Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients

Gago, Francisco E.; Tello, Olga; Diblasi, Ángela Magdalena; Ciocca, Daniel R.

doi:10.1016/s0960-0760(98)00140-x

Cited by 26 publications

(25 citation statements)

References 25 publications

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“…Despite these limitations, there have been several studies of assessing PR by immunohistochemistry in various settings in breast cancer. For example, three studies 15,31,32 assessed [33][34][35][36][37][38][39][40][41][42][43][44] Only seven [33][34][35]39,40,42,44 showed a significant relationship between PR status and clinical benefit. Of these positive studies, four 34,35,39,40 used frozen section immunohistochemistry, and the other three, which were done on archival tissue, used either KD 68 42 or noncommercial antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Of these positive studies, four 34,35,39,40 used frozen section immunohistochemistry, and the other three, which were done on archival tissue, used either KD 68 42 or noncommercial antibodies. 33,44 Similarly, four studies, 12,31,35,45 evaluated patients with advanced/metastatic disease, and three 12,31,35 showed a significant clinical benefit of hormonal therapy in patients with PRpositive tumors. All three studies employed the KD 68 antibody.…”

Section: Discussionmentioning

confidence: 99%

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Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

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Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays. However, most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor, but unfortunately no validated immunohistochemical assay exists for progesterone receptor. The purpose of this study was to develop and validate an immunohistochemical assay for progesterone receptor in breast cancer. The assay was based on monoclonal antibody 1294 (DakoCytomation) and slides were scored microscopically using the 'Allred score' on a scale of 0-8. The assay was compared to ligand-binding assay in 1235 breast cancers, and a subset (n ¼ 362) that received only hormonal therapy was used to define a cutoff for progesterone receptorpositive. Clinical utility was validated in an independent set of samples (n ¼ 423) from a clinical trial randomizing premenopausal breast cancer patients to tamoxifen þ oophorectomy vs observation following surgery. A cutoff of 42 (corresponding to 41% positive cells) dichotomized patients with significantly better or worse clinical outcome (P ¼ 0.0014). Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by ligand-binding assay in predicting clinical outcome. In the clinical trial, a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated (hazard ratios/P ¼ 0.656/0.060 and 0.479/0.005, respectively) and hormonally treated patients (hazard ratios/P ¼ 0.529/0.017 and 0.451/0.007, respectively). Positive progesterone receptor remained significant for improved disease-free and overall survival (hazard ratios/P ¼ 0.666/0.038 and 0.549/0.007, respectively) in multivariate analyses including the standard variables of tumor size, nodal status, treatment, histological grade, and HER-2/neu status. Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis. This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer. Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by ligand-binding assay.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

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“…Among 205 patients undergoing a variety of treatments, Gago et al (1998) observed a higher incidence of subsequent metastatic recurrences in the group of patients whose primary tumor had been Pgp + than in those with Pgp − tumors (27 vs 16% respectively). The prognostic association was statistically significant by univariate but not by multivariate analysis.…”

Section: Pgp/mdr1 Expression and Response To Treatmentmentioning

confidence: 97%

“…Eight studies on Pgp expression in untreated breast cancer used more than one antibody www.endocrinology.org 49 (Wishart 1990et al, De la Torre et al 1994, Decker et al 1995, Linn et al 1995, Wang et al 1997, Gago et al 1998, Yang et al 1999. Of these, six studies used two antibodies, and two (Linn et al 1995, Wang et al 1997) used three antibodies.…”

Section: Pgp/mdr1 Expression In Untreated Breast Cancer and Normal Timentioning

confidence: 99%

“…Of these, six studies used two antibodies, and two (Linn et al 1995, Wang et al 1997) used three antibodies. Different antibodies were used on separate samples, with one exception where two antibodies were used as a 'cocktail' (Gago et al 1998). Only four of the above papers report the results in a way that allowed us to calculate the detection rate when positivity is defined as staining with both of two antibodies: the pooled rate is 24% (or 30/124) (Wishart et al 1990, De la Torre et al 1994, Decker et al 1995, Wang et al 1997.…”

Section: Pgp/mdr1 Expression In Untreated Breast Cancer and Normal Timentioning

confidence: 99%

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ATP binding cassette transporters and drug resistance in breast cancer.

Leonessa¹,

Clarke²

2003

Endocrine-Related Cancer

233

178

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Resistance to chemotherapy is a critical issue in the management of breast cancer patients. The nature of clinical drug resistance is likely to be multifactorial. However, in the last decade considerable attention has been dedicated to the role played by membrane transporter proteins belonging to the ATP binding cassette protein superfamily, and in particular by the MDR1 product P-glycoprotein (Pgp) and the multidrug resistance protein (MRP1). Heterogeneity of results is a common feature of studies evaluating the expression and prognostic role of these proteins, due to both methodological and biological factors. Nonetheless, Pgp and MRP1 are detected in a significant proportion of untreated breast cancers (on average 40 and 50% respectively, by immunohistochemistry), without a clear and consistent association with cancer stage. Exposure to chemotherapy increases the expression of both proteins. In vitro studies on primary cultures of breast cancer cells obtained at surgery consistently show an association between Pgp (protein) or MDR1 (mRNA) expression and resistance to chemotherapy. However, the correlation with clinical drug resistance is not as well defined. A stronger association of Pgp/MDR1 with response rates has been observed when expression or an increase in expression are detected immediately following chemotherapy. Correlations with prognosis appear more evident in studies using immunohistochemistry, in adjuvant and neoadjuvant settings. Evidence of clinical reversal of drug resistance by verapamil suggests a functional role of Pgp in drug resistance, although the significance of the evidence is generally weakened by poor trial designs. Future studies should take into account the multifactorial nature of drug resistance in breast cancer and use standardized approaches with adequate controls. Expression studies should be complemented by well-designed trials of drug-resistance reversal using target-specific chemosensitizing agents, and relating the results to the levels of expression of the target proteins.

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Hsp27 as a Prognostic and Predictive Factor in Cancer

Ciocca¹,

Vargas–Roig²

2002

Small Stress Proteins

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Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients

Cited by 26 publications

References 25 publications

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

ATP binding cassette transporters and drug resistance in breast cancer.

Hsp27 as a Prognostic and Predictive Factor in Cancer

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