B98

Background:
 >Mutations in the BRCA1 and BRCA2 genes result in a greatly increased risk of developing breast cancer at a young age. However, little is known about how lifestyle factors that influence breast cancer risk in premenopausal women affect women with gene mutations. Previous research in premenopausal women suggests an inverse relationship between body-mass index (BMI) and breast cancer risk. This relationship is yet to be fully determined in women with BRCA1 and BRCA2 mutations. Thus, the primary aim of this small pilot study is to examine whether BMI is associated with breast cancer in premenopausal women with mutations in the BRCA1 and BRCA2 genes.
 >Materials and Methods:
 >Clinical information and tumor pathology were examined in 251 premenopausal women seen for genetic risk assessment and testing at MD Anderson Cancer Center’s Clinical Cancer Genetics Program. Height and weight information taken within 3 months of the participants’ diagnosis of invasive breast cancer was used to calculate BMI. Women with a BMI of ≥ 30 were characterized as obese; women with a BMI < 30 were considered non-obese. Pathology reports were reviewed for each tumor to determine Black’s modified nuclear grade, estrogen receptor (ER) status, progesterone receptor (PR) status, and Her2/Neu protein expression status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Fisher’s exact tests and Wilcoxon sum-rank tests were used to determine significant differences between groups.
 >Results:
 >Of the 251 women, 31 tested positive for a BRCA gene mutation (BRCA+) and 220 tested negative for a mutation (BRCA-). Twenty-two BRCA+ women had a mutation in the BRCA1 gene; nine BRCA+ women had a mutation in the BRCA2 gene. 32.3 % of BRCA+ women were obese at the time of their breast cancer diagnosis whereas 17.7 % of BRCA- women were obese at the time of diagnosis (p = 0.09). Obesity status did not affect age at diagnosis in BRCA+ or BRCA- women (p = 0.3 and 0.4 respectively, n.s.). BRCA+ patients were more likely to have higher nuclear grade, ER/PR/Her2Neu negative (“triple negative”) tumors compared to BRCA- patients (ps < 0.01). Tumor pathology did not differ between obese women and non-obese women regardless of mutation status.
 >Discussion:
 >There was a trend for a larger proportion of BRCA+ women to be obese at diagnosis compared to BRCA- women. However, further research with a larger sample population should be conducted to determine the validity of this finding. In addition, these results provide further support for previous research which suggests that tumor pathology differs in BRCA+ and BRCA- cancers.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA