Abstract P4-01-02: Early detection of residual breast cancer through a robust, scalable and personalized analysis of circulating tumour DNA (ctDNA) antedates overt metastatic recurrence
العنوان: | Abstract P4-01-02: Early detection of residual breast cancer through a robust, scalable and personalized analysis of circulating tumour DNA (ctDNA) antedates overt metastatic recurrence |
---|---|
المؤلفون: | Anna Rita Boydell, Robert K. Hastings, Samantha Navarro, Karen Page, Svetlana Shchegrova, R. C. Coombes, K. Goddard, Daniel Fernandez-Garcia, Raheleh Salari, L Primrose, Anne C Armstrong, Farah Rehman, Maggie C. Louie, Himanshu Sethi, Mustafa Balcioglu, David Moore, Bradley J. Toghill, Ja Shaw, C-Hj Lin, David S. Guttery, Samreen Ahmed, Bernhard Zimmermann, Zoe June Assaf, Kelly L. T. Gleason, Alexey Aleshin |
المصدر: | Cancer Research. 79:P4-01 |
بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Breast cancer recurrence, Early detection, Cancer, Physical examination, medicine.disease, Breast cancer, Internal medicine, Gene panel, medicine, Adjuvant therapy, business, Exome |
الوصف: | Background: Many breast cancer patients relapse after primary treatment but there are no reliable tests to detect distant metastases before they become overt. Here we show earlier identification of recurring patients through a scalable personalised ctDNA analysis. The method is applicable to all patients, and not limited to hot-spot mutations typically detected by gene panels. Methods: Forty-nine non-metastatic breast cancer patients were recruited following surgery and adjuvant therapy. Plasma samples (n=208) were serially collected semi-annually. Using the analytically validated SignateraTM workflow, we determined mutational signatures from primary tumour whole exome data and designed personalised assays targeting 16 variants with high sensitivity by ultra-deep sequencing (average >100,000X). The patient-specific assay was used to detect the presence of the mutational signature in the plasma. Results: In 16 of 18 (89%) clinically-relapsing patients, ctDNA was detected ahead of metastatic relapse being diagnosed by clinical examination, radiological and biochemical (CA15-3) measurements, and remained ctDNA-positive through follow-up. Of the 2 patients not detected by ctDNA, one had a small local recurrence only (now resected) and the other had three primary tumours. None of the 31 non-relapsing patients were ctDNA-positive at any time point (n=142). Metastatic relapse was predicted by Signatera with high accuracy and a lead time of up to 2 years (median=9.5 months). Conclusions: The use of a scalable patient-specific ctDNA-based validated workflow detects breast cancer recurrence ahead of clinical detection. Accurate and earlier prediction by ctDNA analysis could provide a means of monitoring breast cancer patients in need of second-line salvage adjuvant therapy in order to prevent overt life-threatening metastatic progression. Citation Format: Coombes RC, Armstrong A, Ahmed S, Page K, Hastings RK, Salari R, Sethi H, Boydell A-R, Shchegrova SV, Fernandez-Garcia D, Gleason KL, Goddard K, Guttery DS, Assaf ZJ, Balcioglu M, Moore DA, Primrose L, Navarro SL, Aleshin A, Rehman F, Toghill BJ, Louie MC, Zimmermann BG, Lin C-HJ, Shaw JA. Early detection of residual breast cancer through a robust, scalable and personalized analysis of circulating tumour DNA (ctDNA) antedates overt metastatic recurrence [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 P4-01-02. |
تدمد: | 1538-7445 0008-5472 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::5ecb7090f2b57aeef5ec8c7a374e3f7f https://doi.org/10.1158/1538-7445.sabcs18-p4-01-02 |
رقم الأكسشن: | edsair.doi...........5ecb7090f2b57aeef5ec8c7a374e3f7f |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15387445 00085472 |
---|