Background Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that is most difficult to treat due to the absence of hormone/growth factor receptors.^{1 2} Metastatic TNBC (mTNBC) is particularly challenging, given the limited efficacy and duration of response to chemotherapy.³ The repertoire of therapeutic options for mTNBC patients continues to increase with chemotherapeutic and immuno oncology based treatments and now includes sacituzumab govitecan, a novel antibody-chemotherapy conjugate.⁴

Methods Here we present a case study of a 40-year-old female who on biopsy of her left breast mass was diagnosed with TNBC. The patient underwent neoadjuvant chemotherapy with weekly administration of paclitaxel and carboplatin followed by dose-dense doxorubicin with cyclophosphamide. Following one-month, the patient underwent bilateral mastectomy, showing pathological staging ypT2 pN0. The patient underwent periodic radiological imaging along with the assessment of circulating tumor DNA in blood using a personalized and tumor-informed multiplex PCR, next-generation sequencing assay (Signatera bespoke, mPCR NGS assay) to identify the minimal residual disease (MRD) and treatment response.

Results After surgery, MRD assessment revealed ctDNA positive status (0.41 MTM/mL) prompting PET/CT scan that revealed liver metastasis. Continued ctDNA monitoring showed continuous increase in ctDNA concentration (287.09 MTM/mL). Separate analyses indicated MSI-high and PD-L1 positive tumor status, leading to the initiation of the first line of therapy (nab-paclitaxel and Atezolizumab), which resulted in ctDNA decline (39.62 MTM/ml). Weekly ctDNA monitoring noted a rapid increase a month later (178 MTM/ml to 833.69 MTM/ml) within a 2-week interval, which corresponded to disease progression on imaging. Given non-responsiveness with the first-line therapy, the patient was initiated with sacituzumab govitecan. Following this, a rapid decline in the ctDNA level was observed within a week (364.07 MTM/mL) with a downward trend to 73.03 MTM/ml by two weeks. An interval PET/CT scan showed a mixed response. Continued monitoring of ctDNA demonstrated ctDNA levels <5MTM/mL for a period of two months before serially rising again (to 89.27 MTM/ml). PET-CT ordered in response to increasing ctDNA levels confirmed progression involving hepatic and lung lesions. A new line of therapy with nivolumab and ipilimumab was subsequently initiated.

Conclusions Serial monitoring of ctDNA enables early detection of therapy resistance and provides a rationale for treatment change/optimization/discontinuation as compared to periodic imaging that is currently the standard of care. The ease and convenience of using ctDNA-based testing as frequently as every week clearly identified earlier non-responsiveness to IO and also identified earlier acquired resistance to antibody-drug conjugate, enabling a prompt switch to alternative therapy.

Ethics Approval N/A

Consent N/A

References

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2. Mehanna J, Haddad FG, Eid R, Lambertini M, Kourie HR. Triple-negative breast cancer: current perspective on the evolving therapeutic landscape. Int J Womens Health2019;11:431–437. Published 2019 Jul 31. doi:10.2147/IJWH.S178349

3. Treatment of Triple-negative Breast Cancer. American Cancer Society Website. Updated 2020. Accessed August 10, 2020. https://www.cancer.org/cancer/breast-cancer/treatment/treatment-of-triple-negative.html

4. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 2019;380(8):741–751. doi:10.1056/NEJMoa1814213