J Cancer 2022; 13(3):744-751. doi:10.7150/jca.66567 This issue Cite

Research Paper

Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients

Suhong Xie1,2*, Yan Wang5,6*, Zhiyun Gong1,2*, Yuan Li2, Wentao Yang2, Guangyu Liu2, Jianwei Li2, Xin Hu2, Yanchun Wang1,2, Yin Tong1,2, Peng Yuan3, Yiran Si3, Yikun Kang3, Yong Mao4, Xiaowei Qi4, Yankui Liu4, Jiajia Ou5, Zhaoliang Li5, Xin Pan5, Zhaoqing Lv5, Kavanaugh Kaji6, Lin Guo1,2✉, Renquan Lu1,2✉

1. Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, P. R. China.
2. Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, P. R. China.
3. Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
4. Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, P. R. China.
5. Questgenomics, No.12 Mozhou East Rd, Nanjing, Jiangsu, P. R. China.
6. Gnomegen, 6440 Lusk Blvd, D207, San Diego, CA, 92121 United States.
*These authors contributed equally to this work.

Citation:
Xie S, Wang Y, Gong Z, Li Y, Yang W, Liu G, Li J, Hu X, Wang Y, Tong Y, Yuan P, Si Y, Kang Y, Mao Y, Qi X, Liu Y, Ou J, Li Z, Pan X, Lv Z, Kaji K, Guo L, Lu R. Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients. J Cancer 2022; 13(3):744-751. doi:10.7150/jca.66567. https://www.jcancer.org/v13p0744.htm
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Abstract

Graphic abstract

Two hundred twenty-four breast cancer patients with paired tissue and plasma samples were enrolled from 3 clinical centers to evaluate sensitivity and specificity of a digital PCR HER2 amplification assay. All patients were histologically confirmed diagnosis of locally advanced and recurrent or metastatic breast cancer with stage III/IV and had tissue HER2 status determinations using IHC/FISH. For the whole 224 advanced breast cancer patients, the sensitivity between dPCR in plasma and IHC/FISH in tissue samples is 43.75% (42/96), the specificity is 84.38% (108/128) and the overall concordance is 66.96% (150/224). Interestingly, when we looked at stage III, stage IV and recurrent or metastatic breast cancer separately, compared with IHC/FISH in tissue samples, the sensitivity of dPCR in plasma increases from 37.93% (11/29) for stage III to 41.67% (15/36) for stage IV cancer. Recurrent breast cancer patient had an increased sensitivity of 51.61% (16/31). This is consistent with our expectation sensitivity would increase concordantly as tumor burden goes up. On the other hand, specificity decreased from 92.68% (38/41) for stage III to 86.44% (51/59) for stage IV cancer. Recurrent breast cancer patient had a specificity of only 67.86% (19/28). This is, in part, due to inter- and intra-tumor heterogeneity. Many patients determined to be negative for HER2 amplification in tissue biopsy could have HER2 positive tumors at other sites, which was detected by the liquid biopsy. This study suggested the necessity of liquid biopsy for HER2 amplification detection and demonstrated digital PCR can be used as a companion diagnostic tool to determine HER2 amplification status. It also suggested that a liquid biopsy should follow a negative result from tissue biopsy to avoid false negative results especially for late-stage breast cancer patients and ones who experienced relapse or became resistant to current therapy. Future studies should focus on therapeutic effects on patients determined to be HER2 positive through liquid biopsy and collecting additional tissue biopsies to identify HER2 positive tumor when the original tissue biopsy and liquid biopsy don't agree.

Keywords: HER2, liquid biopsy, tissue biopsy, sensitivity, digital PCR


Citation styles

APA
Xie, S., Wang, Y., Gong, Z., Li, Y., Yang, W., Liu, G., Li, J., Hu, X., Wang, Y., Tong, Y., Yuan, P., Si, Y., Kang, Y., Mao, Y., Qi, X., Liu, Y., Ou, J., Li, Z., Pan, X., Lv, Z., Kaji, K., Guo, L., Lu, R. (2022). Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients. Journal of Cancer, 13(3), 744-751. https://doi.org/10.7150/jca.66567.

ACS
Xie, S.; Wang, Y.; Gong, Z.; Li, Y.; Yang, W.; Liu, G.; Li, J.; Hu, X.; Wang, Y.; Tong, Y.; Yuan, P.; Si, Y.; Kang, Y.; Mao, Y.; Qi, X.; Liu, Y.; Ou, J.; Li, Z.; Pan, X.; Lv, Z.; Kaji, K.; Guo, L.; Lu, R. Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients. J. Cancer 2022, 13 (3), 744-751. DOI: 10.7150/jca.66567.

NLM
Xie S, Wang Y, Gong Z, Li Y, Yang W, Liu G, Li J, Hu X, Wang Y, Tong Y, Yuan P, Si Y, Kang Y, Mao Y, Qi X, Liu Y, Ou J, Li Z, Pan X, Lv Z, Kaji K, Guo L, Lu R. Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients. J Cancer 2022; 13(3):744-751. doi:10.7150/jca.66567. https://www.jcancer.org/v13p0744.htm

CSE
Xie S, Wang Y, Gong Z, Li Y, Yang W, Liu G, Li J, Hu X, Wang Y, Tong Y, Yuan P, Si Y, Kang Y, Mao Y, Qi X, Liu Y, Ou J, Li Z, Pan X, Lv Z, Kaji K, Guo L, Lu R. 2022. Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients. J Cancer. 13(3):744-751.

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