1. Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer
- Author
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Stephen R. D. Johnston, Alistair Ring, Rosalind J. Cutts, Judith M Bliss, Ian E. Smith, Sarah Hrebien, Anthony Skene, Mitch Dowsett, S. Russell, Claire Swift, Divya Kriplani, Holly Tovey, Isaac Garcia-Murillas, Neha Chopra, M Afentakis, Matthew Beaney, Iñaki Comino-Mendez, Peter A. Barry, Duncan Wheatley, Giselle Walsh-Crestani, Abigail Evans, and Nicholas C. Turner
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Recurrence ,Interquartile range ,Internal medicine ,Biomarkers, Tumor ,medicine ,Adjuvant therapy ,Humans ,030212 general & internal medicine ,Prospective cohort study ,Aged ,business.industry ,Brief Report ,Hazard ratio ,Middle Aged ,medicine.disease ,Primary tumor ,030220 oncology & carcinogenesis ,Mutation ,Cohort ,Female ,Sample collection ,Neoplasm Recurrence, Local ,business - Abstract
IMPORTANCE: Current treatment cures most cases of early-stage, primary breast cancer. However, better techniques are required to identify which patients are at risk of relapse. OBJECTIVE: To assess the clinical validity of molecular relapse detection with circulating tumor DNA (ctDNA) analysis in early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, sample collection, validation study conducted at 5 United Kingdom medical centers from November 24, 2011, to October 18, 2016, assessed patients with early-stage breast cancer irrespective of hormone receptor and ERBB2 (formerly HER2 or HER2/neu) status who were receiving neoadjuvant chemotherapy followed by surgery or surgery before adjuvant chemotherapy. The study recruited 170 women, with mutations identified in 101 patients forming the main cohort. Secondary analyses were conducted on a combined cohort of 144 patients, including 43 patients previously analyzed in a proof of principle study. INTERVENTIONS: Primary tumor was sequenced to identify somatic mutations, and personalized tumor-specific digital polymerase chain reaction assays were used to monitor these mutations in serial plasma samples taken every 3 months for the first year of follow-up and subsequently every 6 months. MAIN OUTCOMES AND MEASURES: The primary end point was relapse-free survival analyzed with Cox proportional hazards regression models. RESULTS: In the main cohort of 101 female patients (mean [SD] age, 54 [11] years) with a median follow-up of 35.5 months (interquartile range, 27.9-43.0 months), detection of ctDNA during follow-up was associated with relapse (hazard ratio, 25.2; 95% CI, 6.7-95.6; P
- Published
- 2019