Open AccessFOXA 1 levels are decreased in pleural breast cancer metastases after adjuvant endocrine therapy, and this is associated with poor outcome
Author(s) -
Schrijver Willemijne,
Schuurman Karianne,
Rossum Annelot,
Droog Marjolein,
Jeronimo Carmen,
Salta Sofia,
Henrique Rui,
Wesseling Jelle,
Moelans Cathy,
Linn Sabine C.,
Heuvel Michel,
Diest Paul,
Zwart Wilbert
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12353
Subject(s) - breast cancer , medicine , tamoxifen , oncology , metastatic breast cancer , estrogen receptor , endocrine system , cancer , metastasis , cancer research , hormone
Estrogen receptor‐alpha ( ER α)‐positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ER α activity requires the functional involvement of pioneer factors FOXA 1 and GATA 3, which enable ER α–chromatin binding and are crucial for ER α‐driven cell proliferation. FOXA 1 was found increased in metastatic breast cancers in relation to the primary tumor, but a comprehensive clinical assessment thereof, in relation to different metastatic sites and endocrine therapy usage, is currently lacking. Prior cell line‐based reports, however, have revealed that FOXA 1 is required for tamoxifen‐resistant tumor cell proliferation. We studied expression levels of ER α, GATA 3, and FOXA 1 by immunohistochemistry in samples from both primary tumors and various metastatic sites. For all factors, expression levels varied between the metastatic sites. For pleural metastases, strong variation was found in FOXA 1 and GATA 3 levels. Although GATA 3 levels remained unaltered between primary breast cancer and pleural metastases, FOXA 1 levels were reduced exclusively in metastases of patients who received endocrine therapies in the adjuvant setting, even though ER α was still expressed. Importantly, decreased FOXA 1 levels in pleural metastases correlated with hormone irresponsiveness in the palliative setting, while no such correlation was found for GATA 3. With this, we show divergent clinical correlations of the two ER α pioneer factors FOXA 1 and GATA 3 in metastatic breast cancer, where endocrine therapy resistance was associated with decreased FOXA 1 levels in pleural metastases.