Abstract
IntroductionBcl-2 antanogene-1 (Bag-1) binds the anti-apoptotic mediator Bcl-2, and enhances its activity. Bcl-2 and Bag-1 are associated with chemotherapy resistance in cancer cells. Drugs that target Bcl-2 are currently in clinical development. The purpose of the present study was to examine expression patterns of Bag-1 in a large cohort of breast tumors and to assess the association with Bcl-2, estrogen receptor, progesterone receptor and Her2/neu, and other clinical/pathological variables.MethodsTissue microarrays containing primary specimens from 638 patients with 10-year follow-up were employed, and the expression of Bag-1, Bcl-2, estrogen receptor, progesterone receptor and Her2/neu was assessed using our automated quantitative analysis method. We used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and we measured biomarker expression within the mask using Cy5 conjugated antibodies.ResultsHigh Bcl-2 expression was associated with improved survival in the entire cohort and in the node-positive subset (P = 0.008 and P = 0.002, respectively). High Bag-1 expression was associated with improved survival in the node-positive subset (P = 0.006). On multivariable analysis, neither Bcl-2 nor Bag-1 retained their independence as prognostic markers. Strong associations were found between Bag-1, Bcl-2, estrogen receptor and progesterone receptor.ConclusionBag-1 and Bcl-2 expression in breast tumors is associated with improved outcome and steroid receptor positivity. Evaluation of Bcl-2 and Bag-1 expression in breast cancer may identify a subset of patients with a favorable prognosis, who might not benefit from chemotherapy or who might benefit from Bcl-2 targeting agents in addition to antihormonal therapy.
Highlights
Introduction Bcl2 antanogene-1 (Bag-1) binds the antiapoptotic mediator Bcl-2, and enhances its activity
Neither Bcl-2 nor Bcl-2 antanogene-1 (Bag-1) retained their independence as prognostic markers
Strong associations were found between Bag-1, Bcl-2, estrogen receptor and progesterone receptor
Summary
Introduction Bcl2 antanogene-1 (Bag-1) binds the antiapoptotic mediator Bcl-2, and enhances its activity. The purpose of the present study was to examine expression patterns of Bag-1 in a large cohort of breast tumors and to assess the association with Bcl-2, estrogen receptor, progesterone receptor and Her2/neu, and other clinical/ pathological variables. Over 40,000 women are expected to die from metastatic disease in 2007 [1]; adjuvant systemic therapy is given for early-stage disease to decrease the risk of death from breast cancer. It is well established that adjuvant chemotherapy decreases the risk of recurrence in node-positive patients [2], yet older studies showed that there is a subset of node-positive breast cancer patients, those with estrogen receptor (ER)-positive tumors, who survive with tamoxifen alone [3]. There is great need to identify new prognostic markers that will assist in patient selection for adjuvant
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