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CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy.

Abstract：

BACKGROUND:Doxorubicin-based chemotherapy is currently the most frequently used treatment for triple negative breast cancer (TNBC), yet the response rate is not high due to the lack of a biomarker allowing identification of responsive patients before the chemotherapy is initiated. We have demonstrated that doxorubicin inhibits proliferation of cancer cells through proteolytic activation of a transcription factor called CREB3L1 (cAMP response element binding protein 3-like 1), and that CREB3L1 expression in cancer cells is a key determinant of their sensitivity to doxorubicin when they are cultured in vitro or established as xenograft tumors in mice. The purpose of this study is to determine whether CREB3L1 expression in tumor cells of TNBC patients can be established as a biomarker to predict outcomes of doxorubicin-based chemotherapy. METHODS:We performed a retrospective analysis on breast core biopsy tissue samples taken from 18 TNBC patients before they were treated with doxorubicin-based chemotherapy. CREB3L1 expression in the cancer cells was analyzed by immunohistochemistry and quantified using the Immunoreactive Score (IRS). Outcomes of the chemotherapy were measured by the residual cancer burden (RCB) system. RESULTS:CREB3L1 expression levels in TNBC responsive to doxorubicin-based chemotherapy (RCB class 0-2) were significantly higher than that in resistant cancers (RCB class 3) (unpaired two-tailed t test, p = 0.0005; Statistical power 99.8 at 95% confidence level). All cancers expressing higher levels of CREB3L1 (IRS 4-12) responded to doxorubicin-based chemotherapy, whereas all cancers resisting the treatment expressed lower levels of CREB3L1 (IRS 0-3). CONCLUSIONS:These results suggest that CREB3L1 expression level may be used as a biomarker to identify TNBC patients who are more likely to benefit from doxorubicin-based chemotherapy.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Denard B,Jiang S,Peng Y,Ye J

doi

10.1186/s12885-018-4724-8

subject

Has Abstract

pub_date

2018-08-13 00:00:00

pages

813

issue

1

issn

1471-2407

pii

10.1186/s12885-018-4724-8

journal_volume

18

pub_type

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