[247] Breast Cancer Subtypes and Epigenetic Characterization of in Women from Senegal, West Africa

Mara Rendi, Kimberly H Allison, Joshua Stern, Stephen Hawes, Qinghua Feng, Nancy Kiviat. University of Washington, Seattle

Background: We have previously described the frequency of pre/postmenopausal breast cancer as well as risk factors in a large cohort of women from Senegal, West Africa. In this study, our aims were to further characterize these cancers and to determine the histology, immunohistochemical profile, and methylation status of pre- and postmenopausal breast CA in West Africans.
Design: As previously reported, 522 consecutive women presenting to the Dakar Tumor Institute, Senegal, West Africa with a breast mass were enrolled and underwent a physical examination and medical history. Needle core biopsy of the mass was performed with subsequent histologic and immunohistochemical analysis with HER2 gene amplification status in equivocal cases. Immunohistochemical results were used as a surrogate to determine the breast cancer subtypes. Additionally, the epigenetic profile of these tumors was assessed by examining the methylation status of 32 genes known to be involved in breast and other epithelial cancers.
Results: Of the 522 women enrolled, the presence of cancer was confirmed in 197, 57% of which were premenopausal, 43%, postmenopausal. 96% of cases were invasive ductal carcinoma, with cases of invasive lobular carcinoma (2%) and mixed ductal and lobular features (2%) comprising the remainder. 75% of the cancers were Grade 3, 21% were Grade 2, and 4% were Grade 1. The IHC status is as follows:

Immunohistochemical Characterization of Senegalese Breast Cancer
 ER+/PR+/HER2-ER-/PR-/HER+TN (% of TN cases also CK 5/6 +)
Premenopausal40%19%41% (53% CK 5/6+)
Postmenopausal42%13%45% (47% CK 5/6+)
Total of all cases43%15%42% (67% CK 5/6+)
TN = Triple Negative

Of the 32 genes evaluated for methylation status, 5 genes, GSTP1, RASSF1, APC, HS3ST2, and SCGB3a1 were found to be hypermethylated in cancer compared with controls. Interestingly, these genes were only hypermethylated in the cancers that were positive for ER, PR, and/or Her2/neu expression whereas the triple negative cancers were found to be hypomethylated compared with controls.
Conclusions: Breast CA, in this population, was most commonly high grade, invasive ductal carcinoma with a high percentage of triple negative, CK 5/6+ cancers in both premenopausal and postmenopausal women. 5 genes were significantly hypermethylated in cancers that expressed ER, PR, and/or HER2 but interestingly were found to be hypomethylated in the triple negative cancers compared with controls. These data have important implications for the understanding of the molecular basis of both premenopausal and postmenopausal breast CA in West African and potentially African American women.
Category: Breast

Monday, March 19, 2012 1:00 PM

Poster Session II # 45, Monday Afternoon

 

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