Assessment Of Hormone Receptor Status Research Articles

Percutaneous CT-Guided Bone Lesion Biopsy for Confirmation of Bone Metastases in Patients with Breast Cancer.

We aimed to determine diagnostic accuracy of CT-guided bone lesion biopsy for the confirmation of bone metastases in patients with breast cancer and assessment of hormone receptor status in metastatic tissue. A total of 56 female patients with breast cancer that underwent CT-guided biopsy of suspected bone metastasis were enrolled in this retrospective study. Three different techniques were employed to obtain samples from various sites of skeleton. Collectively, 11 true negative and 3 false negative findings were revealed. The sensitivity of CT-guided biopsy for diagnosing bone metastases was 93.6%, specificity was 100% and accuracy was 94.8%. Discordance in progesterone receptor status and complete concordance in estrogen receptor status was observed. Based on our single-center experience, bone metastasis biopsy should be routinely performed in patients with breast cancer and suspicious bone lesions, due to the impact on further treatment.

Radiomic Signatures Derived from Hybrid Contrast-Enhanced Ultrasound Images (CEUS) for the Assessment of Histological Characteristics of Breast Cancer: A Pilot Study.

Simple SummaryThe hybrid images obtained at the CEUS present an overlap of the tumor in grayscale over the enhancement pattern, which allows an appropriate evaluation of the entire lesion without including in the analysis the peritumoral area. We hypothesized that the spatial heterogeneity of tissue enhancement differs depending on histological characteristics. Therefore, the aim of this study was to evaluate the diagnostic performance of radiomic features extracted from standardized hybrid CEUS data for the assessment of hormone receptor status, HER2 status, tumor grade and Ki-67 in patients with primary breast cancer. The clinical benefit of this study would be to use CEUS and bioinformatics tools for improved biopsy planning or even guiding treatment decisions.The purpose of this study was to evaluate the diagnostic performance of radiomic features extracted from standardized hybrid contrast-enhanced ultrasound (CEUS) data for the assessment of hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, tumor grade and Ki-67 in patients with primary breast cancer. Methods: This prospective study included 72 patients with biopsy-proven breast cancer who underwent CEUS examinations between October 2020 and September 2021. Results: A radiomic analysis found the WavEnHH_s_4 parameter as an independent predictor associated with the HER2+ status with 76.92% sensitivity, and 64.41% specificity and a prediction model that could differentiate between the HER2 entities with 76.92% sensitivity and 84.75% specificity. The RWavEnLH_s-4 parameter was an independent predictor for estrogen receptor (ER) status with 55.93% sensitivity and 84.62% specificity, while a prediction model (RPerc01, RPerc10 and RWavEnLH_s_4) could differentiate between the progesterone receptor (PR) status with 44.74% sensitivity and 88.24% specificity. No texture parameter showed statistically significant results at the univariate analysis when comparing the Nottingham grade and the Ki-67 status. Conclusion: Our preliminary data indicate a potential that hybrid CEUS radiomic features allow the discrimination between breast cancers of different receptor and HER2 statuses with high specificity. Hybrid CEUS radiomic features might have the potential to provide a noninvasive, easily accessible and contrast-agent-safe method to assess tumor biology before and during treatment.

Risk of non-Hodgkin lymphoma in breast cancer survivors: a nationwide cohort study

Several studies have suggested that estrogens have a protective function against lymphomagenesis. The treatment of breast cancer is driven by subtype classification, and the assessment of hormone receptor status is important for treatment selection. Thus, we evaluated the association between breast cancer and the incidence of NHL. We conducted a retrospective cohort study using a population-based nationwide registry in South Korea. We selected all women with newly diagnosed breast cancer between January 1st, 2002 and December 31st, 2016 who received curative treatment (N = 84,969) and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). Incident breast cancer (time-varying exposure) was the exposure and development of any type of NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mature T/NK-cell lymphomas, anaplastic large cell lymphoma (ALCL), and unspecified types of NHL, was the outcome. During follow-up, 1564 incident cases of NHL occurred. The fully adjusted Hazard Ratio (HR) for NHL associated with the development of breast cancer was 1.64 (95% CI = 1.34–2.00) after adjusting for body mass index, alcohol intake, physical activity, smoking, income, and comorbidity. The adjusted HR for NHL was much higher in participants who were aged <50 years and who received hormone therapy (either tamoxifen or aromatase inhibitors) than in those ≥50 years or who did not receive hormone therapy, respectively. The development of breast cancer was associated with a significantly increased risk of NHL, particularly follicular lymphoma and mature T/NK-cell lymphoma. In particular, the risk of NHL was higher in patients receiving hormone therapy and in younger patients.

Assessment of the receptor status in primary breast cancer with synchronous loco regional metastases: prognostic and clinical role?

Background. Assessment of hormone receptor status plays a crucial role in treatment of patients with breast cancer. currently, clinicians are limited to determining the expression status of estrogen receptor (ER), progesterone receptor (pR) and HER2 only in primary breast cancer tissues, even in the presence of regional metastases.The purpose of the study was to review available data on heterogeneity of ER, pR and HER2/neu expressions in primary breast cancer and regional metastases.Material and methods. We analyzed publications available from pubmed, medline etc. using the keywords «discordance», «breast cancer», «locally advanced», «regional lymph nodes», «ER», «pR», and «HER2».Results. The clinical and prognostic role in assessing the heterogeneity of the receptor status of primary tumors and synchronous regional metastases, as well as the effect of detected discordance on treatment tactics was assessed.Conclusion. Data on the frequency of discordance in hormone receptor status between primary and metastatic breast cancer tumors and its effect on the further prognosis in breast cancer are still contradictory. However, the fact of the presence of such heterogeneity suggests that some patients with affected lymph nodes will have significant benefits from determining the status of steroid hormones and HER2 not only in the primary tumor, but also in the lymph nodes, since it will open up new opportunities for subsequent targeted therapy.

A plea for appraisal and appreciation of immunohistochemistry in the assessment of prognostic and predictive markers in invasive breast cancer

This viewpoint is a personal reflection on the values and merits of immunohistochemistry in current breast cancer diagnosis. Immunohistochemistry is a validated mainstay in molecular subtyping of invasive breast cancer. Immunohistochemical assessment of hormone receptor status and HER2 expression is used to determine the clinico-pathological surrogate of breast cancer intrinsic subtypes, which guide neoadjuvant and adjuvant therapy. The advent of genomic prognostic signatures and qualitative mRNA-based assays makes some clinicians and researchers wonder whether immunohistochemistry should be abandoned. However, the perils and pitfalls of these mRNA-based tests cannot be neglected. This viewpoint offers a brief overview of quality issues in immunohistochemistry and qPCR, as well as a concise summary of currently available evidence on the correlation of immunohistochemistry and mRNA-based testing for prognostic and predictive markers in invasive breast cancer. We strongly advocate the use of immunohistochemistry as it integrates valuable spatial information with quantification of protein expression.

Impact of oestrogen and progesterone receptor expression in the cancer cells and myometrium on survival of patients with endometrial cancer

Loss of oestrogen receptor (ER) and progesterone receptor (PR) expression in endometrial cancer cells indicates poor prognosis. The aim of this study was to determine the correlation of ER and PR expression in cancer cells and the surrounding myometrium with the disease progression. Immunohistochemical expression of ER and PR was detected in cancer and myometrial cells of patients with EC. ER was detected in 65.2% of cancer cells and in 88.4% of myometrial cells. PR was detected in 59.4% of cancer cells and in 84.1% of myometrial cells. The 5-year overall survival (OS) was 76.8%. Patients with ER and PR negative EC had a shorter period until recurrence (p = .013 and .043) and shorter OS (p = .011 and .066) than those with ER and PR positive cancer. Negative ER and PR status in EC has an impact on recurrence and poor OS. The status of hormone receptors in myometrium may be useful in disease prognosis.Impact StatementThe status of hormone receptors in endometrial cancer has been the subject of numerous studies and loss of hormone receptors indicates higher tumor grade and higher clinical stage, lympho-vascular space invasion and deeper myometrial invasion. Although, the communication between the endometrium and myometrium is crucial under physiological conditions, the status of hormone receptors in the myometrium and its significance in cancer progression is poorly studied.Our results showed that loss of ER in the myometrium indicate poor prognosis. The assessment of hormone receptor status in myometrium might be useful in predicting the course of the disease. Results of our research support the theory that stromal and myometrial cells may contribute to tumorigenesis in endometrial cancer.Better understanding of ER/PR expression in myometrial cells is needed, and our research opens new possibilities for identification of key pathways and new potential target molecules in EC prognosis and treatment. It is probable that future classification of endometrial cancer will rely on molecular sub-typing, where the status of hormone receptors in the myometrium might play an important role.

Abstract P3-05-08: Discordance in hormone receptor (HR) assessment by IHC and RT-PCR in an estrogen receptor (ER) low-positive group (1-10% positive cells): Does accurate assessment of HR status require dual testing?

Abstract Background: Accurate determination of hormone receptor (ER/PR) and HER2 status is critical for making treatment (Tx) decisions in early stage breast cancer (EBC) patients (pts). ASCO/CAP guidelines categorize pts with &amp;gt;1% ER/PR staining as ‘positive’ for HR expression. A formal interaction between quantitative ER expression by RT-PCR and tamoxifen response was demonstrated in NSABP B-14 (Kim C, JCO, 2011). Prognosis and Tx decisions depend on the status of ER expression and pts with ER(-) disease have a worse prognosis. A comparative study to evaluate ASCO/CAP cutoffs for ER protein expression and prospectively validated ER mRNA expression by RT-PCR was undertaken in consecutive EBC pts with either negative or low-positive ER by IHC from a single institution. Methods: Consecutive EBC pts with IHC defined ER(-) (&amp;lt;1% positive cells) or ER low-positive (1-10% positive cells; by ASCO/CAP guidelines) were identified at New York University School of Medicine. ER, PR and HER2 protein assessment used standard IHC methods (SP1, 1E2, 4B5, Ventana). ER, PR and HER2 mRNA assessment used the Oncotype DX® 21-gene assay, reference-normalized expression measurements ranged from 0 to 15, where each 1-unit increase reflects about a two-fold increase in RNA. The validated thresholds for positivity for the three markers were used: ER, 6.5, PR, 5.5 and HER2, 11.5. Descriptive statistics were calculated for baseline characteristics, and two-way classification tables were produced for ER by IHC versus RT-PCR. Results: Of 140 IHC evaluable samples, 106 (76%) were ER(-), 34 (24%) were ER low-positive, 116 (83%) PR(-), and 24 (17%) PR+. Pts included showed: 69.3% ≥50 yrs; 83.6% had poor differentiation; 31.2% had ≥1 positive nodes; 34.3% were ≥ 2.0cm. 37 pts (26.4%) were HER2+ by IHC or FISH. The cross classification of ER status by RT-PCR versus IHC is in the Table. For IHC ER(-) cases there was a 93.3% percent negative agreement (PNA) between IHC and RT-PCR. For IHC ER low-positive cases the percent positive agreement (PPA) was 38.2% between IHC and RT-PCR. ER expression (CT units) ranged from 2.8 to 8.3 for IHC negative cases and 3.4 to 9.2 for IHC low-positive cases. Conclusions: The status of ER, PR and HER2 is critical for Tx decision making in pts with EBC. In this cohort of ER(-) or low-positive expressing EBC cases there was high agreement between IHC and RT-PCR for negative ER expression (93% PNA); however, only 40% of ER- low-positive (1-10%) cases by IHC were positive by RT-PCR. While many of the discordant cases were near the RT-PCR cutpoint of 6.5, about 10% of the discordances were either strongly ER+ or strongly ER(-) by RT-PCR suggesting misclassification by central IHC. Thus, in many IHC ER- low-positive cases there may be little or no benefit from the addition of hormonal therapy. Accurate assessment of ER is critically important to ensure the best Tx and these findings indicate that dual testing of low-positive ER by IHC merits consideration and additional study. ER StatusIHCRT-PCRNegativeLow-positiveTotalNegative99 (93.3%)21 (61.7%)120 (85.7%)Positive7 (6.6%)13 (38.2%)20 (14.3%)Total106 (100%)34 (100%)140 (100%) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-05-08.

The current state of breast cancer classification

Breast cancer is a highly heterogeneous disease due to its diverse morphological features, the variable clinical outcome and the response to different therapeutic options. It is therefore necessary to devise a clinically meaningful classification of the disease, which has to be scientifically sound, clinically useful and widely reproducible. The established histopathological classification has a limited clinical utility, due to insufficient prognostic and predictive power. More recent classification schemes, based on the immunohistochemical characterization of breast cancer for the assessment of hormone receptor status, HER2 gene over-expression or amplification and the proliferative fraction or on gene expression profiles, correlate much better with the clinical outcome and may be used to inform the choice of the systemic therapy.

Epigenetics of estrogen receptor-negative primary breast cancer

Increasingly, breast cancer is being recognized as a heterogeneous disease comprised of molecularly and phenotypically distinct intrinsic tumor subtypes with different clinical outcomes. This biological heterogeneity has significant implications, particularly as it relates to expression profiling of estrogen receptor (ER) status, as classifying breast cancers based on hormone receptor expression impacts not only prognosis but also treatment options and long-term outcomes. Epigenetics has emerged as a promising field for the assessment of hormone receptor status. Epigenetic aberrations have been shown to regulate ER and offer reversible targets for development of new therapies. This review covers ER-negative breast tumor epigenetic aberrations and summarizes the major epigenetic mechanisms governing ER expression and how it impacts treatment of ER-negative breast cancer.

P2-18-01: The Magnitude of Trastuzumab Benefit in HER2−Positive (HER2+) Lobular Breast Carcinoma (BC): Results of a HERA Trial Sub-Group Analysis.

Abstract Background: Invasive lobular carcinoma (ILC) represents the second most common BC subtype and is often characterized as hormone receptor positive and HER2−negative. However a small subset of ILC is found to be HER2+. Isolated case reports have demonstrated high responsiveness to trastuzumab in patients with advanced HER2+ ILC. The HERA trial compares 1 or 2 years of trastuzumab treatment with observation and 1 versus 2 years of trastuzumab treatment after standard chemotherapy in women with HER2+ breast cancer. We sought to evaluate the incidence of HER2+ ILC and the magnitude of trastuzumab benefit in HER2+ ILC in the context of the HERA trial. In addition, we sought to describe the pattern of hormone receptor positivity in the subsets of ILC and invasive ductal carcinoma (IDC) Methods: The database used in the analysis had a clinical cut-off date of 9th June 2008 and 4-year median follow-up (Gianni et al., 2011). Patients randomized to the 1-year trastuzumab and observation arms were included in the present analysis. Central assessment of hormone receptor status was considered. Histological BC subtype was assessed locally. Results: Of the 1703 women randomized to one-year of trastuzumab and 1698 to observation, 5.5% (n=187) and 94.5% (n=3213) were diagnosed as HER2+ ILC and IDC, respectively. Central hormone receptor status was available in 88.3% (n = 2838) of IDC and 86.1% (n=161) of ILC. ER and/or PR positivity was more common in ILC than IDC (63.4% [102/161] vs. 46.3% [1314/2838]; p&amp;lt;0.001). Allred scores for ER are shown in the table below. The DFS hazard ratios comparing one year of trastuzumab versus observation were 0.63 (95% CI 0.34−1.14) for ILC and 0.77 (95% CI 0.67−0.89) for IDC. There was no evidence of an interaction between histological subtype and trastuzumab benefit (interaction [subtype lobular and subtype ductal and not lobular] p=0.49). Conclusion: HER2+ ILC accounts for 5.5% of patients included in a large population of over 3,000 HER2+ BC. While only a limited number of patients with ILC was enrolled, this analysis suggests an increased ER positivity in ILC compared to IDC. There was no suggestion that patients with HER2+ ILC derived a different magnitude of benefit from adjuvant trastuzumab when compared to the HER2+ IDC cohort. The lack of central pathology review for BC subtype assessment is a caveat of our study. Future research in the field of ILC and particularly in the HER2+ subset should be encouraged. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-01.

Immunochemistry for oestrogen receptor, progesterone receptor and HER2 on cell blocks in primary breast carcinoma

Steroid receptors and human epidermal growth receptor 2 (HER2) have been used for predicting response to treatment in breast cancers. Fine needle aspiration cytology can provide highly cellular material and can be used for such analysis. The present study was undertaken to assess the reliability of oestrogen and progesterone receptor (ER, PR) status and HER2 as demonstrated by immunochemistry (IHC) on cell blocks from breast carcinoma cases, in comparison with histological sections. IHC for ER, PR and HER2 was performed on cell blocks and their corresponding tissue sections of 50 primary pre-chemotherapy breast carcinomas. Positivity for ER and PR was scored according to the Allred scoring system. Strong membranous positivity in more than 30% of tumour cells was considered positive for HER2. The tumours were classified as luminal A, luminal B, HER2-over-expressing and triple negative on the basis of ER, PR and HER2 status and results on cell blocks compared with histological sections. Correlation between immunostaining on cell blocks and the corresponding tumour tissues revealed a concordance rate for ER, PR and HER2 of 90% [Correlation coefficient (r) = 0.79], 94% (r = 0.86) and 90% (r = 0.76), respectively. Including five cases in which cell blocks were either ER or PR positive, 43/50 cases (86.0%) could be correctly classified on cell block immunostaining alone. The main reasons for seven discordant cases included technical errors (sampling error and staining error) and interpretational error in HER2 evaluation on cell blocks; the core biopsy was inadequate in one, and apparently false negative for HER2 in another. Cell blocks are useful in the assessment of hormone receptor status and HER2 by IHC, especially in cases of locally advanced breast cancer for planning neoadjuvant chemotherapy. It is highly recommended to have good quality cell blocks and quality control of their interpretation.

Quality assurance in immunohistochemistry – an update

Introduction Diagnosis of tumours and treatment decisions for patients including breast cancer patients are based on determination of immunohistochemistry biomarkers. The accurate assessment of hormone receptor status in breast cancer and the correct classification of lymphomas is essential for appropriate patient care. The immunohistochemistry (IHC) Quality Assurance Program (QAP) includes a number of modules: diagnostic, lymphoma markers, breast markers, bright-field HER2 ISH and technical. Other countries have similar quality assurance programs. 1,2 Methods The IHC modules consist of a number of technical exercises per year with assessment of different biomarkers. The technical module evaluates different biomarkers across a range of antibodies that would be important for diagnosis of tumours. The diagnostic module allows participants to select a panel of antibodies to obtain a correct diagnosis mimicking real patient samples. The breast markers module evaluates oestrogen receptor, progesterone receptor and HER2 with a separate component for bright-field HER2 ISH testing. An audit of patient results is also performed for the breast biomarkers. The lymphoma module is used to assess markers used for classification and diagnosis of both Hodgkin’s disease and non-Hodgkin’s lymphoma. Slides are sent to participants comprising either tissue microarray blocks or composite blocks from different tissues. Homogeneity and stability testing are performed on the sections and every 20th section is stained to ensure representative tissue. Antigenic site stability is also evaluated. Slides are stained by the participating laboratory and returned for evaluation by a committee of scientists and a pathologist. Each slide is evaluated independently and an average score is returned. Each slide is scored from 0 to 5. The assessment criteria used are: • intensity of true positivity is of reasonable strength • absence of background staining (good signal to noise ratio) • sensitivity – all target tissues labelled • localisation – only target antigenic sites labelled • chromogen character – crisp and distinct • counterstain quality – complementary not obscuring • absence of artifacts • adequacy of controls – sufficiently sensitive. A score A control slide is also assessed as satisfactory, borderline or unsatisfactory. Results Participants’ results vary depending on the module being assessed and there has generally been an improvement of results over time, however deficiencies are still noticed for some biomarkers. Results of some of the modules will be presented. Discussion Immunohistochemistry is used to diagnose patients’ tumours and to determine patient treatment. Poor quality IHC will therefore have a significant impact on patient outcome. It is therefore essential that the results generated by the laboratory are accurate. External QAP forms an essential part of laboratory assessment. Participants frequently comment that the supplied material from the QAP is different to their in-house samples and that because the in-house controls worked the results are correct. This statement does not recognise the difference between Quality Control and Quality Assurance. The in-house controls, even if placed on the same slide, are Quality Controls and indicate that the antibody and the detection system are working. They do not indicate whether the result obtained is in fact correct and accurate. This is well recognised in clinical pathology where a method is validated against a reference method to determine accuracy and then QC is run internally to ensure that the reagents and instruments are working. In many cases for immunohistochemistry the controls selected are inappropriate, excessively large, show fixation variation or only reflect one level of staining. Conclusion High quality IHC results are essential to enable treating clinicians to optimise therapy for patients. The introduction and expansion of a specific quality assurance module for immunohistochemistry has enabled an ongoing assessment of the performance of biomarkers in Australia, New Zealand and South-East Asia. Despite the extraction of large amounts of information in regards to the methodology used for staining, it is usually not possible to identify one specific method that results in optimal staining although sample methods with high marks are reported. Optimisation of retrieval for a wide range of sensitivities is considered to be the important factor in achieving satisfactory results. The development of the program has resulted in an improvement in the staining quality for a number of biomarkers. Comments in this report were prepared for and on behalf of the RCPA QAP.

Abstract ED01-02: Targeting ER and HER-2 in breast cancer

Abstract ED01-02: Targeting ER and HER-2 in breast cancer

Immunohistochemical assessment of hormone receptor status of breast carcinoma : Interobserver variation of the quick score

Immunohistochemical (IHC) assessment of estrogen receptor (ER) and progesterone receptor (PR) status has become a routine practice to predict the likely outcome of Tamoxifen therapy. To assess the interobserver variation in scoring hormone receptor status of breast carcinoma, using the Quick Score. IHC-stained slides of breast carcinomas reported by the two authors during a 28-month period were included in the study. Both authors independently reassessed all the tumors. Both were blinded to each other's assessment. The Quick score with a 0-8 point scale was used to score the hormone receptor status. Weighted Kappa was calculated to assess the interobserver variation. A total of 210 breast carcinomas were included in this study. There was a substantial to almost perfect agreement between the two observers in scoring the hormone receptor status (kappa values; ER=0.856, PR=0.711). Both ER and PR showed an almost perfect agreement in assessing the intensity of staining (kappa value; ER=0.882, PR=0.840), while the scoring of proportion of cells gave lower Kappa values (kappa value; ER=0.778, PR=0.592). Interobserver agreement was less in scoring hormone receptor status of breast carcinomas after mastectomies compared with excision biopsies, wide local excisions and metastatic deposits in lymph nodes. Suboptimal fixation resulting in background staining has contributed to the variation. A substantial to almost perfect interobserver agreement was seen in assigning an overall Quick score. Detection of complete negative and strong expression had a moderate to substantial agreement.

Assessment of hormone receptor status in breast cancer

The aim of the present paper was to investigate the most adequate method for the assessment of hormone receptor status in breast cancer in routine clinical settings. Subjects were 486 patients with primary breast cancer who underwent surgery and postoperative tamoxifen monotherapy in 1982-1993. Using representative sections of the primary lesion in each patient, estrogen receptors (ER) were immunohistochemically stained. Patients were divided into ER-positive and ER-negative groups using various methods, and then overall and 5 year recurrence-free survival rates were compared. The results of ER status, which are diagnosed on entire cancer area and invasive cancer area, matched in 98% of cases. When assessing prognosis based on the proportion of positive cells, a significant difference in 5 year recurrence-free survival was seen between ER-positive and ER-negative patients for a cut-off of 10%, and in overall and 5 year survival for a cut-off of 33%. Based on the proportion and the intensity of positive cells (Allred score), a significant difference was seen in overall and 5 year survival for a cut-off in total scores between 4 and 5 points. When assessing hormone receptors of breast cancer in routine clinical settings, it is sufficient to determine the proportion of positive cells in the entire cancer area.

Immunohistochemical assessment of hormone receptor status using a new scoring system (J-score) in breast cancer

The assessment of hormone receptor status in breast cancer is essential to decide whether endocrine therapy is indicated or not. Immunohistochemistry (IHC) is thought to be the best method for examination of estrogen receptor (ER) and progesterone receptor (PgR) in routine practice. However, the cutoff point of IHC is still controversial. The St. Gallen consensus meeting in 2005 demonstrated that in patients with more than 10% ER stained tumor cells, hormone therapy will be " effective " but in those with 1 to 10% ER stained tumor cells will have an " uncertain " response. Based on the cutoff value of the St. Gallen consensus meeting, a new scoring system (J-Score) which only evaluates the positivity cell rate without taking the staining intensity into account was established. In this paper, the ER status results of 486 patients evaluated by the J-Score and A-Score (Allred Scoring system) were compared. The " uncertain " patients with ER positive cells 1 to 10% (J-Score 2) composed only 0.9% and " borderline " cases (A-Score 3 to 4) including " uncertain " cases (J-Score 2) composed 3.2% of the total patients. Thus, the number of patients determined as " uncertain " by the J-Score is very small and the number considered " borderline " by the A-Score is slightly larger. Although the J-Score system is thought to be easy and convenient for evaluating ER status in routine practice and the cutoff values adjusted to St. Gallen recommendation might be meaningful for clinical studies, many pathological and clinical studies are necessary before it is accepted as a standard method.

Recent trends of hormone receptor research and new strategy of endocrine therapy for breast cancer

Recently endocrine therapy of breast cancer has been changed because of the introduction of aromatase inhibitors for postmenopausal patients. In addition, examination methods of hormone receptor status have become unified in the immunohistochemical method and optimal evaluation criteria have been found necessary. On the other hand, fundamental research as to function of stromal cells of breast tissue has focused on the relation to postmenopausal estrogen secretion. In this special issue, we focus on recent trends of fundamental research about estrogen production in the breast tissue, methods of immunohistochemical evaluation of hormone receptor status and recent strategy of endocrine therapies for breast cancer patients. In the first review, Dr. Yamaguchi explained about the microenvironmental regulation of estrogen function in breast cancer tissue and demonstrated the relationship of activity of ER and mechanism of cancer proliferation. In addition, the mechanism of aromatase production by stromal fibroblast and growth of breast cancers was precisely explained. In the second review, Dr. Oyama described the effects of fixation and processing for adequate immunohistochemical detection of hormone receptors in breast cancer and recommended performing suitable handling of tissues and staining for accurate evaluation of hormone receptor status in routine practice. In the third review, I described two scoring systems for immunohistochemical assessment of hormone receptor status. The utility of the J-Score based on the cutoff value of St. Gallen consensus meeting was presented and explained. In the fourth review, Dr.

New monoclonal antibodies to oestrogen and progesterone receptors effective for paraffin section immunohistochemistry.

Assessment of oestrogen and progesterone receptors (ER and PgR) in breast cancer is widely used for the prediction of response to endocrine therapy and as a prognostic marker. Cytosolic assays have been replaced in many centres by immunochemical techniques, which have many advantages including applicability to small samples, simplicity, and cost-effectiveness. This study describes the generation and characterisation of two novel murine monoclonal antibodies recognizing ER and PgR, designated NCL-ER-6F11 and NCL-PGR respectively, which are effective in heat-treated formalin-fixed, paraffin-embedded tissue. The antibodies have been characterized by Western blotting and by immunohistochemistry on normal and pathological breast and other tissues. NCL-ER-6F11 has been shown to compare favourably with a currently available ER antibody. These antibodies may prove of value in the assessment of hormone receptor status in human breast cancer.

Immunocytochemical assay for oestrogen receptor in fine needle aspirates of breast cancer by video image analysis

Assessment of heterogeneity in oestrogen receptor (ER) expression aims to improve prediction of prognosis and treatment assignment in breast cancer. Current assessments are performed manually and are subjective. Automated image analysis as described here objectively quantitates ER in breast cancer nuclei obtained by needle aspiration. ER was visualised by ERICA with diaminobenzidine (DAB) substrate. Various indices of ER positivity were derived from the integrated density and average density measurements of nuclear DAB. Each index was compensated for background staining by non-specific antibody binding and endogenous peroxidase activity. Total nuclear ER content (integrated optical density of stain) was strongly associated with the biopsy ER concentration determined by saturation analysis of radioligand binding (DCC), P less than 0.005. Nuclear ER concentration by image analysis (mean optical density of stain) was not associated with the DCC measurement of ER concentration, P greater than 0.05. This was attributed to technical artefacts of cytocentrifugation. Using threshold values of 5% positive cells and 10 fmol mg-1 concordance of assignment of ER status by image analysis with the DCC assay was 91%, sensitivity was 89% and specificity 100%. It was concluded that image analysis is an appropriate, easy and economic method for determining the nuclear ER status of aspirated cancer cells. Image analysis has the potential to become a powerful diagnostic tool in the assessment of hormone receptor status of breast cancer patients.