Therapeutic advances in medical oncology · 2026
Dynamics of HER2 status following neoadjuvant systemic therapy in breast cancer: a large single-center cohort analysis.
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Pogoda Katarzyna, Czopowicz Magdalena, Bak Agata, Olszewski Wojciech, Czopowicz Michal, Durzynska Monika, Najmrocka Dorota, Halasa Paulina, Borowiec Anna, Nowecki Zbigniew, Niwinska Anna
Аннотация
BACKGROUND: Receptor conversion, including changes in human epidermal growth factor receptor 2 (HER2) expression, has been reported after neoadjuvant therapy (NAT), but determinants of HER2 changes between baseline biopsy and residual disease remain incompletely understood.
OBJECTIVE: To evaluate the rate of HER2 status conversion after NAT and to identify factors associated with these changes in the context of contemporary treatment standards.
DESIGN: Retrospective analysis of patients with breast cancer (BC) treated with NAT followed by surgery between January 2019 and June 2024.
METHODS: BC was classified as HER2-0, HER2-low, or HER2-positive. HER2 expression before and after NAT was compared. Probabilities of HER2 subtype conversion were estimated, and univariable and multivariable analyses were performed to assess clinicopathological factors associated with HER2 status changes.
RESULTS: A total of 736 patients were included in the analysis, with HER2 status conversion observed in 34.2% (252/736) patients. The shift in HER2 expression occurred in 38.5% (94/244) of HER2-0, 27.9% (95/340) of HER2-low, and 41.4% (63/152) of HER2-positive tumors. A decrease in HER2 status was significantly more common than an increase (29.7% vs 18.2%; p < 0.001). The acquisition of HER2 positivity from initially HER2-0/low tumors was rare, occurring in only 19/584 (3.3%) cases. Downregulation of HER2 status from HER2-positive to HER2-0/low was more frequently observed in tumors initially classified as HER2 2+ with a positive fluorescence in situ hybridization (FISH) result compared to HER2 3+ tumors (adjusted odds ratio (ORadj) = 2.43, 95% confidence interval (CI): 1.18-5.01; p = 0.017). Similarly, the conversion from HER2-low to HER2-0 was observed more often in tumors initially classified as HER2 1+ compared to HER2 2+ with a negative FISH result (ORadj = 3.14; 95% CI: 1.20-8.22; p = 0.009). Conversely, the acquisition of HER2 positivity was significantly associated with high-grade (G3) tumors (ORadj = 5.50; 95% CI: 2.12-14.3; p < 0.001) and estrogen receptor expression >10% (ORadj = 8.61; 95% CI: 1.09-68.1; p = 0.041).
CONCLUSION: HER2 status conversion affects about one-third of BCs after NAT, most commonly as downregulation, supporting HER2 reassessment in residual disease to guide post-NAT treatment decisions.
OBJECTIVE: To evaluate the rate of HER2 status conversion after NAT and to identify factors associated with these changes in the context of contemporary treatment standards.
DESIGN: Retrospective analysis of patients with breast cancer (BC) treated with NAT followed by surgery between January 2019 and June 2024.
METHODS: BC was classified as HER2-0, HER2-low, or HER2-positive. HER2 expression before and after NAT was compared. Probabilities of HER2 subtype conversion were estimated, and univariable and multivariable analyses were performed to assess clinicopathological factors associated with HER2 status changes.
RESULTS: A total of 736 patients were included in the analysis, with HER2 status conversion observed in 34.2% (252/736) patients. The shift in HER2 expression occurred in 38.5% (94/244) of HER2-0, 27.9% (95/340) of HER2-low, and 41.4% (63/152) of HER2-positive tumors. A decrease in HER2 status was significantly more common than an increase (29.7% vs 18.2%; p < 0.001). The acquisition of HER2 positivity from initially HER2-0/low tumors was rare, occurring in only 19/584 (3.3%) cases. Downregulation of HER2 status from HER2-positive to HER2-0/low was more frequently observed in tumors initially classified as HER2 2+ with a positive fluorescence in situ hybridization (FISH) result compared to HER2 3+ tumors (adjusted odds ratio (ORadj) = 2.43, 95% confidence interval (CI): 1.18-5.01; p = 0.017). Similarly, the conversion from HER2-low to HER2-0 was observed more often in tumors initially classified as HER2 1+ compared to HER2 2+ with a negative FISH result (ORadj = 3.14; 95% CI: 1.20-8.22; p = 0.009). Conversely, the acquisition of HER2 positivity was significantly associated with high-grade (G3) tumors (ORadj = 5.50; 95% CI: 2.12-14.3; p < 0.001) and estrogen receptor expression >10% (ORadj = 8.61; 95% CI: 1.09-68.1; p = 0.041).
CONCLUSION: HER2 status conversion affects about one-third of BCs after NAT, most commonly as downregulation, supporting HER2 reassessment in residual disease to guide post-NAT treatment decisions.