PIK3CA Mutation in the ShortHER Randomized Adjuvant Trial for Patients with Early HER2+ Breast Cancer: Association with Prognosis and Integration with PAM50 Subtype.
Clin Cancer Res
; 26(22): 5843-5851, 2020 11 15.
Article
in En
| MEDLINE
| ID: mdl-32843527
ABSTRACT
PURPOSE:
We explored the prognostic effect of PIK3CA mutation in HER2+ patients enrolled in the ShortHER trial. PATIENTS ANDMETHODS:
The ShortHER trial randomized 1,253 patients with HER2+ breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. PIK3CA hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression of 60 genes, including PAM50 genes was measured using the nCounter platform.RESULTS:
A mutation of the PIK3CA gene was detected in 21.7% of the 803 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6% for PIK3CA mutated and 86.2% for PIK3CA wild-type tumors [HR, 0.84; 95% confidence interval (CI), 0.56-1.27; P = 0.417]. PIK3CA mutation showed a favorable prognostic impact in the PAM50 HER2-enriched subtype (n = 232) 5-year DFS 91.8% versus 76.1% (log-rank P = 0.049; HR, 0.46; 95% CI, 0.21-1.02). HER2-enriched/PIK3CA mutated versus wild-type tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related genes (including CD8A, CD274, PDCD1, and MYBL2, a proliferation gene involved in immune processes). High TILs as well as the upregulation of PDCD1 and MYBL2 were associated with a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68-0.99; P = 0.039 for 10% TILs increment; HR, 0.81; 95% CI, 0.65-0.99; P = 0.049 for PDCD1 expression; HR, 0.72; 95% CI, 0.53-0.99; P = 0.042 for MYBL2 expression).CONCLUSIONS:
PIK3CA mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with PIK3CA mutated tumors showed better DFS versus PIK3CA wild-type, which may be partly explained by upregulation of immune-related genes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
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Receptor, ErbB-2
/
Class I Phosphatidylinositol 3-Kinases
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Trastuzumab
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Female
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Humans
/
Middle aged
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2020
Document type:
Article
Affiliation country:
Italy