The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen

Abstract

Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer. Cancer 68:867-872,1991. HE UTILITY of estrogen receptor (ER) level estimation T as a predictor for hormone response in patients with advanced breast cancer has been described in several investigations .l-8 Most studies characterized tumors as being either ER positive or ER negative according to an arbitrarily defined value of estrogen binding. Quantitation of estrogen binding, however, shows the receptor values extend over a wide range and show a continuous distribution. It is thus preferable to speak of receptor-poor and receptor-rich tumors' rather than ER-negative and ER-From the Breast Clinic, Departments of *Medicine (Haematology/ Oncology), ?Nuclear Medicine, $Radiation Therapy, and §Surgery,

Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumors: being younger and getting less benefit from adjuvant tamoxifen treatment

“…ER+/PgR¡ and ER¡/PgR+ phenotypes might show an intermediate response rate to endocrine therapy. In a locally advanced or metastatic setting, the response rate of ER¡/PgR+ tumors to hormonal therapy was lower than that of ER+/PgR+ tumors (Bezwoda et al 1991;Osborne 1998b). In the adjuvant setting, however, there were few published evidences regarding ER¡/PgR+ tumors.…”

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions

“…Today, i.e. about 25 years later, the same proportions of breast cancer patients are reported to respond or not to respond to endocrine therapy (Bezdowa et al 1991;Harris et al 1997;Jozan et al 1991). This means that it is not the improvement of ER and PgR determination that will increase the accuracy of the predictive value associated with this determination in relation to the response to endocrine treatment, but another manner of considering the notion of breast cancer steroid hormone sensitivity.…”

“…Jensen and DeSombre (1993) report that, as the biochemical and immunohistochemical methods for the measurement of receptor proteins became more sensitive, it became evident that most breast cancers are heterogeneous and contain a mixture of ER-positive (ER + ), ER ) , and PgR-rich or PgR-poor. While it is well known that ER determination is of critical importance as a predictive factor for response to endocrine treatment (Bezdowa et al 1991;Harris et al 1997;Jozan et al 1991), the fact remains that about 40% of patients with ER-rich cancers show no objective remission following some type of endocrine therapy and that about 10% of ER-poor breast cancer patients will respond objectively to such therapies. PgR status must be determined in addition to ER status because PgR is known to be produced by oestrogen action in many female reproductive tissues (Jensen and DeSombre 1993).…”

Characterization of DNA-binding proteins as clinically relevant biomarkers of breast cancer behavior.

“…Currently, tamoxifen is the most commonly used endocrine therapy for breast cancers that are ER and/or PR positive. Fifty to eighty percent of these tumors respond to tamoxifen, while only 5-10% of ER-/PR-tumors respond [65][66][67][68]. Tamoxifen is a selective estrogen receptor modulator (SERM) and acts as an inhibitor of growth and proliferation of breast cancer cells by competitive antagonism of ER [69].…”

“…[247][248][249][250][251][252][253][254][255][256][257][258][259][260][261], PAI-311/a.a. [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] PAI-310 which may block binding of the receptor to e 2 p]ERE ( Figure 14). Figure 14 also shows that ERE-BP did not supershift in the presence of anti-ERp antibodies.…”