Abstract P2-05-05: Circulating HER2 extracellular domain (ECD) predicts a poor prognosis for metastatic breast cancer patients

Abstract

Background: Amplification or overexpression of HER2 has been shown to play an important role in approximately 30% of breast cancers and is strongly associated with increased recurrence and a worse prognosis. The HER2 extracellular domain (ECD) may be cleaved and shed from the surface of breast cancer cells and serum HER2 ECD levels can be detected by enzyme-linked immunosorbent assay (ELISA). In this study, we explored the relationship between circulating HER2 ECD and tissue HER2 status, then we also examined its predictive value in a cohort of metastatic breast cancer patients. Methods: Two hundred and seven metastatic breast cancer patients from March 2009 to July 2011 were involved in this prospective study at Zhejiang Cancer Hospital. The patients were identified histopathologically as having breast cancer by pathologists and staged mainly based on the pathology, the clinical manifestation, and the imaging findings of CT and MRI according to the classification system of the International Union Against Cancer. Serum HER2 ECD levels were measured by ELISA. Tissue HER2 was determined by IHC and FISH in tumor samples, respectively. Results: The level of serum HER2 ECD was at least more than 15 ng/ml in 31.4% (65/207) metastatic breast cancer patients, 39.1%(43/110) in HER2-positive patients and 23.4%(22/94) in HER2-negative cases, respectively, P = 0.017. We also found that high serum HER2 ECD levels (≥15 ng/ml) were significantly associated with elevated serum CEA (52.1% v 21.5%, OR 3.978, 95%CI 2.138–7.401, P = 0.000), CA125 (48.5% v 23.5%, OR 3.064, 95%CI 1.650–5.691, P = 0.000), CA153 (53.2% v 17.1%, OR 5.48, 95%CI 2.897–10.366, P = 0.000), LDH (53.3% v 23.1%, OR 3.798, 95%CI 2.011–7.173, P = 0.000) and AKP (51.2% v 26.5%, OR 2.911, 95%CI 1.442–5.879, P = 0.002), respectively. For the effect of HER2 ECD on the site of relapse, still there were statistically significant correlation between increased serum HER2 ECD levels and liver involvement (42.7% v 24.0%, OR 2.358, 95%CI 1.294–4.297, P = 0.005), brain metastasis (50.0% v 26.7%, OR 2.744, 95%CI 1.397–5.391, P = 0.003) and visceral involved (37.9% v 14.8%, OR 3.511, 95%CI 1.548–7.961, P = 0.002), respectively. While serum HER2 ECD levels were not related to age, BMI, tumor size, lymph node involvement and hormone receptors status, respectively (P>0.05). Conclusions: Monitoring the circulating levels of the HER2 ECD in patients with metastatic breast cancer provides a real-time assessment of tumor burden and indicates poor prognosis, and may provide important information for reassessment of HER2 in HER2-negative metastatic breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-05.

Exploring the concepts and practices of advanced breast cancer treatment: a narrative review

“…Till now, we have 4 editions which have been also recognized by international experts. These guidelines further improved the survival and the quality life of MBC patients both in China and all over the world (17)(18)(19) (20). We explored he relationship between circulating ECD and clinical pathological characteristics.…”

Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation

“…HER2 is overexpressed in ∼25% of all breast cancer cases and it is used to determine progression and prognosis . Based on this, Berstad et al .…”

“…39 Human epidermal growth factor receptor 2 HER2 is overexpressed in 25% of all breast cancer cases and it is used to determine progression and prognosis. 60,61 Based on this, Berstad et al in 2012 28 combined trastuzumab (HerceptinV R )-saporin and a chlorin photosensitiser to compare PDT versus PCI induced cell killing on either HER2 1 or HER2 2 breast cancer cells. 28 Light administration post exposure of cells to (HerceptinV R )-saporin in PCI was far superior in cell killing compared to PDT and the PCI light-before treatment.…”