Fountzilas, George and Giannoulatou, Eleni and Alexopoulou, Zoi and Zagouri, Flora and Timotheadou, Eleni and Papadopoulou, Kyriaki and Lakis, Sotiris and Bobos, Mattheos and Poulios, Christos and Sotiropoulou, Maria and Lyberopoulou, Aggeliki and Gogas, Helen and Pentheroudakis, George and Pectasides, Dimitrios and Koutras, Angelos and Christodoulou, Christos and Papandreou, Christos and Samantas, Epaminontas and Papakostas, Pavlos and Kosmidis, Paris and Bafaloukos, Dimitrios and Karanikiotis, Charisios and Dimopoulos, Meletios-Athanassios and Kotoula, Vassiliki (2016) TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting. Oncotarget, 7 (22). pp.32731-32753. ISSN 1949-2553 (OA)
Preview |
Text
Fountzilas 2016 TP53 mutations _Oncotarget OA.pdf Download (4MB) | Preview |
Abstract
BACKGROUND
We investigated the impact of PIK3CA and TP53 mutations and p53 protein status on the outcome of patients who had been treated with adjuvant anthracycline-taxane chemotherapy within clinical trials in the pre- and post-trastuzumab era.
RESULTS
TP53 and PIK3CA mutations were found in 380 (21.5%) and 458 (25.9%) cases, respectively, including 104 (5.9%) co-mutated tumors; p53 immunopositivity was observed in 848 tumors (53.5%). TP53 mutations (p < 0.001) and p53 protein positivity (p = 0.001) were more frequent in HER2-positive and triple negative (TNBC) tumors, while PIK3CA mutations were more frequent in Luminal A/B tumors (p < 0.001). TP53 mutation status and p53 protein expression but not PIK3CA mutation status interacted with trastuzumab treatment for disease-free survival; patients with tumors bearing TP53 mutations or immunopositive for p53 protein fared better when treated with trastuzumab, while among patients treated with trastuzumab those with the above characteristics fared best (interaction p = 0.017 for mutations; p = 0.015 for IHC). Upon multivariate analysis the above interactions remained significant in HER2-positive patients; in the entire cohort, TP53 mutations were unfavorable in patients with Luminal A/B (p = 0.003) and TNBC (p = 0.025); p53 immunopositivity was strongly favorable in patients treated with trastuzumab (p = 0.009).
MATERIALS AND METHODS
TP53 and PIK3CA mutation status was examined in 1766 paraffin tumor DNA samples with informative semiconductor sequencing results. Among these, 1585 cases were also informative for p53 protein status assessed by immunohistochemistry (IHC; 10% positivity cut-off).
CONCLUSIONS
TP53 mutations confer unfavorable prognosis in patients with Luminal A/B and TNBC tumors, while p53 immunopositivity may predict for trastuzumab benefit in the adjuvant setting.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 01 May 2016 23:35 |
| Last Modified: | 04 Jan 2017 00:27 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/430 |
Actions (login required)
 |
View Item |