Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR

Sung Gwe Ahn, Soong June Bae, Yoonjung Kim, Jung Hwan Ji, Chihhao Chu, Dooreh Kim, Janghee Lee, Yoon Jin Cha, Kyung A. Lee, Joon Jeong

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.

Original languageEnglish
Article number58
Journalnpj Breast Cancer
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This study was supported by the Hao Lin Chu Research Grant of Gangnam Severance Cancer Hospital.

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)


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