| Title |
Effects of TP53 and PIK3CA mutations in early breast cancer: a matter of co-mutation and tumor-infiltrating lymphocytes
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, July 2016
|
| DOI | 10.1007/s10549-016-3883-z |
| Pubmed ID | |
| Authors |
Vassiliki Kotoula, Vasilios Karavasilis, Flora Zagouri, George Kouvatseas, Eleni Giannoulatou, Helen Gogas, Sotiris Lakis, George Pentheroudakis, Mattheos Bobos, Kyriaki Papadopoulou, Eleftheria Tsolaki, Dimitrios Pectasides, Georgios Lazaridis, Angelos Koutras, Gerasimos Aravantinos, Christos Christodoulou, Pavlos Papakostas, Christos Markopoulos, George Zografos, Christos Papandreou, George Fountzilas |
| 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 47 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 13% |
| Student > Ph. D. Student | 5 | 11% |
| Student > Master | 5 | 11% |
| Professor > Associate Professor | 4 | 9% |
| Other | 4 | 9% |
| Other | 9 | 19% |
| Unknown | 14 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 18 | 38% |
| Biochemistry, Genetics and Molecular Biology | 6 | 13% |
| Agricultural and Biological Sciences | 4 | 9% |
| Nursing and Health Professions | 2 | 4% |
| Economics, Econometrics and Finance | 1 | 2% |
| Other | 3 | 6% |
| Unknown | 13 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 July 2016.
All research outputs
#17,810,867
of 22,880,230 outputs
Outputs from Breast Cancer Research and Treatment
#3,577
of 4,659 outputs
Outputs of similar age
#252,879
of 351,902 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#55
of 99 outputs
Altmetric has tracked 22,880,230 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,659 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 351,902 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 99 others from the same source and published within six weeks on either side of this one. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.