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Therapeutic Role of Tamoxifen for Triple-Negative Breast Cancer: Leveraging the Interaction Between ERβ and Mutant

Lauren Scarpetti1, Chetan C Oturkar2, Dejan Juric1

  • 1Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.

The Oncologist
|February 11, 2023
PubMed

Insights

Tamoxifen shows promise for treating triple-negative breast cancer (TNBC) with mutant p53 and brain metastases. This therapy increased estrogen receptor beta (ERβ) expression, leading to tumor regression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature and lack of effective therapeutic targets.
  • Estrogen receptor beta (ERβ) expression in TNBC is inconsistent, and its functional role remains debated.
  • Emerging evidence suggests potential therapeutic utility of ERβ in conjunction with mutant p53.

Purpose of the Study:

  • To investigate the efficacy of tamoxifen, a selective estrogen receptor modulator, in a patient with p53-mutant TNBC and brain metastases.
  • To explore the interaction between mutant p53 and ERβ following tamoxifen treatment.

Main Methods:

  • Case study analysis of a patient with p53-mutant, ERβ-positive TNBC and brain metastases.
  • Assessment of ERβ protein expression levels.
  • Evaluation of the anti-proliferative effects and tumor response after tamoxifen cessation.

Main Results:

  • Tamoxifen therapy cessation was associated with a significant increase in ERβ protein expression.
  • An anti-proliferative interaction between mutant p53 and ERβ was observed.
  • Significant regression of brain metastases was noted.

Conclusions:

  • This case study supports the potential use of tamoxifen in treating p53-mutant, ERβ-positive TNBC.
  • Tamoxifen may be particularly beneficial in TNBC patients with brain metastases.
  • Further research is warranted to validate these findings in a larger cohort.
Keywords:
brain metastasisestrogen receptor βmutant p53proximity ligation assay (PLA)tamoxifentriple-negative breast cancer

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