PIK3CA Mutation in the ShortHER Randomized Adjuvant Trial for Patients with Early HER2 + Breast Cancer: Association with Prognosis and Integration with PAM50 Subtype

We explored the prognostic effect of mutation in HER2 patients enrolled in the ShortHER trial. The ShortHER trial randomized 1,253 patients with HER2 breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. hotspot mutations in exon 9 and 20 were analyzed by pyrosequenc...

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Veröffentlicht in:Clinical cancer research 2020-11, Vol.26 (22), p.5843-5851
Hauptverfasser: Guarneri, Valentina, Dieci, Maria Vittoria, Bisagni, Giancarlo, Brandes, Alba A, Frassoldati, Antonio, Cavanna, Luigi, Musolino, Antonino, Giotta, Francesco, Rimanti, Anita, Garrone, Ornella, Bertone, Elena, Cagossi, Katia, Nanni, Oriana, Piacentini, Federico, Orvieto, Enrico, Griguolo, Gaia, Curtarello, Matteo, Urso, Loredana, Paré, Laia, Chic, Nuria, D'Amico, Roberto, Prat, Aleix, Conte, Pierfranco
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Sprache:eng
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Zusammenfassung:We explored the prognostic effect of mutation in HER2 patients enrolled in the ShortHER trial. The ShortHER trial randomized 1,253 patients with HER2 breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression of 60 genes, including PAM50 genes was measured using the nCounter platform. A mutation of the 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 mutated and 86.2% for wild-type tumors [HR, 0.84; 95% confidence interval (CI), 0.56-1.27; = 0.417]. mutation showed a favorable prognostic impact in the PAM50 HER2-enriched subtype ( = 232): 5-year DFS 91.8% versus 76.1% (log-rank = 0.049; HR, 0.46; 95% CI, 0.21-1.02). HER2-enriched/ mutated versus wild-type tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related genes (including and , a proliferation gene involved in immune processes). High TILs as well as the upregulation of and were associated with a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68-0.99; = 0.039 for 10% TILs increment; HR, 0.81; 95% CI, 0.65-0.99; = 0.049 for expression; HR, 0.72; 95% CI, 0.53-0.99; = 0.042 for expression). mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with mutated tumors showed better DFS versus wild-type, which may be partly explained by upregulation of immune-related genes.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-20-1731