Detection of cancer DNA in plasma of patients with early-stage breast cancer

Julia Beaver, Danijela Jelovac, Sasidharan Balukrishna, Rory L. Cochran, Sarah Croessmann, Daniel J. Zabransky, Hong Yuen Wong, Patricia Valda Toro, Justin Cidado, Brian G. Blair, David Chu, Timothy Burns, Michaela J. Higgins, Vered Stearns, Lisa Jacobs, Mehran Habibi, Julie R Lange, Paula Hurley, Josh Lauring, Dustin A. VanDenBerg & 9 others Jill Kessler, Stacie Jeter, Michael L. Samuels, Dianna Maar, Leslie Cope, Ashley M Cimino-Mathews, Pedram Argani, Antonio C Wolff, Ben Ho Park

Research output: Contribution to journalArticle

Abstract

Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design: In this prospective study, primary breast tumors and matched pre-and postsurgery blood samples were collected from patients with early-stage breast cancer (n=29). Tumors (n=30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n=29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.

Original languageEnglish (US)
Pages (from-to)2643-2650
Number of pages8
JournalClinical Cancer Research
Volume20
Issue number10
DOIs
StatePublished - May 15 2014

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Breast Neoplasms
DNA
Mutation
Neoplasms
Polymerase Chain Reaction
Exons
Prospective Studies
Research Design
Recurrence
Drug Therapy
Sensitivity and Specificity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Beaver, J., Jelovac, D., Balukrishna, S., Cochran, R. L., Croessmann, S., Zabransky, D. J., ... Park, B. H. (2014). Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clinical Cancer Research, 20(10), 2643-2650. https://doi.org/10.1158/1078-0432.CCR-13-2933

Detection of cancer DNA in plasma of patients with early-stage breast cancer. / Beaver, Julia; Jelovac, Danijela; Balukrishna, Sasidharan; Cochran, Rory L.; Croessmann, Sarah; Zabransky, Daniel J.; Wong, Hong Yuen; Toro, Patricia Valda; Cidado, Justin; Blair, Brian G.; Chu, David; Burns, Timothy; Higgins, Michaela J.; Stearns, Vered; Jacobs, Lisa; Habibi, Mehran; Lange, Julie R; Hurley, Paula; Lauring, Josh; VanDenBerg, Dustin A.; Kessler, Jill; Jeter, Stacie; Samuels, Michael L.; Maar, Dianna; Cope, Leslie; Cimino-Mathews, Ashley M; Argani, Pedram; Wolff, Antonio C; Park, Ben Ho.

In: Clinical Cancer Research, Vol. 20, No. 10, 15.05.2014, p. 2643-2650.

Research output: Contribution to journalArticle

Beaver, J, Jelovac, D, Balukrishna, S, Cochran, RL, Croessmann, S, Zabransky, DJ, Wong, HY, Toro, PV, Cidado, J, Blair, BG, Chu, D, Burns, T, Higgins, MJ, Stearns, V, Jacobs, L, Habibi, M, Lange, JR, Hurley, P, Lauring, J, VanDenBerg, DA, Kessler, J, Jeter, S, Samuels, ML, Maar, D, Cope, L, Cimino-Mathews, AM, Argani, P, Wolff, AC & Park, BH 2014, 'Detection of cancer DNA in plasma of patients with early-stage breast cancer', Clinical Cancer Research, vol. 20, no. 10, pp. 2643-2650. https://doi.org/10.1158/1078-0432.CCR-13-2933
Beaver, Julia ; Jelovac, Danijela ; Balukrishna, Sasidharan ; Cochran, Rory L. ; Croessmann, Sarah ; Zabransky, Daniel J. ; Wong, Hong Yuen ; Toro, Patricia Valda ; Cidado, Justin ; Blair, Brian G. ; Chu, David ; Burns, Timothy ; Higgins, Michaela J. ; Stearns, Vered ; Jacobs, Lisa ; Habibi, Mehran ; Lange, Julie R ; Hurley, Paula ; Lauring, Josh ; VanDenBerg, Dustin A. ; Kessler, Jill ; Jeter, Stacie ; Samuels, Michael L. ; Maar, Dianna ; Cope, Leslie ; Cimino-Mathews, Ashley M ; Argani, Pedram ; Wolff, Antonio C ; Park, Ben Ho. / Detection of cancer DNA in plasma of patients with early-stage breast cancer. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 10. pp. 2643-2650.
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abstract = "Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design: In this prospective study, primary breast tumors and matched pre-and postsurgery blood samples were collected from patients with early-stage breast cancer (n=29). Tumors (n=30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n=29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3{\%}, specificity 100{\%}). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.",
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T1 - Detection of cancer DNA in plasma of patients with early-stage breast cancer

AU - Beaver, Julia

AU - Jelovac, Danijela

AU - Balukrishna, Sasidharan

AU - Cochran, Rory L.

AU - Croessmann, Sarah

AU - Zabransky, Daniel J.

AU - Wong, Hong Yuen

AU - Toro, Patricia Valda

AU - Cidado, Justin

AU - Blair, Brian G.

AU - Chu, David

AU - Burns, Timothy

AU - Higgins, Michaela J.

AU - Stearns, Vered

AU - Jacobs, Lisa

AU - Habibi, Mehran

AU - Lange, Julie R

AU - Hurley, Paula

AU - Lauring, Josh

AU - VanDenBerg, Dustin A.

AU - Kessler, Jill

AU - Jeter, Stacie

AU - Samuels, Michael L.

AU - Maar, Dianna

AU - Cope, Leslie

AU - Cimino-Mathews, Ashley M

AU - Argani, Pedram

AU - Wolff, Antonio C

AU - Park, Ben Ho

PY - 2014/5/15

Y1 - 2014/5/15

N2 - Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design: In this prospective study, primary breast tumors and matched pre-and postsurgery blood samples were collected from patients with early-stage breast cancer (n=29). Tumors (n=30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n=29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.

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