Histopathological features of breast cancers in women with germline TP53 mutations

Abstract

10031 Background: Breast cancers (BR) in women with germline BRCA1 mutations are usually high-grade ductal carcinomas; 90% are negative for estrogen receptor (ER), progesterone receptor (PR) and HER2. No characteristic phenotype has been found for BRCA2-associated tumors. For women with germline TP53 mutations (Li Fraumeni Syndrome), breast cancer is the most common tumor; the risk of BR is 49% by age 60, with significant risk before age 40. The histopathological profile of BR in women with germline TP53 mutations has not been characterized. Methods: We identified BR from 17 female TP53 mutation carriers from the LFS family registry at Dana Farber Cancer Institute on which at least ER and PR data were available. Information on histology, hormone receptor and HER2 status by immunohistochemistry (IHC) was collected from medical records. Histology was not centrally reviewed. Results: 14 invasive ductal carcinoma (IDC) and 4 DCIS were identified in 17 women (1 woman had both) (see Table). The median age at diagnosis of invasive BR was 30 years (range 24–48), for DCIS it was 37 years (range 22–40). Of the 14 IDC, 11 (79%) were high grade (G3), 10 (71%) were ER positive, 7 (50%) PR positive, 6 PR negative and 1 PR unknown. Among 9 tumors with available HER2 status, 6 (67%) were positive. Both ER+/PR+ and ER-/PR- DCIS were observed. Conclusions: In young women with TP53 germline mutations, BR are more likely to be high grade and ER positive with no other distinct pattern in contrast to BRCA1-associated tumors. Findings of DCIS alone suggest potential value for mammographic screening. Confirmation of these results in a larger series will be important. [Table: see text] No significant financial relationships to disclose.