Breast cancer phenotype in women with TP53 germline mutations: A Li-Fraumeni syndrome consortium effort

Serena Masciari, Deborah A. Dillon, Michelle Rath, Mark Robson, Jeffrey N. Weitzel, Judith Balmana, Stephen B. Gruber, James M. Ford, David Euhus, Alexandra Lebensohn, Melinda Telli, Stephen M. Pochebit, Georgios Lypas, Judy E. Garber

Research output: Contribution to journalReview articlepeer-review

Abstract

Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohisto-chemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopath-ologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22-46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.

Original languageEnglish (US)
Pages (from-to)1125-1130
Number of pages6
JournalBreast Cancer Research and Treatment
Volume133
Issue number3
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • Breast Cancer
  • HER2
  • Hormone receptors
  • Li-Fraumeni syndrome
  • TP53 mutations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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