Naslov
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
(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)

Autori
Ramić, Snježana ; Paić, Frane ; Smajlbegović, Velda ; Perić Balja, Melita ; Hiršl, Lea ; Marton, Ingrid ; Knežević, Fabijan

Izvornik
Croatian medical journal (0353-9504) 63 (2022), 2; 126-140

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
pHER2Y1248 predicts sensitivity to trastuzumab and a better five-year DFS regardless of any other prognostic parameter. In HER2-positive BC patients. Non-phosphorylated HER2Y1248 is a strong predictor of trastuzumab resistance and a poor DFS

Sažetak
Aim: To determine the predictive value of phosphorylated human epidermal growth factor receptor 2 (pHER2Y1248) status in breast cancer (BC) patients undergoing trastuzumab-based adjuvant therapy. Methods: Immunohistochemical status of pHER2Y1248, EGFR/HER1, HER3, and HER4 was determined in 124 consecutive HER2-positive BC patients (median age [range]=57 years [49.0- 64.0]) treated at the University Hospital for Tumors, Zagreb, between 2008 and 2011. The median follow-up 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, respectively. 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 histological 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 status (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 prognostic parameter. In HER2- positive BC patients. Non-phosphorylated HER2Y1248 is a strong predictor of trastuzumab resistance and a poor DFS.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA