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Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer.
Shaw, Jacqueline A; Page, Karen; Wren, Evie; de Bruin, Elza C; Kalashnikova, Ekaterina; Hastings, Robert; McEwen, Rob; Zhang, Eddie; Wadsley, Marc; Acheampong, Emmanuel; Renner, Derek; Gleason, Kelly L T; Ambasager, Bana; Stetson, Daniel; Fernandez-Garcia, Daniel; Guttery, David; Allsopp, Rebecca C; Rodriguez, Angel; Zimmermann, Bernhard; Sethi, Himanshu; Aleshin, Alexey; Liu, Minetta C; Richards, Cathy; Stebbing, Justin; Ali, Simak; Rehman, Farah; Cleator, Susan; Kenny, Laura; Ahmed, Samreen; Armstrong, Anne C; Coombes, R Charles.
Afiliación
  • Shaw JA; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Page K; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Wren E; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • de Bruin EC; Oncology R&D, Research & Early Development, AstraZeneca, Cambridge, United Kingdom.
  • Kalashnikova E; Oncology R&D, Research & Early Development, AstraZeneca, Waltham, MA.
  • Hastings R; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • McEwen R; Oncology R&D, Research & Early Development, AstraZeneca, Cambridge, United Kingdom.
  • Zhang E; Oncology R&D, Research & Early Development, AstraZeneca, Waltham, MA.
  • Wadsley M; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Acheampong E; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Renner D; Natera, Inc, Austin, TX.
  • Gleason KLT; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • Ambasager B; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • Stetson D; Oncology R&D, Research & Early Development, AstraZeneca, Waltham, MA.
  • Fernandez-Garcia D; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Guttery D; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Allsopp RC; Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
  • Rodriguez A; Natera, Inc, Austin, TX.
  • Zimmermann B; Natera, Inc, Austin, TX.
  • Sethi H; Natera, Inc, Austin, TX.
  • Aleshin A; Natera, Inc, Austin, TX.
  • Liu MC; Natera, Inc, San Carlos, CA.
  • Richards C; University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
  • Stebbing J; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • Ali S; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • Rehman F; Imperial College Healthcare NHS Trust, London, United Kingdom.
  • Cleator S; Imperial College Healthcare NHS Trust, London, United Kingdom.
  • Kenny L; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • Ahmed S; University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
  • Armstrong AC; Division of Cancer Sciences, The Christie NHS Foundation Trust, Manchester, United Kingdom.
  • Coombes RC; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
JCO Precis Oncol ; 8: e2300456, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38691816
ABSTRACT

PURPOSE:

Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer.

METHODS:

A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data.

RESULTS:

Personalized Signatera assays detected ctDNA ahead of clinical or radiologic relapse in 30 of the 34 patients who relapsed (patient-level sensitivity of 88.2%). Relapse was predicted with a lead interval of up to 38 months (median, 10.5 months; range, 0-38 months), and ctDNA positivity was associated with shorter relapse-free survival (P < .0001) and overall survival (P < .0001). All relapsing triple-negative patients (n = 7/23) had a ctDNA-positive test within a median of 8 months (range, 0-19 months), while the 16 nonrelapsed patients with triple-negative breast cancer remained ctDNA-negative during a median follow-up of 58 months (range, 8-99 months). The four patients who had negative tests before relapse all had hormone receptor-positive (HR+) disease and conversely, five of the 122 nonrelapsed patients (all HR+) had an occasional positive test.

CONCLUSION:

Serial postoperative ctDNA assessment has strong prognostic value, provides a potential window for earlier therapeutic intervention, and may enable more effective monitoring than current clinical tests such as cancer antigen 15-3. Our study provides evidence that those with serially negative ctDNA tests have superior clinical outcomes, providing reassurance to patients with breast cancer. For select cases with HR+ disease, decisions about treatment management might require serial monitoring despite the ctDNA-positive result.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / ADN Tumoral Circulante Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: JCO Precis Oncol Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / ADN Tumoral Circulante Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: JCO Precis Oncol Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos