title: Type of TP53 mutation and ERBB2 amplification affects survival in node-negative breast cancer.
abstract: Alterations of TP53 and ERBB2 have been shown to play important roles in the prognosis of breast cancer. The primary objective of this study is to characterize TP53 mutation types in node negative breast cancer and investigate their prognostic value, alone and in combination with ERBB2 amplification status. TP53 mutational status (exons 2-10) and ERBB2 amplification status were determined in tumor specimens from a prospective cohort of 543 women with node-negative breast cancer. During a median follow-up of 120 months, there were 111 disease recurrences, and 81 disease-related deaths (3 with cancer; 78 from cancer). Of 543 women, 133 (24.5%) carried mutations in exons 4-9 of the TP53 gene. Seventy-one (53.4%) of these mutations were missense; whereas 62 (46.6%) were protein-truncating mutations. Women whose tumors had missense TP53 mutations were found to be at significantly higher risk of recurrence and death compared to those with wild type TP53, and they also tended to have worse prognosis compared to those with truncating mutations. Those with short truncated proteins tended to have good prognosis compared to those with long truncated proteins, but the risk of recurrence and death did not differ between those whose tumors exhibited conserved versus non-conserved mutations. Missense mutations, in combination with ERBB2 amplification, were observed in 4.6% of the tumors and dramatically affected the disease-specific survival (DSS) and disease-free survival (DFS) of the breast cancer patients. Our study suggests that the type of TP53 mutation, especially missense mutation, is a strong prognostic indicator for DFS and DSS in node-negative breast cancer, particularly in combination with ERBB2 amplification.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray St., Room: 6-303-O, Toronto, ON, Canada, M5T 3L9. ozcelik@mshri.on.ca
authors.forename: Hilmi
authors.initials: H
authors.lastname: Ozcelik
authors.forename: Dushanthi
authors.initials: D
authors.lastname: Pinnaduwage
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D009154:Mutation / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C508053:ERBB2 protein, human