TY - JOUR
T1 - PIK3CA Mutation in the ShortHER Randomized Adjuvant Trial for Patients with Early HER2(+) Breast Cancer: Association with Prognosis and Integration with PAM50 Subtype
AU - Guarneri, Valentina
AU - Dieci, Maria Vittoria
AU - Bisagni, Giancarlo
AU - Brandes, Alba A.
AU - Frassoldati, Antonio
AU - Cavanna, Luigi
AU - Musolino, Antonino
AU - Giotta, Francesco
AU - Rimanti, Anita
AU - Garrone, Ornella
AU - Bertone, Elena
AU - Cagossi, Katia
AU - Nanni, Oriana
AU - Piacentini, Federico
AU - Orvieto, Enrico
AU - Griguolo, Gaia
AU - Curtarello, Matteo
AU - Urso, Loredana
AU - Pare, Laia
AU - Chic, Nuria
AU - D'Amico, Roberto
AU - Prat, Aleix
AU - Conte, Pierfranco
PY - 2020/11/15
Y1 - 2020/11/15
N2 - Purpose: We explored the prognostic effect of PIK3CA mutation in HER2(+) patients enrolled in the ShortHER trial. Patients and Methods: 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 21.703 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6CA mutated and 86.2CA wild-type tumors [HR, 0.84; 95CI), 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 91.86.1log-rank P = 0.049; HR, 0.46; 95 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 0.68-0.99; P = 0.039 for 10 HR, 0.81; 95 0.65-0.99; P = 0.049 for PDCD1 expression; HR, 0.72; 95 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.
AB - Purpose: We explored the prognostic effect of PIK3CA mutation in HER2(+) patients enrolled in the ShortHER trial. Patients and Methods: 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 21.703 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6CA mutated and 86.2CA wild-type tumors [HR, 0.84; 95CI), 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 91.86.1log-rank P = 0.049; HR, 0.46; 95 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 0.68-0.99; P = 0.039 for 10 HR, 0.81; 95 0.65-0.99; P = 0.049 for PDCD1 expression; HR, 0.72; 95 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.
U2 - 10.1158/1078-0432.CCR-20-1731
DO - 10.1158/1078-0432.CCR-20-1731
M3 - Article
VL - 26
SP - 5843
EP - 5851
JO - Clin. Cancer Res.
JF - Clin. Cancer Res.
SN - 1078-0432
IS - 22
ER -