Format

Send to

Choose Destination
Breast Cancer Res Treat. 2016 Jul;158(2):307-21. doi: 10.1007/s10549-016-3883-z. Epub 2016 Jul 1.

Effects of TP53 and PIK3CA mutations in early breast cancer: a matter of co-mutation and tumor-infiltrating lymphocytes.

Author information

1
Department of Pathology, School of Health Sciences, School of Medicine, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. vkotoula@auth.gr.
2
Faculty of Medicine, Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. vkotoula@auth.gr.
3
Department of Medical Oncology, Papageorgiou Hospital, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
4
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
5
Department of Biostatistics, Health Data Specialists Ltd, Athens, Greece.
6
Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
7
The University of New South Wales, Kensington, NSW, Australia.
8
First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
9
Faculty of Medicine, Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
10
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
11
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece.
12
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece.
13
Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.
14
Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
15
Oncology Unit, Hippokration Hospital, Athens, Greece.
16
Second Department of Prop. Surgery, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
17
Breast Unit, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
18
Department of Medical Oncology, University Hospital of Larissa, University of Thessaly School of Medicine, Larissa, Greece.
19
Aristotle University of Thessaloniki, Thessaloniki, Greece.

Abstract

The purpose of this study is to investigate whether the outcome of breast cancer (BC) patients treated with adjuvant chemotherapy is affected by co-mutated TP53 and PIK3CA according to stromal tumor-infiltrating lymphocytes (TILs). Paraffin tumors of all clinical subtypes from 1661 patients with operable breast cancer who were treated within 4 adjuvant trials with anthracycline-taxanes chemotherapy were informative for TP53 and PIK3CA mutation status (semiconductor sequencing genotyping) and for stromal TILs density. Disease-free survival (DFS) was examined. TP53 mutations were associated with higher (p < 0.001) and PIK3CA with lower (p = 0.004) TILs in an ER /PgR-specific manner (p < 0.001). Mutations did not affect the favorable DFS of patients with lymphocyte-predominant (LP) BC. Within non-LPBC, PIK3CA-only mutations conferred best, while TP53-PIK3CA co-mutations (6 % of all tumors) conferred worst DFS (HR 0.59; 95 % CI 0.44-0.79; p = 0.001 for PIK3CA-only). TP53-only mutations were unfavorable in patients with lower TILs, while patients with lower TILs performed worse if their tumors carried TP53-only mutations (interaction p = 0.046). Multivariate analysis revealed favorable PIK3CA-only mutations in non-LPBC (HR 0.64; 95 % CI 0.47-0.88; p = 0.007), and unfavorable TP53 mutations in ER/PgRpos/HER2neg (HR 1.55; 95 % CI 1.07-2.24; p = 0.021). Mutations did not interact with TILs in non-LP triple-negative and HER2-positive patients. TP53 and PIK3CA mutations appear to have diverse effects on the outcome of early BC patients, according to whether these genes are co-mutated or not, and for TP53 according to TILs density and ER/PgR-status. These findings need to be considered when evaluating the effect of these two most frequently mutated genes in the context of large clinical trials.

KEYWORDS:

Adjuvant; Co-mutation; P53 immunohistochemistry; PIK3CA; TP53; Tumor-infiltrating lymphocytes

PMID:
27369359
DOI:
10.1007/s10549-016-3883-z
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center