CLO21-024: Serial Circulating Tumor DNA Analysis for Treatment Monitoring in an Inflammatory Triple-Negative Breast Cancer Patient

Authors:
Urmeel PatelMillennium Physicians, The Woodlands, TX

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 MD
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Nicole HookNatera Inc., San Carlos, CA

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 MS, CGC
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Meenakshi MalhotraNatera Inc., San Carlos, CA

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 PhD
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Perry OlshanNatera Inc., San Carlos, CA

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Paul R. BillingsNatera Inc., San Carlos, CA

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 MD, PhD
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Alexey AleshinNatera Inc., San Carlos, CA

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 MD, MBA
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Angel RodriguezNatera Inc., San Carlos, CA

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Introduction: Triple negative breast cancer (TNBC) is an aggressive form of cancer that lacks hormone and growth factor receptors. The recommended therapy for TNBC includes a wide range of chemo- and immunotherapies. However, a need exists for a robust biomarker that quickly adapts with the molecular changes of the disease and informs on optimizing/change in treatment strategy. Methods: Here we present a case study of a 57-year-old female with stage lIlB, T4dN2aM0, inflammatory TNBC. The patient underwent neoadjuvant chemotherapy with dose dense AC (ddAC) followed by paclitaxel. Following one month, the patient underwent radical mastectomy, followed by adjuvant treatment and periodic radiological imaging, along with circulating tumor DNA (ctDNA) analysis using assay Signature®, (bespoke mPCR NGS assay) to identify molecular residual disease and treatment response. Results: The patient achieved partial response to ddAC but eventually progressed after paclitaxel. Pathological reports post-surgery confirmed inflammatory breast cancer. ctDNA analysis performed 2 weeks post-surgery revealed a ctDNA positive status (1.81) MTM/mL. Due to the post surgical site infection, a repeat biopsy of the wound and a PET/CT scan performed two months after surgery confirmed inflammatory metastatic breast cancer. The patient then underwent treatment with capecitabine along with radiotherapy with response noted on examination of skin. Following 3 months of treatment, a repeat ctDNA analysis showed an increase to 3.72 MTM/mL corresponding with disease progression on imaging. Separate tissue analysis performed using a comprehensive genomic profiling test revealed a PD-L1 expression of 1%. Due to continued progression, the patient was initiated on nab-paclitaxel and atezolizumab with baseline ctDNA level of 31.37 MTM/mL. Following the change in therapy, the patient experienced decline in ctDNA levels 0.88 MTM/mL and concurrently achieved clinical response with subsequent CT scans indicating stable disease. However, 5 months after, a rise in ctDNA level (8.1 MTM/mL) was reported, followed by disease progression on CT which led to switch to an alternative therapy with sacituzumab govitecan. Conclusion: ctDNA assay enables prognostic stratification in a patient with inflammatory breast cancer and serial monitoring enables early detection of response/resistance to therapy prompting a timely change to an alternative therapy than the current standard of care.

Corresponding Author: Meenakshi Malhotra, PhD
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