Abstract 3262: Biomarkers of response to deslorelin in women at high risk of breast cancer
Abstract Women with BRCA1 or BRCA2 mutations have a high breast cancer (BC) risk. Breast density is an independent biomarker of BC risk. We demonstrated that deslorelin (D), a gonadotropin-releasing hormone agonist (GnRHA), reduced mammographic breast density among BRCA1 carriers (Weitzel, CCR 2007)...
Saved in:
| Published in: | Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.3262-3262 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract
Women with BRCA1 or BRCA2 mutations have a high breast cancer (BC) risk. Breast density is an independent biomarker of BC risk. We demonstrated that deslorelin (D), a gonadotropin-releasing hormone agonist (GnRHA), reduced mammographic breast density among BRCA1 carriers (Weitzel, CCR 2007). We report here on correlative studies in a Phase II chemoprevention study of intranasal D plus low-dose add-back estradiol and testosterone for 10 months in 10 premenopausal high-risk women. Pre- and post-study measures included mammographic and MRI breast density; serum hormone levels; breast tissue gene expression by Affymetrix GeneChip Human Genome U133 Plus 2.0 Array; Q-PCR to validate the top genes; analysis of sera by 2D-PAGE and LC-MS/MS Mass Spectrometry, validated by a marker specific ELISA. Nine 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). The top five differentially expressed genes in breast tissue were: FOS, EGR1, FABP3, COL3A1 and COL1A1. From seven protein spots up-regulated following treatment, 65 sera proteins were initially identified as response biomarkers, with two of these, adiponectin and Vitamin D-binding protein, predicted by Ingenuity Pathway Analyses (IPA) to have a direct role in reducing breast density by possibly altering stromal and epithelial tissue viability and fat metabolism. FOS was identified through IPA in the Vitamin D-binding protein network and both COL3A1 and COL1A1 were identified in the adiponectin network. Of the nine subjects two had an increase of ≥ 5% BMI and two had a decrease of ≥ 5% BMI. There was no significant correlation between adiponectin level changes and BMI changes.Tissue micro-array gene expression and proteomic analyses of sera identified changes in biomarkers that correlated with reduced breast density among young high-risk women receiving a GnRHA-based chemoprevention regimen.
Pre/Post Human Serum Adiponectin LevelsA_Pre: 0 MB_ Post: 10 MFold (Post/Pre)Log A (0M)Log B (10M)T-Test (p) pairedS10.4630.3860.835-0.335-0.4130.014S20.3760.4131.097-0.425-0.385S30.2620.3671.403-0.583-0.435S40.6640.8021.209-0.178-0.096S50.2450.6082.487-0.612-0.216S60.3150.7552.399-0.502-0.122S70.4130.7991.936-0.385-0.098S80.5750.6461.123-0.240-0.190S90.4360.7331.680-0.361-0.135Average1.574224
Citation Format: Jeffrey N. Weitzel, Michael F. Press, S |
|---|---|
| ISSN: | 0008-5472 1538-7445 |