The relationship between tumour NF-kB expression, hormone status and survival in primary invasive breast cancer.

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Abstract Abstract #4041 Breast cancer is one of the most common and lethal malignancies in the UK. Conventionally, prognosis is based on hormone status, tumours size, grade and lymph node involvement. We have recently observed that NF-kB expression and activation was associated with progesterone receptor (PR) expression irrespective of oestrogen receptor (ER) status in primary invasive breast cancer (Tannahill et al., unpublished observations). The aim of the present study was to examine the relationship between NF-kB, PR and survival in a selected cohort of ER positive tamoxifen treated primary invasive breast cancer.
 Immunohistochemistry was performed on 372 breast tumours, with full clinicopathological characteristics. Antibodies were directed total NF-kB and NF-kB phosphorylated at serine 536 (phospho NF-kB). Two observers independently scored expression using the weighted histoscore technique, and grouped expression as tertiles. There was a minimum follow-up period of 4.9 years and a median follow-up of 6.8 years. During follow-up 104 patients died, 65 of which died of their disease, 96 patients recurred, 70 of which was while on tamoxifen.
 Nuclear NF-kB, either total or phosphorylated, expression was not associated with recurrence or survival. However, when the cohort was subdivided into PR positive (n=220) and PR negative tumours (n=140), increased nuclear phospho NF-kB expression was associated with increased recurrence (p<0.05) and increased recurrence on tamoxifen therapy (p<0.05) in PR positive tumours. In contrast, increased nuclear phospho NF-kB expression was associated with decreased recurrence (p<0.05) and decreased recurrence on tamoxifen therapy (p<0.05) in PR negative tumours.
 The results of the present study suggest that the effect of nuclear expression of phospho NF-kb on outcome in ER positive primary invasive breast cancer is dependent on PR status. The study highlights the importance of patient selection for the evaluation of the use of NF-kb inhibitors in patients with breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4041.