Dataset Information

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

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.

SUBMITTER: Horimoto Y

PROVIDER: S-EPMC4453454 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

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

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

British journal of cancer 20141125 2

<h4>Background</h4>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.<h4>Methods</h4>Biopsy specimens from 103 luminal HER2-negative tumours were immunohist ...[more]

PMID: 25422910

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Project description:BackgroundPatients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy. However, the significance of chemotherapy for those with luminal tumours has decreased due to recent changes in treatment strategies. Thus, it is often difficult to determine whether we should recommend chemotherapy to such patients in clinical practice. We investigated Ki67 expression, as a means of predicting the responses of luminal HER2-negative breast cancer patients to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that would benefit from these treatments.MethodsWe enrolled 114 luminal HER2-negative breast cancer patients undergoing surgery after NAC. Biomarkers were examined using biopsy specimens obtained prior to treatment, to avoid any chemotherapy-related effects. Chemotherapy effects were determined employing operative specimens and we defined pathological complete response (pCR) as invasive nest disappearance, based only on the primary breast tumour. We applied receiver operating characteristic curve analysis to data from our 114 patients, to investigate Ki67 expression as a predictor of pCR.ResultsThe pCR rate was significantly higher for tumours with high Ki67 expression (p < 0.01) and all patients who obtained pCR remained recurrence-free during the median 58-month observation period. We identified 35% as the Ki67 cut-off value which distinguishes those with a pCR from other cases. Another dataset, comprised of 196 patients with a median 29-month observation period, was recruited for validation. Disease-free survival was found to be significantly (p < 0.01) lower in the patients with tumours in which Ki67 expression was higher than 35%.ConclusionOur results raise the possibility of the luminal HER2-negative subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy, as evidenced by improved survival.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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