e12592 Background: Achieving pCR following neoadjuvant chemo and anti-HER2 therapy is associated with a significantly better survival in HER2+ BC. There is currently a lack of a robust biomarker to predict pCR in HER2+ BC. Using EFTUD2 as chromosome 17 reference probe, circulating HER2/EFTUD2 plasma DNA copy number ratio (H-ratio) detected by droplet digital PCR (ddPCR) was shown to have high concordance with the tumor HER2 status. We aim to evaluate whether the change in H-ratio is associated with response to neoadjuvant dual anti-HER2 therapy. Methods: We prospectively recruited patients with HER2+ BC who received neoadjuvant taxane, trastuzumab and pertuzumab followed by radical surgery from May 2019 to April 2022. Serial plasma samples (n = 49) were collected at pre-treatment (Tpre), at 4th cycle (Tmid) and at completion of neoadjuvant treatment (Tpost). H-ratio was determined in each plasma sample using droplet ddPCR (QX200 ddPCR system, Bio-rad). H-ratio responders were defined as patients having a declining Tpost H-ratio, whereas patients having a rising or persistent Tpost H-ratio were defined as H-ratio non-responders. The relationship between pCR, H-ratio and various clinicopathological characteristics were evaluated by Spearman’s correlation, Fisher’s exact test and Wilcoxon signed-rank test. Results: Eighteen clinical stage II or III HER2+ BC patients with a median age of 56 years old (range 33 - 71) were included. The median H-ratio at Tpre, Tmid and Tpost were 1.27, 1.12 and 1.10, respectively. Higher Tpre H-ratio was significantly associated with larger tumor size (p = 0.004) and higher tumor grade (G1-2 vs G3; median H-ratio 1.15 vs 1.78; p = 0.024). Six patients (33.3%) were H-ratio responders. Ten (55.6%) of 18 patients achieved pCR after completion of neoadjuvant treatment. The pCR rate in H-ratio responders was significantly higher than the H-ratio non-responders (100% vs. 36.4%; p = 0.017). In predicting pCR, H-ratio response outperformed hormonal receptor (HR) negativity (HR- vs HR+; 72.7% vs 28.6%; p = 0.088) or high tumor grade (G1-2 vs G3; 66.7% vs 33.3%; p = 0.201). There was no association between pCR and Tpre/Tmid/Tpost H-ratio. With a median follow up of 22.8 months (range 8.2 - 41.8), there were no relapse or death. Conclusions: A high pre-treatment plasma circulating HER2/EFTUD2 ratio is associated with large tumor size and high tumor grade in HER2+ BC. The decline of HER2/EFTUD2 ratio after neoadjuvant dual anti-HER2 therapy predicts pCR, and may serve as a potential biomarker for treatment de-escalation.
1043 Background: Dual anti-HER2 antibodies pertuzumab (P) and trastuzumab (T) in combination with taxane (D), followed by PT maintenance, is the standard first line treatment for HER2 positive advanced breast cancer (HER2+ ABC). Treatment associated cardiotoxicity necessitates regular cardiac function surveillance, which is a burden particularly for treatment long-responders. Data for cardiac safety of prolonged P+T exposure is scarce. We investigate the real-world impact on cardiac function in long-responders to treatment with dual anti-HER2 antibodies. Methods: We identified consecutive patients with HER2+ ABC who received the CLEOPATRA regimen (PT-D) between Jan 2014 and Dec 2020 from an institutional cancer registry. All patients had pre-treatment multiple-gated acquisition (MUGA) scan or echocardiogram, and subsequently at 3-monthly intervals until end of treatment to monitor left ventricular ejection fraction (LVEF). Patients on treatment for ≥36 months were considered long-responders. The Wilcoxon signed-rank test was used to assess any significant difference in LVEF at various landmark time-points in comparison to their pretreatment baseline. Results: 101 women with HER2+ ABC were eligible for analysis. Median age at treatment was 62 (IQR, 56.0-69.0). The median duration of treatment was 17.3 months (IQR, 9.0-31.3). 22.8% of patients were long-responders, who received a median of 67 cycles of treatment (IQR, 58-88). Compared to baseline, median LVEF was significantly decreased at 6m (median, 66% vs 69%, p=0.02), however there were no significant differences for any of the subsequent time-points up to 84 m. All of the larger LVEF drop (≥10% from baseline) occurred by the first 24 months, representing 4.7% of the overall measurements. Risk factors present for patients experienced treatment suspension (n=3) included previous exposures to anthracycline and left sided radiotherapy. Conclusions: In patients with HER2+ ABC who were long-responders to first-line PT-D, prolonged exposure to dual anti-HER2 antibodies was not associated with significant cardiotoxicity. It is safe to de-escalate the cardiac surveillance for this population. [Table: see text]
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