Abstract P4-01-16: Detection of plasma tumor DNA (ptDNA) in patients with hormone receptor-positive HER2-negative (HR+HER2-) early breast cancer (EBC) in clinical remission
Authors: Shah M , Hunter N , Ensminger J , Shinn D , Cole AJ , Quinn HE , Edelstein DL , Wang C , Smith KL , Richardson AL , Cimino-Mathews A , Wolff AC , Cravero K , Park BH , Stearns V 
Published: May 2019

Abstract
Background: Detection of ptDNA in patients with HR+HER2- EBC in clinical remission may impact recommendations for type and duration of adjuvant endocrine therapy. A sensitive technique to identify tumor mutations in plasma is BEAMing digital PCR. The frequency and timing of detectable mutations in plasma of patients in clinical remission from HR+HER2- EBC are unknown.
Methods: We screened a prospective institutional repository for patients that met inclusion criteria. Eligible patients must have been enrolled to the repository between 12/1/2008 (repository start) and 12/31/2016, had HR+HER2- EBC, received follow-up at Johns Hopkins with appointment scheduled between 3/1/2017 and 12/31/2017, completed curative surgery at least 6 months prior to this appointment, been recommended or initiated adjuvant endocrine therapy, and been in clinical remission. Appropriate patients were approached for a current blood sample during their follow-up appointment in 2017. Blood was analyzed using a BEAMing digital PCR platform (Sysmex Inostics OncoBEAM™) for AKT1, PIK3CA, and ESR1 mutations.
Results: We identified 67 eligible patients and collected blood from 60. Most patients had relatively low risk disease including 40 patients (67%) with stage I disease, and only 21 patients (35%) received chemotherapy. Patients were evenly divided between receiving tamoxifen or an aromatase inhibitor, and some patients switched from one to the other. The majority of patients (68%) had surgery between 1 and 5 years prior to the current blood draw. Detailed patient characteristics are provided in Table 1.
Two out of the 60 patients had detectable ptDNA, both with stage IIA disease. One patient had a mutation in the ESR1 ligand-binding domain P535H 9 months after surgery and while taking adjuvant tamoxifen for 7 months. Sanger sequencing of primary tumor tissue did not reveal this mutation. Another patient had a mutation in PIK3CA exon 9 E542K 9.5 years after surgery and after taking adjuvant tamoxifen for at least 7 years. Amplifying this locus in DNA from primary tumor tissue was unsuccessful; further analysis using droplet digital PCR (ddPCR) is planned.
Conclusions: Detection of ptDNA was feasible in a relatively low-risk group of patients with HR+HER2- EBC in clinical remission. Sampling a larger number of patients is needed to gain more understanding of the frequency and timing of detectable ptDNA. Next steps should also focus on determining the natural history of detectable ptDNA in patients with HR+HER2 EBC in clinical remission which may impact adjuvant treatment recommendations.
Funding sources: Komen SAC110053, P30 CA06973, Breast Cancer Research Foundation
Table 1:Characteristics of included patients N (%)Total patients60Age at diagnosis, median(range)57 (30-77)Female59 (98)Caucasian54 (90)Postmenopausal at diagnosis36 (60)Tumor size &lt;2 cm42 (70)Node negative45 (75)Invasive ductal histology44 (73)Received adjuvant chemotherapy21 (35)Type of adjuvant endocrine therapy Tamoxifen25 (42)Aromatase inhibitor26 (43)Tamoxifen and AI7 (12)None2 (3)Time after surgery 6 months to &lt;1 year6 (10)1 year to &lt;5 years41 (68)5 years to &lt;10 years13 (22)
Citation Format: Shah M, Hunter N, Ensminger J, Shinn D, Cole AJ, Quinn HE, Edelstein DL, Wang C, Smith KL, Richardson AL, Cimino-Mathews A, Wolff AC, Cravero K, Park BH, Stearns V. Detection of plasma tumor DNA (ptDNA) in patients with hormone receptor-positive HER2-negative (HR+HER2-) early breast cancer (EBC) in clinical remission [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-16.