The use of minimal residual disease in patients with high-risk breast cancer.

Abstract

e12521 Background: Breast cancer is the most frequently diagnosed cancer worldwide and the second leading cause of cancer death in women in the United States. Despite being disease-free after primary treatment, studies have shown that up to 30% of patients present with disease recurrence. Circulating tumor DNA (ctDNA) in blood is a minimally invasive technique to characterize individual cancer biology and monitor disease. Previous studies have demonstrated that ctDNA can be a sensitive and specific approach to breast cancer follow up and surveillance of disease recurrence for all subtypes. Methods: We evaluated 38 high risk breast cancer patients utilizing a personalized and tumor-informed ctDNA assay at 3-6 month intervals. We defined high risk as: any stage III disease, triple negative breast cancer (TNBC) or HR-/HER2+ breast cancer who received neoadjuvant chemotherapy treatment (NACT), pregnancy associated breast cancer, metastatic breast cancer without any evidence of disease, history of bilateral breast cancer, high risk genetics (i.e. BRCA1 or BRCA2 mutations), young age at diagnosis (<40 years old) and/or breast cancer recurrence of any subtype. Results: Patient ages ranged from 34 to 83 (average: 53.3 years old) and included a diverse race/ethnicity population: White (n=12, 31%), Japanese (n=9, 23.7%), Native Hawaiian (n=6, 15.8%), Chinese (n=4, 10.5%), Filipino (n=4, 10.5%), Black (n=1, 2.6%), Hispanic (n=1, 2.6%), and Korean (n=1, 2.6%). Of the 38 cases, there was one ctDNA positive finding seen in a high risk case (young age at diagnosis and BRCA2 mutation) of clinical stage IIA HR+/HER2- breast cancer. After NACT, bilateral mastectomies, and radiation, patient remained on tamoxifen (declined ovarian function suppression) and was initially ctDNA negative until a second test identified detectable ctDNA. Restaging scans however did not show any evidence of disease. A third ctDNA test three months later, continued to be positive without any evidence of disease. All other cases showed negative ctDNA testing with an average of 1.55 ctDNA tests done per patient over two years. However, one case of clinical stage IIB TNBC had contralateral recurrence despite negative testing. After receiving NACT, bilateral mastectomies, post-operative paclitaxel and radiation, two ctDNA tests done three months apart were negative. Conclusions: There is potential use for this ctDNA platform in high risk breast cancer patients but larger studies need to be done. [Table: see text]