Abstract 3557: Reduced ovarian hormones & reduced mammographic & MRI determined breast density in BRCA carriers following a hormonal chemo-prevention regimen of gonadotropin releasing hormone agonist (GnRHA) & low-dose add-back estrogen & testosterone

Abstract

Abstract Young women at high risk of breast and/or ovarian cancer due to a BRCA mutation need risk-reducing options that preserve childbearing capacity. Purpose: Correlate changes in breast tissue determined by magnetic resonance imaging (MRI) & mammography with ovarian hormone levels following GnRHA treatment. Methods: In this prospective phase 2 biomarker chemoprevention trial, 10 premenopausal high-risk women, mean age 29.4 (21-43), were treated with intranasal GnRHA (deslorelin), low-dose add-back estradiol & testosterone once daily for 10 months. MPA was given for 10 days starting Day 140. Serum hormone levels were measured pre-administration of study drugs on Day 1, 29, 169 & 300. All participants underwent mammography, breast MRI & breast biopsy before & after 300 days of treatment. Mammographic density was measured & compared to volumetric breast density from MRI at both time points for all participants & fibroglandular tissue volume was also determined. Results: Significant decreases (p < .05) were shown in estradiol (-61%) and testosterone (-41%) over time. Nine out of 10 participants showed a mean reduction in MRI volumetric breast density of 17.3% (p=0.045), a mean reduction in MRI fibroglandular volume of 15.1% (p=0.041) and a mean reduction in mammographic density of 31.9% (p=0.0033). Conclusion: Changes in breast tissue composition were significant after 10 months of hormonal chemoprevention, validating the proof of principle that density as a risk biomarker can be manipulated in BRCA carriers. We documented reduction in breast density by both mammographic and MRI assessment. While greater quantitative change in density was detected by mammography, MRI yields additional qualitative structural observations. Our findings confirm that MRI can be used to measure hormonal chemoprevention effects in women at high-risk of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3557. doi:1538-7445.AM2012-3557