Use of Circulating Tumor Cells to Guide Treatment with HER2 Therapy

Conference Correspondent 

Notwithstanding advancements in early detection, over the course of a lifetime, 12% of women in the United States will develop invasive breast cancer. Nearly 20% of breast cancer cases are human epidermal growth factor receptor 2 (HER2) positive. HER2 receptor conversion may occur during treatment, and at some point, as the disease progresses.

It can be a challenge to access numerous metastatic sites or perform serial biopsies if the cancer metastasizes. Because tissue biopsy is fundamentally confined by a single time-point collection, and sampling precision is limited by intertumoral and intratumoral heterogeneity, the precision of these biopsy results may be less than optimal. A liquid biopsy could represent a noninvasive, cost-effective method that can be conducted contemporaneously, allowing for tumor analysis and circulating tumor DNA or circulating tumor cells.

Vered Stearns of Johns Hopkins, Baltimore, MD, and colleagues used a prospective analysis of the Individualized Molecular Analyses Guide Efforts in Breast Cancer (IMAGE) II study to define the expression of HER2 in metastatic tumors to HER2 amplification in circulating tumor cells.

Patients in the study with metastatic breast cancer, regardless of subtype, received at least 1 line of therapy, as appropriate, including anti-HER2 therapy, chemotherapy, and/or hormone therapy.

The researchers analyzed HER2 status on tumor biopsies for a mean of 7.3 months (range, 0-43 months) before enrolling in IMAGE, and isolated circulating tumor cells from peripheral blood drawn preferably prior to initiating new therapy, 1 to 2 weeks after beginning a new therapy and during the period of first restaging. They analyzed circulating tumor cells for HER2 amplification by fluorescence in situ hybridization. For each patient, they also assessed and evaluated the HER2 biomarker expression profile on the circulating tumor cells and metastatic tumor.

The specificity of HER2 on circulating tumor cells to tissue was 92.9% for peripheral blood samples collected within 5 weeks of the tumor biopsy in the 36 evaluable patients and 100% for peripheral blood samples collected between 5 and 10 weeks post biopsy, with specificity of 79.7%, accuracy of 76.5%, and overall concordance of 65%.

A change in HER2 amplification between the metastatic tumor and circulating tumor cells was noted in more than one-third (36%) of patients, with 7 patients HER2-positive in tissue, HER2-negative on circulating tumor cells and 8 patients HER2-negative on tissue, HER2-positive on circulating tumor cells.

These data support a high level of accuracy of HER2 amplification on circulating tumor cells at both baseline and within 10 weeks of treatment. This suggests that this tool has a high level of sensitivity and specificity when monitoring changes in HER2 status, helping to overcome challenges of biopsy caused by tissue heterogeneity or receptor switch.

Having the means to effectively and contemporaneously monitor HER2 status on circulating tumor cells confers several benefits, including the ability to identify patients who may gain from receiving anti-HER2 therapy supplementation or who are on anti-HER2 therapy but are not well-suited for it or may want to consider alternate treatment options.

Source: Stearns V, Lehman J, Mitchell C, et al. Her2 expression in matched metastatic tumor and circulating tumor cells (ctcs) in breast cancer: implications for profiling and monitoring of her2 status to help guide anti-her2 therapy. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS2-14.

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