Clin Cancer Res. 2021 Jun 10:clincanres.0732.2021. doi: 10.1158/1078-0432.CCR-21-0732. Online ahead of print.
ABSTRACT
PURPOSE: To evaluate the effect of sulindac, a non-selective anti-inflammatory drug, for activity to reduce breast density (BD), a risk factor for breast cancer.
EXPERIMENTAL DESIGN: An open-label Phase 2 study was conducted to test the effect of 12 months’ daily sulindac at 150 mg bid on change in percent BD in postmenopausal hormone receptor-positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by non-contrast MRI and reported as change in MRI percent BD (MRPD). A non-randomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12-months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated (SHG) microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy.
RESULTS: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% (95% CI, -14.6 to -4.7) at 12 months; an absolute decrease of -1.4% (95% CI, -2.5 to -0.3). A significant decrease in mean breast tissue collagen fiber straightness (p=0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI only observation group (N = 40).
CONCLUSIONS: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.
PMID:34112707 | DOI:10.1158/1078-0432.CCR-21-0732
