Sulindac, a non-selective NSAID, reduces breast density in postmenopausal women with breast cancer treated with aromatase inhibitors

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.