ER-negative breast cancer

Eisen SF, Brown HA (2002) Selective estrogen receptor (ER) modulators differentially regulate phospholipase D catalytic activity in ER-negative breast cancer cells. Mol Pharmacol 62(4) 911-920... 

A summary of the different prognostic markers for human cancers mentioned earlier is given in Table 4. It should be remembered that for many of these markers, results are still preliminary. Apart from ER and PR for breast cancer, none are in routine use. However, uPA is a potential prognostic marker for axillary node-negative breast cancer. 

In 2004, Liu et al. made an effort to incorporate estradiol into C-2, 7, and 10 positions in Taxol to target the drug to estrogen receptor (ER) positive breast cancer. For C-2 and C-7 conjugates, no satisfactory results were obtained for either activity or selectivity. But a 7-epi-lO-conjugated taxoid (119) did exhibit some selectivity between ER-positive and negative cancer cells, and ER-(3 (MDA-MB-231 cell) and ER-a expressing (MCF-7) cancer cells. " ... 

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004 351(27) 2817-26. 

The presence of estrogen receptors (ER) in biopsies of breast cancers is a good predictor of responsiveness to tamoxifen therapy 60% of women with ER-positive tumors will have a remission, as opposed to fewer than 10% with ER-negative tumors. Overall, 35 to 40% of women with breast cancer will respond to some degree, with antitumor effects lasting an average of 9 to 12 months. Complete remissions may occur in 10 to 15% of patients and may last several months to a few years. Therapy should be continued for at least 6 weeks to establish efficacy. 

Microarray analyses of breast cancer have identified unique gene expression profiles associated with patient survival. Sorlie et al. (23) found the expression profiles to distinguish ER-i- from ER- tumors with distinct outcomes in a cohort with locally advanced breast cancer treated with primary chemotherapy. Van t Veer et al. (18) established a 70-gene signature to predict metastatic potential in an untreated, node-negative cohort. Sotiriou et al. (24) showed the concordance with these previous analyses in node-positive and node-negative patients with the majority receiving adjuvant treatment. 

Most steroid-sensitive cancers express specific cell surface receptors. Prednisone-sensitive lymphomas, estrogen-sensitive breast cancers, and prostatic cancers express specific receptors for corticosteroids, estrogens, and androgens, respectively. It is now possible to assay tumor specimens for steroid receptor content and to identify which individual patients are likely to benefit from hormonal therapy. Measurement of the estrogen receptor (ER) and progesterone receptor (PR) proteins in breast cancer tissue is now standard clinical practice. ER or PR positivity predicts response to hormonal therapy, whereas patients whose tumors are ER-negative generally fail to respond to such treatment. 

Breast cancer cytosols Immunoassay Overexpressed in younger patients with early-stage disease, small ER - positive, low S-phase, low-cellularity diploid tumors Associated with a longer DFS and OSc Independent indicator of increased DFS for all patients as well as node-positive, ER-negative Favorable prognosis [269]... 

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