Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2022.63.12 6
Non-phosphorylated Tyr-1248 form of human epidermal growth factor receptor 2 (HER2) predicts resistance to trastuzumab therapy and poor disease-free survival of HER2- positive breast cancer patients
Snježana Ramić
; Department of Oncological Pathology, University Hospital for Tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
Frane Paić
; Laboratory for Epigenetic and Molecular Medicine, Department of Medical Biology, University of Zagreb School of Medicine, Zagreb, Croatia
Velda Smajlbegović
; Oncology Clinic, Clinical Center of Sarajevo University, Sarajevo, Bosnia and Herzegovina
Melita Perić Balja
; Department of Oncological Pathology, University Hospital for Tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
Lea Hiršl
; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
Ingrid Marton
; Department of Pathology, Sveti Duh University Hospital, Zagreb, Croatia
Fabijan Knežević
; Department of Pathology, Sveti Duh University Hospital, Zagreb, Croatia
Sažetak
Aim To determine the predictive value of phosphorylat
-
ed human epidermal growth factor receptor 2 (pHER2Y1248)
status in breast cancer (BC) patients undergoing trastu
-
zumab-based adjuvant therapy.
Methods Immunohistochemical status of pHER2Y1248,
EGFR/HER1, HER3, and HER4 was determined in 124 consec
-
utive HER2-positive BC patients (median age [range]
=57
years [49.0-64.0]) treated at the University Hospital for Tu
-
mors, Zagreb, between 2008 and 2011. The median followup was 84 months (60.0-84.0). Prognostic factors of disease
free survival (DFS) rate were evaluated with Kaplan-Meier/
log-rank test and Cox regression analysis.
Results pHER2Y1248, HER1, HER3, and HER4 were expressed
in 66.1%, 9.7%, 70.2%, and 71.0% of patients, respective
-
ly. Disease progression (DP) was observed in 17.1% of
pHER2Y1248-positive and 47.6% of pHER2Y1248-negative BCs (P=0.001). Kaplan-Meier analysis showed a worse five-year
DFS in pHER2Y1248-negative patients who were older than
60 years (
P
<0.001) and had positive lymph node status
(
P
<0.001); tumor size >2.0 cm (
P
<0.001); higher histologi
-
cal grade (
P
<0.001); HER2E intrinsic subtype (
P
<0.001),
negative hormone receptors (
P
<0.001); negative HER1
status (
P
<0.001), positive HER3 (
P
=0.002); and/or positive
HER4 (
P
=0.002) status. The only negative prognostic factor
for five-year DFS in multivariate Cox regression analysis was
pHER2Y1248-negative (hazard ratio [HR] 3.6, 95% confidence
interval [CI] 1.8-7.2,
P
<0.001) and lymph node-positive sta
-
tus (HR 3.6, 95% CI 1.3-9.8,
P
=0.014).
Conclusion pHER2Y1248 predicts sensitivity to trastuzumab
and a better five-year DFS regardless of any other prognos
-
tic parameter. In HER2-positive BC patients. Non-phospho
-
rylated HER2Y1248 is a strong predictor of trastuzumab resis
-
tance and a poor DFS.
Ključne riječi
Hrčak ID:
279008
URI
Datum izdavanja:
21.4.2022.
Posjeta: 635 *