Determination Of Progesterone Receptors Research Articles

Evaluation of a hormone receptor‐positive ovarian carcinoma subtype with a favourable prognosis by determination of progesterone receptor and oestrogen receptor 1 mRNA expression in formalin‐fixed paraffin‐embedded tissue

In vitro and epidemiological studies indicate an essential role for progesterone in the aetiology and progression of ovarian carcinoma. The aim of this study was to examine the prognostic role of progesterone receptor (PR) protein and mRNA expression. PR expression was examined by immunohistochemistry (n=143) and kinetic reverse transcription-polymerase chain reaction (RT-PCR) from formalin-fixed and paraffin-embedded tissue (n=55). PR mRNA and protein expression correlated (P<0.0001). PR mRNA was a positive predictor for overall and progression-free survival (P=0.0005 and P<0.0001, respectively). Protein expression was also prognostic (P=0.015 and P=0.0011, respectively), whereas only PR mRNA retained its prognostic value on multivariate analysis (P=0.04). PR mRNA was still a positive prognostic marker among oestrogen receptor 1 (ESR1) mRNA-positive tumours (P=0.0007) and survival was best in patients with PR- and ESR1-positive phenotypes (P=0.0155 and P=0.0016, respectively). Expression of PR and ESR1 defines a subgroup of ovarian carcinomas with a favourable prognosis. PR and ESR1 mRNA expression analysis is a sensitive, quantitative and easy-to-perform high-throughput analytical tool for the identification of this subgroup and could be predictive in clinical trials focused on patients with potential benefit from hormonal treatment.

The Effect of Delay in Fixation, Different Fixatives, and Duration of Fixation in Estrogen and Progesterone Receptor Results in Breast Carcinoma

Accurate determination of estrogen receptor (ER) and progesterone receptor (PR) status in breast carcinoma is essential. Preanalytic variation may contribute to discordant results. Recently, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) made recommendations to normalize fixation for breast biomarkers. To evaluate this, a 4-cm invasive lobular carcinoma was processed according to ASCO/CAP guidelines. The remainder was stored fresh at 4°C for 4 days and cut into biopsy-sized pieces. Each was fixed in 10% formalin, Pen-Fix (Richard-Allan Scientific, Kalamazoo, MI), Bouin solution, Sakura Molecular Fixative (Sakura Tissue-Tek Xpress, Torrance, CA), zinc formalin, or 15% formaldehyde for times ranging between 1 and 168 hours. Immunohistochemical studies for ER and PR were performed and interpreted. After 4 days at 4°C, all samples showed no degradation or ER/PR staining differences, except 2 Bouin-fixed samples, in comparison with the patient's sample processed according to ASCO/CAP guidelines. In our study, the preanalytic variables of fixative type, fixation time, and 4 days of ischemic time did not affect immunohistochemical accuracy for ER/PR.

Quantitative Determination of Estrogen Receptor, Progesterone Receptor, and HER2 mRNA in Formalin-fixed Paraffin-embedded Tissue—A New Option for Predictive Biomarker Assessment in Breast Cancer

The development of optimized therapy strategies against malignant tumors is critically dependent on the assessment of tissue-based biomarkers in routine diagnostic tissue samples. We investigated a novel, fully automated, and xylene-free method for RNA isolation and biomarker determination using formalin-fixed paraffin-embedded (FFPE) tissue. The aim was to show that this approach is feasible and gives results that are comparable to the current gold standards. Expression of the breast cancer biomarkers ESR1, PGR, and HER2 was measured in a total of 501 FFPE tissue samples from 167 breast carcinomas, which had been stored for up to 21 years. Total RNA was extracted from tissue sections and biomarker expression was measured by kinetic RT-PCR (RT-kPCR). The results of the new method were compared with immunohistochemistry as the current gold standard.RNA was successfully isolated from all samples, with a mean yield of 1.4 μg/sample and fragment lengths of at least 150 bp in 99% of samples. RT-kPCR analysis of ESR1, PGR, and HER2 was possible in all samples. Comparing RT-kPCR results with standard IHC, we found a good concordance for ESR1 (agreement: 98.4%), PGR (84.4%), and HER2 (89.8%). We observed a low section-to-section variability of kPCR results for all 3 biomarkers (root of mean squared errors: 0.2 to 0.5 Ct values). The new approach is a reliable high-throughput instrument for standardized testing of biomarkers in clinical routine and for research studies on archived FFPE material up to 21 years old. For the assessment of ESR1, PGR, and HER2 the results are comparable to the current gold-standard.

Gene Expression Profiling for Breast Cancer Prognosis in Chinese Populations

To investigate a quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay different from 21-gene assay which can be used to prognosticate the risk of recurrence in patients with estrogen receptor (ER) positive, lymph node (LN) negative breast cancer. To accurately determine the relationship between the Recurrence Score (RS) derived from our assay and the risk of distant recurrence in Chinese patients with LN negative and positive breast cancer through the analysis of paraffin tissues. We obtained archival paraffin-embedded tissues from patients with invasive breast cancer and varying axillary lymph node involvement. QRT-PCR reaction was performed by using the method of SYBR Green I dye with primers. Expression of the 21-genes was converted to RS by a prespecified algorithm. We then assessed the probability of the test to accurately predict distant recurrence-free survival in this retrospective cohort. Ninety-three patients were eligible based on gene expression profiles. In our population, most breast cancer patients were premenopausal (82.6%), at early stage (93.6%) and ER positive (91.4%). Median follow-up was 65.9 months. The 5-year recurrence-free survival rate for the group was 58.8%. The concordance between the reverse transcription-PCR and immunohistochemical (IHC) measurement for ER, progesterone receptor (PgR), and HER-2 determinations was high and comparable. High RS was predictive of an elevated risk of relapse (p < 0.001). In subgroups of patients, RS had significantly predictive performance both in node-negative (p = 0.009) and node-positive patients (p = 0.038). Multivariable analysis showed that nodal status, adjuvant hormonal therapy and RS were significantly related to prognosis. RS category is a better predictor than the other risk assessment criteria or clinicopatholic features, with which we can determine more accurately the risks for recurrence of various patients. We have established an easy and economical QRT-PCR assay and validated in concordance with IHC measurements for ER, PgR, and HER-2. RS was associated with distant recurrence among Chinese patients with hormone receptor (HR) positive breast cancer. This study may promote the use of RS estimated from the expression of the 21-gene set for prognostication and routine clinical diagnostic application in Chinese populations.

Clinical and epidemiologic profile of breast cancer in Tanzania.

breast cancer is a highly heterogeneous disease globally. Public health prevention measures require an understanding of the burden of breast cancer and its risk factors. The purpose of this study was to describe the clinical, pathologic, and epidemiologic characteristics of breast cancer patients in Tanzania. data was abstracted from the medical records of all breast cancer patients attending Ocean Road Cancer Institute (ORCI) over a 2-year period from July 2007 to June 2009. Tumor tissue paraffin blocks were collected for all patients with available tissues for the determination of estrogen receptor (ER) and progesterone receptor (PR). Data for all patients was analyzed descriptively and by using unconditional logistic regression, by comparing early stage (ES), defined as stages I and II and late stage (LS), defined as stages III and IV patients to obtain odds ratios (ORs), 95% confidence intervals (CIs), and P-values. among the 488 patients, stage was determined for 356~patients, 90.7% of whom presented in LS. Of the 57 tumor tissues, 49.1% were ER-/PR-. Patients with ulceration (OR = 4.97; 95% CI= 1.07, 23.04; p=0.04) and peau d'orange (OR= 6.78; 95{\%} CI $=$ 1.48, 31.17; p=0.01) were more likely to present in LS rather than ES. Male breast cancer accounted for 2.9% of all breast cancers and inflammatory breast cancer (IBC) comprised 4.3-5.5% of cases based on registered t4d diagnosis or the criteria of IBC signs, if t4d was not reported in the medical records. most breast cancer patients in Tanzania are diagnosed at advanced disease stages with about half of the tumors being ER-/PR-. These data strongly support that reducing barriers to care, down-staging of disease at diagnosis, implementation of clinical guidelines for management of advanced cases, and palliative care are the four most essential factors that need to be addressed to reduce morbidity and mortality from breast cancer in Tanzania. Further research is needed to quantify the magnitude and molecular features of two relatively rare forms of breast cancer that may account for a greater proportion of the burden of breast cancer in Tanzania compared to the USA and Western Europe: male breast cancer and IBC.

Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect the accuracy, resulting in misclassification. Here, we investigated the association of microarray-based mRNA expression levels compared with immunohistochemistry. Microarray mRNA quantification of ER, PR, and HER2 was done by the developed TargetPrint test and compared with immunohistochemical assessment for breast tumors from 636 patients. Immunohistochemistry was done in a central laboratory and in an independent reference laboratory according to American Society of Clinical Oncology/College of American Pathologists guidelines for 100 cases. For HER2 immunohistochemistry 2+ cases, additional chromogenic in situ hybridization (CISH) was used to determine the final status. ER concordance between microarray and central immunohistochemistry was 93% [95% confidence interval (95% CI), 91-95%]. Only 4% of immunohistochemistry-positive samples were classified negative using microarray, whereas 18% of immunohistochemistry-negative samples showed a positive microarray ER status. Concordance for PR was 83% (95% CI, 80-86%) and 96% of all samples showed an identical classification of HER2 status by microarray and immunohistochemistry/CISH (95% CI, 94-98%). Nine percent of immunohistochemistry HER2-positive samples showed a negative microarray classification. Detailed review of 11 cases with discordant classifications by American Society of Clinical Oncology/College of American Pathologists and central immunohistochemistry indicated that microarray assessment was likely to add additional information in 5 cases. Microarray-based readout of ER, PR, and HER2 shows a high concordance with immunohistochemistry/CISH and provides an additional, objective, and quantitative assessment of tumor receptor status in breast cancer.

Her-2/neu gene overexpression in breast carcinoma and its association with clinicopathological characteristics of the disease.

To assess the frequency of Her-2/neu gene amplification in breast cancer and its association with clinicopathologic characteristics of the disease. Cross-sectional comparative study. Study was carried out at Surgical Unit I, Holy Family Hospital, Rawalpindi, from January 2005 to December 2006. A total of 50 patients diagnosed of having breast cancer on biopsy of breast lump were included in the study. All patients underwent mastectomy and samples were submitted to AFIP (Armed Forces Institute of Pathology, Rawalpindi) for histopathology and determination of estrogen and progesterone receptors and Her-2/neu gene amplification. Moreover, association of Her-2/neu amplification to other characteristics like tumour size, node involvement, histological grade and presence of estrogen and progesterone receptors were also studied. Out of 50 patients, 18 (36%) were positive for Her-2/neu overexpression. Among the various prognostic factors, age showed a statistically significant relation to Her-2/neu positivity (p=0.001). The Her-2/neu positive cancers were larger in size (mean size of 7.9 +/- 3.615 and 5.4 +/- 1.906 cm in Her-2/neu positive and negative cases respectively; p=0.002). Her-2/neu positive cases had statistically significant relation to number of involved lymph nodes (mean number of 9.9 and 4.4 lymph nodes in Her-2/neu positive and negative cases respectively; p=0.001). Tumour grade and nuclear grade had no statistically significant relation to Her-2/neu status (p=0.19 and 0.434 respectively). Both estrogen and progesterone receptors are inversely related to Her-2/neu positivity (p=0.028 and 0.006 respectively). The pathological and clinical characteristics of Her-2/neu positive and negative subsets differ, and Her-2/neu overexpression was associated with other poor prognostic factors of age, tumour size and number of nodes involved. There was an inverse relation of Her-2/neu status and hormone receptor.

RCL2, a New Fixative, Preserves Morphology and Nucleic Acid Integrity in Paraffin-Embedded Breast Carcinoma and Microdissected Breast Tumor Cells

Methacarn and RCL2, a new noncrosslinking fixative, were compared to formalin-fixed or frozen tissue samples of the same invasive breast carcinoma and were evaluated for their effects on tissue morphology and immunohistochemistry as well as DNA and RNA integrity. The histomorphology of methacarn- or RCL2-fixed paraffin-embedded tumors was similar to that observed with the matched formalin-fixed tissues. Immunohistochemistry using various antibodies showed comparable results with either fixative, leading to accurate breast tumor diagnosis and determination of estrogen and progesterone receptors, and HER2 status. Methacarn and RCL2 fixation preserved DNA integrity as demonstrated by successful amplification and sequencing of large DNA amplicons. Similarly, high-quality RNA could be extracted from methacarn- or RCL2-fixed paraffin-embedded MCF-7 cells, whole breast tumor tissues, or microdissected breast tumor cells, as assessed by electropherogram profiles and real-time reverse transcriptase-polymerase chain reaction quantification of various genes. Moreover, tissue morphology and RNA integrity were preserved after 8 months of storage. Altogether, these results indicate that methacarn, as previously shown, and RCL2, a promising new fixative, have great potential for performing both morphological and molecular analyses on the same fixed tissue sample, even after laser-capture microdissection, and can open new doors for investigating small target lesions such as premalignant breast lesions.

Immunohistochemical determination of estrogen and progesterone receptor positivity in uterine adenosarcoma

Background. Given the paucity of data regarding hormone dependency, it was the purpose of this study to screen for the presence of estrogen and progesterone receptors in uterine adenosarcoma (UAS). Methods. One hundred and five centers were asked to screen their files for uterine adenosarcomas. A immunohistochemical estrogen and progesterone receptor determination was performed. Results. Twenty-eight primary UAS were stained, including one cervical adenosarcoma. Sarcomatous overgrowth could be observed in eight. Furthermore, two cases of recurrent UAS, one only consisting of endometrial stromal sarcoma, were stained. UAS lacking sarcomatous overgrowth showed estrogen receptor positivity in 17/20 (85%) and 16/20 (80%) in the epithelial and sarcomatous component, respectively. Progesterone positivity was observed in 13/20 (65%) and 12/20 (60%) in the epithelial and sarcomatous component, respectively. In 18/20 (90%) of the cases, either the estrogen or the progesterone receptor stained positive in the sarcomatous component. UAS with sarcomatous overgrowth showed estrogen receptor positivity in 4/8 (50%) and 0/8 (0%) in the epithelial and sarcomatous component, respectively. Progesterone positivity was observed in 2/8 (25%) and 1/8 (12%) in the epithelial and sarcomatous component, respectively. The stromal component of both recurrent cases stained moderately positive for estrogen receptor whereas progesterone receptor was considered negative. Conclusion. The observation that the sarcomatous component of UAS without sarcomatous overgrowth frequently expresses hormone receptors might be of significant clinical importance.

Determination of progesterone receptor by chemiluminescent enzyme immunoassay

A new method of chemiluminescent enzyme immunoassay (CLEIA) was developed and the standard curve and regression equation for determination of progesterone receptor (PR) made. The luminosity of tissue samples was tested and PR level was calculated by the regression equation. Correlation analysis revealed that there was a linear relationship between different concentrations of the standard PR samples and the corresponding values of luminosity: Y=3748+463.77X, γ=0.9958. The values of the luminosity in 38 cases of tumor tissues were determined with the highest being 267.32 fmol/mg, the lowest 3.69 fmol/mg and the mean 78.53 fmol/mg. The new method of CLEIA was a stable, creditable, specific and sensitive assay for determination of PR.

Correlation of Immunocytochemical and Immunohistochemical Determination of Estrogen and Progesterone Receptors in Breast Cancer

To evaluate prospectively the degree of correlation between immunocytochemical (ICC) and immunohistochemical (IHC) determination of estrogen (ER) and progesterone receptors (PR) in breast cancer. Fine needle aspiration cytology (FNAC) of 101 primary breast cancers were immunostained for ER and PR. They were compared with similar determinations in formalin-fixed paraffin sections of biopsies from the same patients. In cases of discrepancy, the histologic result was considered the gold standard. For ER a cytohistologic correlation of 94%, with a sensitivity of 96.1% and specificity of 86.9%, was found. For PR the cytohistologic correlation was 71.2%, with a sensitivity of 65.7% and specificity of 83.8%. ICC determination of hormone receptors in routinely fixed smears obtained by FNAC is a simple method that correlates adequately with the results of IHC determinations, especially for ER.

Neoadjuvant tamoxifen for hormone-sensitive non-metastatic breast carcinomas in early postmenopausal women

BackgroundFrom 1984 to 1996, 1581 postmenopausal women aged 50–70 years old were treated at Institut Bergonié for an infiltrative non-metastatic breast carcinoma with a positive estrogen and/or progesterone receptor determination. Patients and methodsAmong them, 199 were treated with first line tamoxifen. Ninety-seven had operable disease (T2 >30 mm, T3, N0/1) and 102 had T4 tumours. ResultsAfter a mean treatment duration of 5.3 months, 89 T2 and T3 (92%) and 93 T4 (91%) were treated by surgery (conservative or not) with or without irradiation, or by irradiation alone. Conserving treatment levels were 53.6% and 44%, respectively. The other women were treated with either second-line chemotherapy or another hormonotherapy; the remaining patients continued regularly with tamoxifen. Overall survival is analysed with a 83 month median follow-up. ConclusionsA comparison between neoadjuvant endocrine therapy and surgery seems feasible to assess the concept of neoadjuvant hormonotherapy.

The importance of simultaneous determination of breast cancer biomarkers

It is shown that steroid hormone receptors by themselves are not sufficiently strong prognostic factors in management of breast cancer. For that reason, simultaneous consideration of different biomarkers seems to be more appropriate for clinical use, i.e. selections of patients with high/inter-mediate/low risk of disease outcome. However, the amount of tumor material available from breast carcinoma can preclude determination of estrogen- regulated biomarkers together with estrogen receptor and progesterone receptor. The aim of this study was to assess the possibility of estrogen receptor and progesterone receptor determination by a single-point instead of five-point biochemical method. Our results demonstrated that the correlation between measurements of estrogen and progesterone receptor contents obtained by the five-point and single-point assay in the total population was very high. Consequently, we could use the single-point assay instead of five-point assay for estrogen receptor and progesterone receptor determination, thus making possible determination of other molecular biomarkers from the same breast carcinoma.

Single-point versus five-point biochemical method for determination of estrogen and progesterone receptors

Receptors for estrogen and progesterone are accepted by international consensus as biomarkers of breast carcinoma responsiveness to endocrine therapy. Numerous current studies are aimed at consideration of importance of "the new generation" of estrogen-regulated biomarkers in treatment of breast cancer patients. Simultaneous knowledge of all these biomarkers may help in medical decision making. However, the amount of tumor material available from breast carcinoma can make impossible determination of estrogenregulated biomarkes together with estrogen and progesterone receptors. To assess whether we could replace our current five-point ligand binding assay for measurement of estrogen and progesterone receptors with a single- point ligand binding assay, we compared simultaneous measurements in same samples of breast carcinomas by both methods. A linear regression analysis shows that single-point assay can be confidently used instead of five-point assay. In addition, there were no variations over time in estrogen and progesterone receptors phenotypes, as well as in estrogen and progesterone receptors contents determined by single-point assay. Accordingly, the results clearly demonstrate the validity of intralaboratory quality control and give a possibility for the establishment of interlaboratory quality control of single-point ligand binding assay.

Computer-assisted immunocytochemical determination of breast cancer steroid receptors. Frozen sections vs paraffin sections

Previously we have demonstrated that determination of oestrogen (ER) and progesterone (PR) receptors by immunocytochemical assay (ICA) on frozen sections (FS) and cytological smears with image analysis is effective for evaluating steroid receptors. The aim of this study was to determine concordance between ER and PR assessed by ICA on FS and paraffin sections (PS) both evaluated by image analysis. There were 115 breast carcinomas selected. For all cases, ER and PR determination was performed on FS and PS. Computer-assisted image analysis was performed using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. Good correlation was demonstrated for both ER (r=0.759; concordance=83.4%) and PR (r=0.800; concordance=87.8%). The unexpected relatively low concordance for ER led to further investigations. We divided the 115 cases in two groups. The first group included specimens from our hospital; the second group specimens from suburban hospitals. In the first group there was better correlation for both ER (r=0.897) and PR (r=0.915) with a concordance of 91.5% and 93.6%, respectively. In the second group, correlation was worse for both ER (r=0.724) and PR (r=0.708), with a concordance of 77.9% and 83.9% respectively. From analysis of discordant cases we conclude that reduction in correlation and concordance with increased false negative cases in group 2 are probably due to delayed fixation. Our data suggest that ICA with automated image analysis is efficient in evaluating ER and PR on paraffin section only when the tumour samples are correctly fixed.

Histologic Grade and CD44 Are Independent Predictors of Axillary Lymph Node Invasion in Early (T1) Breast Cancer

Background: The detection rate of small, often subclinical breast cancers is increasing in affluent societies. Concomitantly, the demand for more conservative surgical approaches is also increasing among the women affected. Predictors of the absence of nodal invasion would spare many patients with early breast cancer the risks, costs and side effects of lymphadenectomy, and thus treatment with curative intent would be applied using really minimal surgery. Patients and Methods: We reviewed the records of 135 patients with unifocal invasive breast cancers, 2 cm or less in diameter, operated upon at ‘Fundación Tejerina-Centro de Patología de la Mama’, Madrid, Spain, between January 1993 and December 1997. Full clinical and pathological data were available for all of them, together with estrogen and progesterone receptor determinations, which had been routinely performed in 134 and 133 cases, respectively. Additionally, Ki67, c-erb-B2, p53, nm23, HSP27, HSP60 and CD44std expression was studied on archival, paraffin-embedded tumor material from these same patients by means of immunohistochemistry. Results: In the univariate analysis, only histologic grade 3 (p < 0.001), Ki67 expression in more than 10% of tumor cells (p = 0.005) and CD44std negativity (p = 0.004) were significantly associated with axillary node involvement. In multivariate analysis, histologic grade 3 and CD44std negativity retained statistical significance, and thus emerged as independent predictors of nodal invasion. The combination of both, furthermore, identified a subgroup in which the axillary nodes were invariably affected. Conclusion: Some pathological and molecular features of small breast cancers were able to predict nodal metastasis significantly. However, none, either alone nor combined, was able to exclude axillary node invasion completely.

Immunometric assays of ras and c-erbB-2/neu overexpression in breast cancer: a pilot study.

The expression of the ras and c-erbB2 oncoproteins (p21 and p185, respectively), together with estrogen receptor (ER) and progesterone receptor (PgR) determination, has been retrospectively analyzed in 68 primary breast carcinomas and in 19 normal breast tissue samples. The aims of this study were: a) to explore the association between ras and c-erbB2 expression; b) to evaluate the relationship between ras and c-erbB2 expression and both steroid receptor status and the classical clinical and pathological parameters; and c) to compare two different methods for p185 determination. p185 and p21 were measured by enzyme immunoassay (EIA); p185 was also determined by Western blotting (WB); ER and PgR were assayed by radioligand binding assay. The highest value of p185 in benign breast lesions was used as the threshold to distinguish between positive and negative samples. With this threshold the c-erbB2 oncoprotein was overexpressed in 41.2% (with EIA) and in 50% (with WB) of cancer samples. The concordance rate between the two methods was 79.4. No significant association was found between p21 and p185 levels either in cancer or in normal breast tissue samples. Increasing levels of tumor p21 were associated with a shorter time to recurrence and overall survival. Increasing levels of p185 were associated with a significantly shorter time to recurrence (p185 EIA: p = 0.04, p185 WB: p = 0.029) and overall survival (p185 EIA: p = 0.04, p185 WB: p = 0.029).

Oestrogen-receptor status in management of breast cancer in UK

In patients with breast cancer, oestrogen receptor (ER) status is recognised as a powerful predictor of response to endocrine therapy in both advanced disease 1 Bezwoda WR Esser JD Dansey R Kessel I Rad MM Lange M The value of estrogen and progesterone receptor determinations in advanced breast cancer. Cancer. 1991; 68: 867-872 Crossref PubMed Scopus (79) Google Scholar and in the adjuvant setting. 2 Early Breast Cancer Trialists' GroupSystemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000. Lancet. 1992; 339: 1-15 PubMed Google Scholar A study 3 Wishart GC Harnett AN Purushotham AD The availability of oestrogen receptor (ER) status strongly influences recommendations for adjuvant systemic therapy in higher risk breast cancer patients. Breast. 1997; 6: 237 Summary Full Text PDF Google Scholar has shown that the availability of ER status strongly influences recommendations for adjuvant systemic therapy, including the selection of appropriate clinical trials for individual patients in keeping with a move towards more individualised treatment of women with breast cancer. 4 Elledge ME Osborne CK Oestrogen receptors and breast cancer. BMJ. 1997; 314: 1843-1844 Crossref PubMed Google Scholar We aimed to assess the importance, use, and availability of this prognostic marker in breast cancer units in the UK.

Evaluation of a displacement assay with tamoxifen as prognostic indicator in breast-cancer patients with estrogen-receptor-positive tumors.

A displacement assay with tamoxifen, based on the relative binding affinity of tamoxifen and estradiol for the estrogen receptor (ER), was proposed in 1990 as prognostic indicator for breast-cancer patients. Validation of its predictive results in relation to the outcome of 73 patients with ER+ tumors is analyzed. ER, progesterone receptor (PgR) determinations and other conventional prognostic factors in relation to the displacement assay, were considered. Displacement assay results allowed ER+ tumors to be grouped as displaceable (D) or weakly displaceable (WD), with the implication that D tumors should respond better to tamoxifen (Tam) administration. Survival and disease-free interval curves showed highly significant differences between patients with ER+ D and ER+ WD tumors. For survival, including all tumor stages, 73.9% of patients were alive at 9 years after surgery in the group with D tumors and 37.0% in the group with WD tumors (p < 0.005); relative contribution of the different stages is analyzed. Addition of axillary-node number increased the prognostic significance of displacement categories for survival and disease-free interval. PgR determination as another ER functional expression failed to show significant differences for survival and disease-free interval between ER+ PgR+ and ER+ PgR- tumors. Thus, results from the displacement assay and from PgR determinations reflect 2 independent ER functional expressions. Displacement assay data appear as reliable prognostic indicators of breast-cancer outcome, and contribute to more appropriate treatment decisions in this pathology.

Cathepsin D versus other prognostic factors in breast cancer. Results and controversies of a multicenter study on 2575 cases.

The aim of this study was the survey of cathepsin D determination in a large group of patients enrolled at several centers, under the coordination of the Italian Committee for Quality Control in the Oncological Laboratory. Cathepsin D was measured with the same methodology, under control of an intra and interlaboratory quality control program, in order to verify the comparability of cathepsin D results from different institutions and to analyze the frequency of cathepsin D positive cases in subgroups of patients stratified according to other prognostic parameters. This retrospective study included 2575 patients with primary breast cancer evaluated in 10 institutions. Cytosol from tumor tissue was the substrate for biochemical cathepsin D, estrogen receptor and progesterone receptor determination, with an interlaboratory quality control survey provided by the E.O.R.T.C. Receptor Group and the Italian Committee for Quality Control in the Oncological Laboratory. The results of the present study can be summarized as follows: 1) Cathepsin D is independent of menopausal status; 2) In spite of standardization of tissue handling and assay methods, different results may be obtained by different institutions. It is therefore essential that each laboratory calculates its own positive/negative cutoff values prior to any routine clinical use of the parameter. This should be a serious consideration when a multicenter study is planned.