Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer. 1995

S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
Academic Department of Biochemistry, Royal Marsden Hospital, London, England.

Changes in estrogen receptor (ER) expression and function may explain the development of tamoxifen resistance in breast cancer. ER expression was measured by an immunohistochemical assay, validated for use in tamoxifen-treated tumors against a biochemical enzyme immunoassay, in 72 paired biopsies taken before treatment and at progression or relapse on tamoxifen. Progesterone receptor (PgR) and pS2 gene expression were also measured immunohistochemically as an indicator of ER function. Overall the frequency of ER expression was reduced from 37 of 72 (51%) pretamoxifen to 21 of 72 (29%) at progression or relapse, with a significant reduction in the quantitative level of ER (P < 0.0001; Wilcoxon signed rank sum test). Tumors treated with primary tamoxifen that responded but then developed acquired resistance frequently remained ER positive (ER+) at relapse: 16 of 18 (89%) were ER+ pretamoxifen (75% of these expressed either PgR or pS2) and 11 of 18 (61%) were ER+ at relapse (82% continued to express PgR or pS2). In contrast, only 3 of 20 (15%) tumors that progressed on primary tamoxifen with de novo resistance were ER+ pretamoxifen, and all tumors were ER- at progression. At progression, 6 of 20 (30%) of these tumors expressed high levels of PgR (mean H-score, 98) and/or pS2 (mean, 50% cells positive), despite being ER-. In tumors that recurred during adjuvant tamoxifen therapy, including locoregional and metastatic lesions, ER expression was significantly reduced from 18 of 34 (53%) in the original primary tumor to 10 of 34 (29%) at relapse (P = 0.002). PgR expression was likewise significantly reduced in this group (P = 0.001). This study confirms that expression of a functional ER in breast cancer is a strong predictor for primary response to tamoxifen. Although ER was reduced in tamoxifen-resistant tumors overall, the development of acquired resistance was associated with maintained ER expression and function in many tumors, whereas de novo resistance remained related to lack of ER expression. Recurrence during adjuvant tamoxifen was associated with development of an ER/PgR-negative phenotype in some tumors. These data imply that separate mechanisms of resistance may occur in these different clinical subgroups.

UI MeSH Term Description Entries
D007118 Immunoassay A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. Immunochromatographic Assay,Assay, Immunochromatographic,Assays, Immunochromatographic,Immunoassays,Immunochromatographic Assays
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D009364 Neoplasm Recurrence, Local The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site. Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D011960 Receptors, Estrogen Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D011980 Receptors, Progesterone Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives. Progesterone Receptors,Progestin Receptor,Progestin Receptors,Receptor, Progesterone,Receptors, Progestin,Progesterone Receptor,Receptor, Progestin
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005260 Female Females

Related Publications

S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
January 1997, Acta cytologica,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
January 1995, Cancer research,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
January 1994, Cancer research,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
November 1999, Cancer research,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
September 2005, Journal of the National Cancer Institute,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
January 2016, Journal of medicinal chemistry,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
June 1996, Medicina clinica,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
January 1998, Japanese journal of cancer research : Gann,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
May 1981, Cancer research,
S R Johnston, and G Saccani-Jotti, and I E Smith, and J Salter, and J Newby, and M Coppen, and S R Ebbs, and M Dowsett
July 1999, Breast cancer research and treatment,
Copied contents to your clipboard!