieszka K. Witkiewicz, Abhijit Dasgupta, Katherine H. Nguyen, Chengbao Liu, Albert J. Kovatich, Gordon F. Schwartz, Richard G. Pestell, Federica Sotgia, Hallgeir Rui, Michael P. Lisanti

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103 Scopus citations

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 ∼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.

Original languageEnglish (US)
Pages (from-to)1071-1079
Number of pages9
JournalCancer Biology and Therapy
Volume8
Issue number11
Publication statusPublished - Jun 1 2009

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Keywords

  • Caveolin-1
  • DCIS
  • Progression
  • Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Witkiewicz, A. K., Dasgupta, A., Nguyen, K. H., Liu, C., Kovatich, A. J., Schwartz, G. F., ... Lisanti, M. P. (2009). Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biology and Therapy, 8(11), 1071-1079.