ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients

David Chu, Costanza Paoletti, Christina Gersch, Dustin A. VanDenBerg, Daniel J. Zabransky, Rory L. Cochran, Hong Yuen Wong, Patricia Valda Toro, Justin Cidado, Sarah Croessmann, Bracha Erlanger, Karen Cravero, Kelly Kyker-Snowman, Berry Button, Heather A. Parsons, William Dalton, Riaz Gillani, Arielle Medford, Kimberly Aung, Nahomi TokudomeArul M. Chinnaiyan, Anne Schott, Dan Robinson, Karen S. Jacks, Josh Lauring, Paula Hurley, Daniel F. Hayes, James M. Rae, Ben Ho Park

Research output: Contribution to journalArticle

Abstract

Purpose: Mutations in the estrogen receptor (ER)a gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumorDNA(ptDNA) from patients with metastatic breast cancer. Experimental Design: We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. Results: In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). Conclusions: We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion.

Original languageEnglish (US)
Pages (from-to)993-999
Number of pages7
JournalClinical Cancer Research
Volume22
Issue number4
DOIs
StatePublished - Feb 15 2016

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Breast Neoplasms
Mutation
DNA
Neoplasms
Estrogen Receptors
Mutation Rate
Biopsy
Polymerase Chain Reaction
Research Design
Neoplasm Metastasis
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chu, D., Paoletti, C., Gersch, C., VanDenBerg, D. A., Zabransky, D. J., Cochran, R. L., ... Park, B. H. (2016). ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients. Clinical Cancer Research, 22(4), 993-999. https://doi.org/10.1158/1078-0432.CCR-15-0943

ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients. / Chu, David; Paoletti, Costanza; Gersch, Christina; VanDenBerg, Dustin A.; Zabransky, Daniel J.; Cochran, Rory L.; Wong, Hong Yuen; Toro, Patricia Valda; Cidado, Justin; Croessmann, Sarah; Erlanger, Bracha; Cravero, Karen; Kyker-Snowman, Kelly; Button, Berry; Parsons, Heather A.; Dalton, William; Gillani, Riaz; Medford, Arielle; Aung, Kimberly; Tokudome, Nahomi; Chinnaiyan, Arul M.; Schott, Anne; Robinson, Dan; Jacks, Karen S.; Lauring, Josh; Hurley, Paula; Hayes, Daniel F.; Rae, James M.; Park, Ben Ho.

In: Clinical Cancer Research, Vol. 22, No. 4, 15.02.2016, p. 993-999.

Research output: Contribution to journalArticle

Chu, D, Paoletti, C, Gersch, C, VanDenBerg, DA, Zabransky, DJ, Cochran, RL, Wong, HY, Toro, PV, Cidado, J, Croessmann, S, Erlanger, B, Cravero, K, Kyker-Snowman, K, Button, B, Parsons, HA, Dalton, W, Gillani, R, Medford, A, Aung, K, Tokudome, N, Chinnaiyan, AM, Schott, A, Robinson, D, Jacks, KS, Lauring, J, Hurley, P, Hayes, DF, Rae, JM & Park, BH 2016, 'ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients', Clinical Cancer Research, vol. 22, no. 4, pp. 993-999. https://doi.org/10.1158/1078-0432.CCR-15-0943
Chu D, Paoletti C, Gersch C, VanDenBerg DA, Zabransky DJ, Cochran RL et al. ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients. Clinical Cancer Research. 2016 Feb 15;22(4):993-999. https://doi.org/10.1158/1078-0432.CCR-15-0943
Chu, David ; Paoletti, Costanza ; Gersch, Christina ; VanDenBerg, Dustin A. ; Zabransky, Daniel J. ; Cochran, Rory L. ; Wong, Hong Yuen ; Toro, Patricia Valda ; Cidado, Justin ; Croessmann, Sarah ; Erlanger, Bracha ; Cravero, Karen ; Kyker-Snowman, Kelly ; Button, Berry ; Parsons, Heather A. ; Dalton, William ; Gillani, Riaz ; Medford, Arielle ; Aung, Kimberly ; Tokudome, Nahomi ; Chinnaiyan, Arul M. ; Schott, Anne ; Robinson, Dan ; Jacks, Karen S. ; Lauring, Josh ; Hurley, Paula ; Hayes, Daniel F. ; Rae, James M. ; Park, Ben Ho. / ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 4. pp. 993-999.
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T1 - ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients

AU - Chu, David

AU - Paoletti, Costanza

AU - Gersch, Christina

AU - VanDenBerg, Dustin A.

AU - Zabransky, Daniel J.

AU - Cochran, Rory L.

AU - Wong, Hong Yuen

AU - Toro, Patricia Valda

AU - Cidado, Justin

AU - Croessmann, Sarah

AU - Erlanger, Bracha

AU - Cravero, Karen

AU - Kyker-Snowman, Kelly

AU - Button, Berry

AU - Parsons, Heather A.

AU - Dalton, William

AU - Gillani, Riaz

AU - Medford, Arielle

AU - Aung, Kimberly

AU - Tokudome, Nahomi

AU - Chinnaiyan, Arul M.

AU - Schott, Anne

AU - Robinson, Dan

AU - Jacks, Karen S.

AU - Lauring, Josh

AU - Hurley, Paula

AU - Hayes, Daniel F.

AU - Rae, James M.

AU - Park, Ben Ho

PY - 2016/2/15

Y1 - 2016/2/15

N2 - Purpose: Mutations in the estrogen receptor (ER)a gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumorDNA(ptDNA) from patients with metastatic breast cancer. Experimental Design: We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. Results: In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). Conclusions: We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion.

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