Low FOXA1 expression predicts good response to neo-adjuvant chemotherapy resulting in good outcomes for luminal HER2-negative breast cancer cases

Y Horimoto; A Arakawa; N Harada-Shoji; H Sonoue; Y Yoshida; T Himuro; F Igari; E Tokuda; O Mamat; M Tanabe; O Hino; M Saito

doi:10.1038/bjc.2014.595

Low FOXA1 expression predicts good response to neo-adjuvant chemotherapy resulting in good outcomes for luminal HER2-negative breast cancer cases

Br J Cancer. 2015 Jan 20;112(2):345-51. doi: 10.1038/bjc.2014.595. Epub 2014 Nov 25.

Authors

Y Horimoto¹, A Arakawa², N Harada-Shoji³, H Sonoue², Y Yoshida⁴, T Himuro⁴, F Igari⁴, E Tokuda⁴, O Mamat², M Tanabe⁴, O Hino⁵, M Saito⁴

Affiliations

¹ 1] Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ Division of Cancer, Department of Surgery and Cancer, 1st Floor, ICTEM Building, Hammersmith Hospital, Imperial College London, London W12 0NN, UK.
⁴ Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
⁵ Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

Background: FOXA1 expression is a good prognostic marker for endocrine therapy in hormone-positive breast cancer. We retrospectively examined breast cancer patients with luminal human epidermal growth factor receptor 2 (HER2)-negative tumours, as defined by immunohistochemistry, who received neo-adjuvant chemotherapy (NAC) and investigated the relationship between treatment effects and FOXA1 expression.

Methods: Biopsy specimens from 103 luminal HER2-negative tumours were immunohistochemically examined. FOXA1 effects on chemo-sensitivity were also investigated employing in vitro experiments.

Results: FOXA1 and Ki67 expressions independently predicted a pathological complete response (pCR). Knockdown of FOXA1 by siRNA boosted the chemo-effect in oestrogen receptor-positive cells. The Cox hazards model revealed a pCR to be the strongest factor predicting a good patient outcome.

Conclusions: Our present study showed low FOXA1 expression to be associated with a good response to NAC in luminal HER2-negative breast cancer. Improved outcomes of these patients suggest that NAC should be recommended to patients with low FOXA1 tumours.

MeSH terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Breast Neoplasms / mortality
Bridged-Ring Compounds / administration & dosage
Carcinoma, Ductal, Breast / drug therapy
Carcinoma, Ductal, Breast / metabolism*
Carcinoma, Ductal, Breast / mortality
Cell Line, Tumor
Chemotherapy, Adjuvant
Cyclophosphamide / administration & dosage
Disease-Free Survival
Docetaxel
Epirubicin / administration & dosage
Female
Fluorouracil / administration & dosage
Gene Expression*
Gene Knockdown Techniques
Hepatocyte Nuclear Factor 3-alpha / genetics
Hepatocyte Nuclear Factor 3-alpha / metabolism*
Humans
Kaplan-Meier Estimate
Ki-67 Antigen / metabolism
Middle Aged
Neoadjuvant Therapy
Proportional Hazards Models
Receptor, ErbB-2 / metabolism
Receptors, Progesterone / metabolism
Retrospective Studies
Taxoids / administration & dosage
Treatment Outcome
Young Adult

Substances

Bridged-Ring Compounds
FOXA1 protein, human
Hepatocyte Nuclear Factor 3-alpha
Ki-67 Antigen
Receptors, Progesterone
Taxoids
Docetaxel
taxane
Epirubicin
Cyclophosphamide
ERBB2 protein, human
Receptor, ErbB-2
Fluorouracil