PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: Pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab

S. Loibl*, I. Majewski, V. Guarneri, V. Nekljudova, E. Holmes, Emilio Bria, C. Denkert, C. Schem, C. Sotiriou, S. Loi, M. Untch, P. Conte, R. Bernards, M. Piccart, G. von Minckwitz, J. Baselga

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo

88 Citazioni (Scopus)

Abstract

Background: The predictive value of PIK3CA mutations in HER2 positive (HER2+) breast cancer treated with neoadjuvant anti-HER2 and chemotherapy has been reported, but the power for subgroup analyses was lacking. Patients and methods: We combined individual patient data from five clinical trials evaluating PIK3CA mutations and associations with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Patients received either trastuzumab (T), lapatinib (L) or the combination T/L in addition to a taxane-based chemotherapy. PIK3CA was genotyped in tumour biopsies taken before therapy. Results: A total of 967 patients were included in this analysis; the median follow-up is 47 months. Overall, the pCR rate was significantly lower in the PIK3CA mutant compared with the wild-type group (16.2% versus 29.6%; P < 0.001). Within the hormone-receptor positive (HR+) subgroup, the PIK3CA mutant group had a pCR rate of only 7.6% compared with 24.2% in the wild-type group (P < 0.001). In contrast, in the HER2+/HR- group, there was no difference in pCR (27.2% versus 36.4%; P = 0.125) according to PIK3CA mutation status (interaction test P = 0.036). According to treatment arm, the pCR rate for mutant versus wild-type was 20.3% versus 27.1% for T (P = 0.343), 11.3% versus 16.9% for L (P = 0.369) and 16.7% versus 39.1% for T/L (P < 0.001). In the HR+ T/L group, the pCR rate was 5.5% versus 33.9% (interaction between HR and PIK3CA genotype P = 0.008). DFS and OS were not significantly different by mutation status, though the incidence rate of events was low. However, HR+/PIK3CA mutant patients seemed to have significantly worse DFS {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.00-2.45], P = 0.050; Pinteraction = 0.021}. T/L tended to improve DFS compared with T in the wild-type cohort, especially in the HR- group [HR 0.72, 95% CI (0.41-1.25), P = 0.242]. Conclusion: Overall PIK3CA mutant/HER2+ tumours had significantly lower pCR rates compared with wild-type tumours, however mainly confined to the HR+/PIK3CA mutant population. No definite conclusions can be drawn regarding survival.
Lingua originaleInglese
pagine (da-a)1519-1525
Numero di pagine7
RivistaAnnals of Oncology
Volume27
Numero di pubblicazione8
DOI
Stato di pubblicazionePubblicato - 2016

All Science Journal Classification (ASJC) codes

  • Ematologia
  • Oncologia

Keywords

  • Adjuvant
  • Adult
  • Aged
  • Antibodies
  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers
  • Breast Neoplasms
  • Chemotherapy
  • Class I Phosphatidylinositol 3-Kinases
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Double anti-HER2 treatment
  • ErbB-2
  • Female
  • Genotype
  • HER2+ breast cancer
  • Humanized
  • Humans
  • Lapatinib
  • Middle Aged
  • Monoclonal
  • Neoadjuvant
  • PIK3CA
  • Pathological complete response
  • Quinazolines
  • Receptor
  • Survival
  • Trastuzumab
  • Tumor

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