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 ~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 months), and 89% of such patients are estimated to

remain free of invasive recurrence, even after 15 years. Thus, determination of stromal

Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS

patients.