Estrogen receptor beta expression in triple negative breast cancers is not associated with recurrence or survival

BMC Cancer. 2023 May 19;23(1):459. doi: 10.1186/s12885-023-10795-5.

Abstract

Background: Triple negative BCa (TNBC) is defined by a lack of expression of estrogen (ERα), progesterone (PgR) receptors and human epidermal growth factor receptor 2 (HER2) as assessed by protein expression and/or gene amplification. It makes up ~ 15% of all BCa and often has a poor prognosis. TNBC is not treated with endocrine therapies as ERα and PR negative tumors in general do not show benefit. However, a small fraction of the true TNBC tumors do show tamoxifen sensitivity, with those expressing the most common isoform of ERβ1 having the most benefit. Recently, the antibodies commonly used to assess ERβ1 in TNBC have been found to lack specificity, which calls into question available data regarding the proportion of TNBC that express ERβ1 and any relationship to clinical outcome.

Methods: To confirm the true frequency of ERβ1 in TNBC we performed robust ERβ1 immunohistochemistry using the specific antibody CWK-F12 ERβ1 on 156 primary TNBC cancers from patients with a median of 78 months (range 0.2-155 months) follow up.

Results: We found that high expression of ERβ1 was not associated with increased recurrence or survival when assessed as percentage of ERβ1 positive tumor cells or as Allred > 5. In contrast, the non-specific PPG5-10 antibody did show an association with recurrence and survival.

Conclusions: Our data indicate that ERβ1 expression in TNBC tumours does not associate with prognosis.

Keywords: Estrogen receptor beta; Outcome; Prognosis; Sensitivity; Tamoxifen; Triple negative breast cancer.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor beta / genetics
  • Female
  • Humans
  • Prognosis
  • Receptor, ErbB-2 / therapeutic use
  • Receptors, Estrogen
  • Receptors, Progesterone / metabolism
  • Tamoxifen / therapeutic use
  • Triple Negative Breast Neoplasms* / metabolism

Substances

  • Estrogen Receptor beta
  • Estrogen Receptor alpha
  • Tamoxifen
  • Receptors, Estrogen
  • Receptor, ErbB-2
  • Receptors, Progesterone