Messaggi chiave
- Gli autori del presente studio hanno esaminato l’espressione di HER2 in campioni pre- e post-trattamento di pazienti consecutive con carcinoma mammario in stadio precoce sottoposte a terapia neoadiuvante (NAT) e successiva chirurgia nel periodo gennaio 2016 – agosto 2022. L’outcome primario di interesse era l’evoluzione dell’espressione di HER2 nei campioni pre- e post-NAT delle pazienti con malattia residua all’intervento chirurgico.
- L’espressione di HER2 si è modificata in un totale di 319 su 1080 (~30%) pazienti con malattia residua alla chirurgia, con una distribuzione sostanzialmente equivalente tra diminuzione e aumento dell’espressione. La probabilità di osservare un’evoluzione nell’espressione di HER2 è risultata significativamente maggiore nelle pazienti con malattia HER2-0 o HER2-low rispetto a HER2+.
- La presenza di variazioni post-NAT nell’espressione di HER2 è stata prognostica nelle pazienti con tumori HER2+ alla diagnosi – con una sopravvivenza libera da recidiva a 3 anni del 71,6% in presenza di un’evoluzione a HER2 rispetto all’89,6% in assenza di variazioni (p = 0,006), ma non in quelle con malattia HER2-.
Abstract
Introduction
- We have previously found that HER2 expression is dynamic, and can change from the primary breast tumor to matched recurrences. With this work, we aimed to assess the dynamics of HER2 during neoadjuvant treatment (NAT).
Methods
- We reviewed HER2 expression in pre- and post-treatment samples from consecutive patients with early-stage breast cancer that received NAT and underwent surgery at Dana-Farber Brigham Cancer Center between 01/2016-08/2022.
- The primary outcome was evolution of HER2 expression from pre- to post-NAT specimens in patients with residual disease.
Results
- Among 1613 patients receiving NAT, 1080 had residual disease at surgery. A total of 319 patients (29.5%) experienced a change in HER2 expression (HER2 0 vs. HER2-low vs. HER2-positive) from the pre-treatment sample to residual disease, with roughly equal distribution between decreased (50.5%) and increased HER2 expression (49.5%). Similar rates of change in HER2 expression were observed with anthracycline-based (31.8%) or taxane/platinum-based regimens (32.4%).
- Patients with HER2-0 or HER2-low tumors at diagnosis were likelier to experience a change in HER2 expression post-NAT compared to HER2-positive (32.3% vs. 21.3%, p <0.001). Changes in HER2 expression post-NAT were prognostic among patients with HER2-positive tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 71.6% vs. 89.6%, p = 0.006) but not among those with HER2-negative tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 79.3% vs. 81.1%, p = 0.31).
Conclusions
- Nearly 30% of patients with early-stage breast cancer showed a change in HER2 expression after NAT. Changes in HER2 expression post-NAT were only prognostic in the setting of HER2-positive tumors becoming HER2-negative at surgery.