Impact of FOXA1 expression on the prognosis of patients with hormone receptor-positive breast cancer

Ann Surg Oncol. 2012 Apr;19(4):1145-52. doi: 10.1245/s10434-011-2094-4. Epub 2011 Oct 8.

Abstract

Background: Assessing indications for adjuvant chemotherapy (CT) in patients with hormone receptor (HR)-positive/human epidermal receptor 2 (HER2)-negative breast cancer remains a challenge for oncologists. In this study, we evaluated whether forkhead-box protein A1 (FOXA1) expression was a prognostic and predictive marker for HR-positive breast cancer.

Methods: FOXA1 expression was analyzed immunohistochemically in 239 primary breast cancers. Associations between FOXA1 expression and clinicopathological characteristics and prognosis were evaluated.

Results: FOXA1 expression was positively correlated with estrogen receptor (ER) (P<0.0001) and progesterone receptor (PR) expression (P=0.0011), and inversely correlated with nuclear grade (P=0.0048) and Ki67 index (P=0.0112). High FOXA1 was associated with longer recurrence-free survival (RFS) in all cases (P<0.0001) and in ER-positive cases (P<0.0001), but not in ER-negative cases. In addition, FOXA1 expression was associated with good prognosis, regardless of the Ki67 index, in HR-positive cases. FOXA1 was an independent prognostic factor on multivariate analysis in all cases and in ER-positive cases. Among HR-positive/HER2-negative cases with high FOXA1 expression, there was no difference in RFS between those given hormone therapy (HT) alone and those given CT plus HT.

Conclusions: In HR-positive breast cancer, FOXA1 expression was significantly associated with good prognosis. FOXA1 expression may be a useful marker for HR-positive/HER2-negative breast cancer to identify patients with good prognosis who may not require CT.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Chemoradiotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Phenobarbital / classification
  • Phenobarbital / metabolism
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2
  • Phenobarbital