RT Journal Article
SR Electronic
T1 PI3K/PTEN/mTOR pathway dynamic tracking and prognostic value in HR+/HER2− BC patients with residual disease after neoadjuvant chemotherapy: a cohort study
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 690
OP 696
DO 10.1136/jcp-2023-208856
VO 77
IS 10
A1 Miglietta, Federica
A1 Carraro, Valentina
A1 Amato, Ottavia
A1 Griguolo, Gaia
A1 Bottosso, Michele
A1 Munari, Giada
A1 Zarrilli, Giovanni
A1 Lo Mele, Marcello
A1 Barbieri, Caterina
A1 Dei Tos, Angelo Paolo
A1 Guarneri, Valentina
A1 Dieci, Maria Vittoria
A1 Fassan, Matteo
YR 2024
UL http://jcp.bmj.com/content/77/10/690.abstract
AB Aims Hormone receptor-positive (HR)+/HER2− breast cancer (BC) is highly heterogeneous, with PI3K/PTEN/mTOR pathway alterations emerging as possible players within this complexity. We longitudinally tracked PI3K/PTEN/mTOR pathway dynamics from baseline biopsy to residual disease (RD)—and to metastases in case of relapse—in HR+/HER2− BC patients receiving neoadjuvant chemotherapy (NACT).Methods HR+/HER2− BC patients with RD after NACT were identified. We assessed PIK3CA mutational, Pten-loss and phosphorylation levels of mTOR and its substrates (p70S6K and 4EBP1) on baseline biopsies and matched RD samples; in case of disease relapse, we also assessed PIK3CA mutational status on metastatic samples. Recurrence-free survival (RFS) was adopted as endpoint.Results 92 patient were included. The conversion rate of PIK3CA mutational status was 12.8%; 1 patient acquired PIK3CA mutation at relapse; the rate of Pten conversion was 33.3%; mTOR phosphorylation levels significantly increased from baseline biopsy to RD, while its substrates significantly decreased. Baseline phosphorylated-mTOR significantly predicted poorer RFS in patients with PIK3CA wild-type status; baseline phosphorylated-70S6K was positively associated with RFS.Conclusions We observed that PI3K/PTEN/mTOR pathway is highly dynamic under NACT exposure and the assessment of PIK3CA mutations may capture only a small fraction of such complexity. In this context, mTOR activation trough alternative pathways with respect to PIK3CA signalling may have a crucial role in shaping the molecular landscape of HR+/HER2− BC with RD after NACT. It is imperative to further elucidate the role of PIK3CA and mTOR-dependent pathways in shaping chemoresistance and endocrine resistance in high-risk HR+/HER2− early/locally advanced BC patients.Data are available on reasonable request. The datasets that support the findings of this study are not publicly available in order to protect patient privacy. The data will be available on reasonable request from the corresponding author: FM (federica.miglietta@unipd.it)