Abstract P6-06-50: Obesity and the influence on tumor biology as determined by the intermediate risk 21-gene recurrence scores (RS) and the 70-gene breast cancer recurrence signature (70-GS) assay
Authors: Robinson P , Mai H , Guo R , Gaynor E , McCroskey Z , Ersahin C , Albain K , Lo S 
Published: August 2014

Abstract
BACKGROUND
Obesity is an apparent risk factor for postmenopausal breast cancer (BC), estrogen receptor (ER) positive BC, larger tumors, lymph node (LN) involvement, as well as recurrence of BC and BC death despite treatment. However, the specific mechanism of these increased risks remains unclear. Our prior work described the negative influence of metabolic syndrome on BC recurrence in patients assessed by a 21 gene recurrence score (RS) in the low risk and intermediate risk tertiles (Lakhani et al PSABCS 2012). The objective of this study was to analyze the interaction of obesity and BC biology in patients assessed by the 70 gene signature (70-GS) for BC recurrence and the 80 gene molecular subtyping.
METHODS
We studied consecutive patients with newly diagnosed ER positive, LN negative BC treated at Loyola University Medical Center between 2005 -2012 who had an intermediate RS. The 70-GS was done on these same paraffin-embedded tumor blocks for risk level and molecular subtype. Standard descriptive statistics are reported. Wilcoxon rank sum tests were performed for the comparison of BMI by groups defined by RS scores (≤24 vs ≥25) and the 70 gene signature assay (high risk vs low risk). In addition, Chi-squared test, or Fisher's exact test as appropriate, was used to examine the association between BMI tertiles and the 70GS or molecular subtype.
RESULTS
From 102 patients with intermediate RS, the 70-GS was successful in 89 samples. The average age was 61 years (range 41-79). The median body mass index (BMI) was 29 (range 18-53). There was a significant association between BMI and RS (p = 0.0110): median BMI = 28 in patients with RS ≤24; median BMI 33 in patients with RS ≥25. There was a significant association between BMI and the 70-GS (p = 0.0116). Median BMI 27 in low risk group; median BMI 32 in high risk group. There was a significant association between the 70-GS and BMI (p = 0.0190).
Association between the 70-GS and BMI70-GS RiskHealthy (18-25)Overweight (26-30)Obese (&gt;30)TotalHigh (n pts)1292950Low (n pts)15131139
There was a significant association between molecular subtype and BMI tertiles (p = 0.0803).
Association between molecular subtype and BMI tertiles HealthyOverweightObeseTotalLuminal A (n pts)14131239Luminal B (n pts)1392648
CONCLUSION
There is a striking interaction of obesity and BC biology as defined by the RS and 70-GS assays. Our data suggest that BC in obese women may have more aggressive tumor biology and higher risk of recurrence than BC in those with a low BMI. Further molecular characterization of the BC from obese patients may elucidate the role obesity plays in BC development and progression, as well as provide rationale for targeted therapeutic trials. Clinical trials targeting known carcinogenic pathways related to obesity (such as metformin and statins) are ongoing. Several genes in the 70-GS are the same genes expressed in obese patients. Additional studies examining the prognostic and predictive value of the 70-GS need to be conducted for this patient population.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-50.