Obesity and metabolic syndrome are associated with short-term endocrine therapy resistance in early ER + breast cancer

Riley Bergman, Yvonne A. Berko, Violeta Sanchez, Melinda E. Sanders, Paula I. Gonzalez-Ericsson, Carlos L. Arteaga, Brent N. Rexer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Increased body mass index (BMI) and metabolic syndrome (MS) are associated with increased breast cancer recurrence risk. Whether this is due to intrinsic tumor biology or modifiable factors of the obese state remains incompletely understood. Methods: Oncotype DX Recurrence Scores of 751 patients were stratified by BMI to assess association with tumor-intrinsic recurrence risk. Cellular proliferation by Ki67 after 10–21 days of presurgical letrozole treatment was used to stratify endocrine therapy response (sensitive—ln(Ki67) < 1; intermediate—ln(Ki67)1–2; resistant—ln(Ki67) > = 2). BMI at the time of surgery and MS variables were collected retrospectively for 143 patients to analyze association between therapy response and BMI/MS. Additionally, PI3K pathway signaling was evaluated by immunohistochemistry of phosphorylated Akt and S6. Results: There was no significant association between BMI and recurrence score (p = 0.99), and risk score distribution was similar across BMI groups. However, BMI was associated with short-term endocrine therapy resistance, with a significant enrichment of intermediate and resistant tumors in patients with obesity (55%, p = 0.0392). Similarly, the relative risk of an endocrine therapy-resistant tumor was 1.4-fold greater for patients with MS (p = 0.0197). In evaluating PI3K pathway mediators, we found patients with 3 or more MS criteria had more tumors with pAkt scores above the median (p = 0.0436). There were no significant differences in S6 activation. Conclusion: Our findings suggest the association between obesity/metabolic syndrome and breast cancer recurrence is better reflected by response to treatment than tumor-intrinsic properties, suggesting interventions to reverse obesity and/or MS may improve outcomes for breast cancer recurrence.

Original languageEnglish (US)
Pages (from-to)307-317
Number of pages11
JournalBreast Cancer Research and Treatment
Volume197
Issue number2
DOIs
StatePublished - Jan 2023
Externally publishedYes

Keywords

  • Breast cancer
  • Endocrine therapy resistance
  • Metabolic syndrome
  • Obesity
  • Recurrence risk

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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