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Utilization of Circulating Tumor Cells to Help 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 is human epidermal growth factor receptor 2 (HER2) positive. HER2 receptor conversion may occur during the course of treatment, and at some point, as the disease progresses.

It may be challenging 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 has been proposed as a noninvasive, cost-effective method that can be conducted contemporaneously that allows for tumor analysis as well as 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.

Regardless of subtype, recruited patients with metastatic breast cancer received at least 1 line of therapy, as appropriate, ranging from anti-HER2 therapy, chemotherapy, to hormone therapy.

HER2 status on tumor biopsies was analyzed for a mean of 7.3 months (range, 0-43 months) before enrolling in IMAGE, and circulating tumor cells were isolated 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. Circulating tumor cells were analyzed for HER2 amplification by fluorescence in situ hybridization. For each patient, the HER2 biomarker expression profile on the circulating tumor cells and metastatic tumor was assessed and evaluated.

For peripheral blood samples collected within 5 weeks of the tumor biopsy in the 36 evaluable patients, the specificity of HER2 on circulating tumor cells to tissue was 92.9% 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%.

In more than one-third (36%) of patients, a change in HER2 amplification between the metastatic tumor and circulating tumor cells was noted, 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.

A high level of accuracy of HER2 amplification on circulating tumor cells at both baseline and within 10 weeks of treatment is supported by these data, thereby suggesting 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.

Identifying 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, is one of the benefits of being capable of effectively and contemporaneously monitoring HER2 status on circulating tumor cells.

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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