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Photograph of Maria Inasu

Maria Inasu

Researcher, PhD

Photograph of Maria Inasu

High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer

Author

  • Maria Inasu
  • Pär Ola Bendahl
  • Mårten Fernö
  • Per Malmström
  • Signe Borgquist
  • Siker Kimbung

Summary, in English

27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HRadj = 0.26, 95% CI = 0.07–0.93 and HRadj = 0.13, 95% CI = 0.03–0.60, respectively. In vitro studies revealed that 27HC treatment potently inhibited ER+ BC cell proliferation under lipid-depleted conditions regardless of estradiol levels, transcriptionally mediated through the downregulation of ER signaling with a concomitant upregulation of cholesterol export. Importantly, if validated, these results may have implications for adjuvant treatment decisions in premenopausal patients, especially when de-escalation of therapy is being considered.

Department/s

  • Breast cancer prevention & intervention
  • LUCC: Lund University Cancer Centre
  • Personalized Breast Cancer Treatment
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Breast cancer treatment

Publishing year

2021-12-01

Language

English

Publication/Series

npj Breast Cancer

Volume

7

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Breast cancer prevention & intervention
  • Personalized Breast Cancer Treatment
  • The Liquid Biopsy and Tumor Progression in Breast Cancer

ISBN/ISSN/Other

  • ISSN: 2374-4677