Breast cancer phenotype in women with TP53 germ-line mutations: An LFS consortium effort.

Abstract

1519 Background: Breast cancer (BC) is the most common tumor in women with germ-line TP53 mutations with 49% risk by age 60, and significant risk before age 40. The histopathological profile of BC in TP53 carriers has recently been described in small cohorts showing a higher likelihood of HER2+ BC (Wilson et al. J Med Genet.Nov;47:771-774; Melhem-Bertrandt ARK et al. 2010 San Antonio Breast Cancer Symp; Poster Session 3). We expanded our original cohort of 17 women with BC and Li Fraumeni syndrome (LFS), in whom we had complete markers only in 9 cases (Masciari S et al. JCO, 2006 ASCO Annual Meeting Proc, abstr 10031), to characterize the histopathological features of BC in LFS. Methods: We identified 15 BC from germ-line TP53mutations carriers from the LFS registry at Dana-Farber Cancer Institute and 14 cases from collaborators in the LFS consortium. Information on histology, hormone receptor and HER2 status was collected from medical records. Central histology review is ongoing and complete data from the cohort will be available shortly, including 13 additional cases. Results: We identified 7 DCIS and 22 invasive ductal carcinoma (IDC) in 26 women, 1 with both and 2 with bilateral IDC. The median age at IDC was 31 years (range 22-46). 64% were high grade, 17 (77%) were ER+ and 16 (72%) were PR+. 68% of IDC and 71% of DCIS were HER2+. 45% of IDC were ER+/PR+/HER2+; other ER/PR/HER2 combinations were observed (Table). Conclusions: This is the largest collection of BC with characterized subtype reported in women with LFS. Most DCIS and IDC in LFS are hormone receptor positive; HER2+ frequency is also increased. These findings suggest that modern treatments may improve outcomes for women with LFS-associated BC. It is important to identify them to permit consideration of radiation issues and additional primary malignancies. Histopathologic characteristics of BC in LFS. N ER+ PR+ HER2+ ER+/PR+ ER-/PR- ER+/PR- HER2+ HER2- HER2+ HER2- HER2+ DCIS 7 4 3 5 1 2 3 0 1 IDC 22 17 16 15 10 6 4 1 1 Total 29 21 19 20 11 8 7 1 2