Effects of different preprocessing algorithms on the prognostic value of breast tumour microscopic images.

The purpose of this study was to improve the prognostic value of tumour histopathology image analysis methodology by image preprocessing. Key image qualities were modified including contrast, sharpness and brightness. The texture information was subsequently extracted from images of haematoxylin/eosin-stained tumour tissue sections by GLCM, monofractal and multifractal algorithms without any analytical limitation to predefined structures. Images were derived from patient groups with invasive breast carcinoma (BC, 93 patients) and inflammatory breast carcinoma (IBC, 51 patients). The prognostic performance was indeed significantly enhanced by preprocessing with the average AUCs of individual texture features improving from 0.68 ± 0.05 for original to 0.78 ± 0.01 for preprocessed images in the BC group and 0.75 ± 0.01 to 0.80 ± 0.02 in the IBC group. Image preprocessing also improved the prognostic independence of texture features as indicated by multivariate analysis. Surprisingly, the tonal histogram compression by the nonnormalisation preprocessing has prognostically outperformed the tested contrast normalisation algorithms. Generally, features without prognostic value showed higher susceptibility to prognostic enhancement by preprocessing whereas IDM texture feature was exceptionally susceptible. The obtained results are suggestive of the existence of distinct texture prognostic clues in the two examined types of breast cancer. The obtained enhancement of prognostic performance is essential for the anticipated clinical use of this method as a simple and cost-effective prognosticator of cancer outcome.

Change of influence of prognostic markers on metastasis free interval during and after adjuvant tamoxifen therapy in breast cancer patients.

PURPOSE: To evaluate the influence of molecular biomarkers (estrogen receptor - ER, progesterone receptor - PR, and human epidermal growth factor receptor2 - HER2) and pathological parameters on metastasis free interval (MFI) in adjuvantly tamoxifen-treated breast cancer patients, during different follow up periods (0-2.5 years, 2.5-5 years and 5-12 years). METHODS: The study included 113 postmenopausal breast cancer patients with known pathological parameters. Steroid receptors were determined by ligand-binding assay and HER2 amplification status by chromogenic in situ hybridization (CISH). RESULTS: During the first 2.5 years of therapy patients with ER <5 fmol/mg, PR <5 fmol/mg or pT2 (≥2cm) tumors had higher probability of distant metastasis. For the period between 2.5-5 years, analysis of MFI according to pathological parameters and molecular biomarkers, separately, did not show any statistically significant difference. Patients with pT≥2 cm and HER2 amplification had much greater chance of developing distant metastasis when compared to other phenotypes (HER2-negative/pT1, HER2-negative/pT2 and HER2-positive/pT1). Patiens with ER ≥160 fmol/mg and PR ≥45 fmol/mg had good prognosis after 5 years of tamoxifen therapy. CONCLUSION: Our study indicates that there is a change of influence of the analyzed pathological parameters on MFI, depending on different follow up periods. Steroid receptor status, tumor size and HER2 status (alone or in combination) are significant parameters for the course of disease of postmenopausal ER-positive breast cancer patients, but during different periods of follow up.

Metastatic breast cancer survival according to HER2 and Topo2a gene status.

The aim of this study was to determine the relationship between amplification of HER2 (Human epidermal growth factor receptor 2) and Topo2a (topoisomerase 2a) and their influence on prognosis in metastatic breast cancer (MBC) patients. Amplification of both HER2 and Topo2a genes was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue of 71 MBC patients. Starting point for follow-up was the time of diagnosis of metastatic disease. Although there was significant correlation between HER2 amplification and Topo2a alterations, Topo2a amplification was not strictly related to HER2 amplification. Follow-up of patients showed that there was no difference in MBC survival between HER2-nonamplified and HER2-amplified patients for subgroup as whole, but there was significant difference in MBC survival between patients with and without Topo2a amplification. HER2 amplification showed prognostic value in subgroups of patients, as well as Topo2a. Combination of these two genes with different status (nonamplified, amplified, coamplified) indicated that they might have additive effect. Also, it has been shown that Topo2a-amplified cases have poorer survival than Topo2a-nonamplified, when treated with CMF therapy. Topo2a amplification seems to be more promising biomarker of MBC survival, than HER2, and potential marker of resistance to CMF therapy.

Stage-related plasma values of transforming growth factor-beta1 are steroid receptors dependent.

Transforming growth factor-beta1 (TGF-beta1) is a biomarker associated with the progression of breast cancer, characteristic by switching activity from tumor suppressor in early stages to tumor promoter at advanced disease. However, what cause this switch is still not clear. On the other hand, the relationship between steroid receptors (estrogen ER and progesterone PR) as the major discriminators of breast cancer phenotype and this paradoxical biomarker is not fully determined. In this pilot study on 52 breast cancer patients, quantitative plasma values of TGF-beta1 were determined by quantitative ELISA and steroid receptor content was measured in cytosol fraction of breast cancer tissue using dextran-coated (DCC) method. We tried to investigate the possibility that steroid receptor status of patients at different stages of disease could be the trigger that somehow causes variation of TGF-beta1 plasma levels. In nonmetastatic breast cancer patients, there was no statistically significant increase in the plasma levels of TGF-beta1, when patients are stratified by steroid receptor status (ER- vs. ER+, PR- vs. PR+). We found for the first time, that indeed in metastatic breast cancer statistically significant elevated levels of TGF-beta1 are related to negative steroid receptor status and moreover that, there is correlation between quantitative values of these parameters in this stage. This finding deserves further investigation because it could provide a new insight into more aggressive nature of steroid receptor negative tumors.

Cathepsin D-related disease-free interval in pT1 primary breast carcinomas: a pilot study.

In order to address the heterogeneity of the pT1 breast cancer stages, we have been examining the natural and the clinical course of disease in relation to cathepsin D expression, as a molecular marker for the tumor progression that leads to metastasis. The original aim of our pilot study was to determine whether it was possible to distinguish high-risk from low-risk patients, on the basis of nonestrogen- vs. estrogen-regulated cathepsin D expression. Our results showed that estrogen-regulated cathepsin D expression could be useful as surrogate marker of node-positive status. Further, during the natural course of disease, none of 7 pT1N0 patients with tumors bearing nonestrogen-regulated cathepsin D expression developed metastasis. During the clinical course of disease, nonestrogen-regulated cathepsin D expression defined low-risk while estrogen-regulated cathepsin D expression defined high-risk pT1N+ subgroup of patients. Although there is no consensus with respect to metastasis-related prognostic value of cathepsin D expression, our pilot study implies its prognostic value in pT1 breast cancer patients and supports the hypothesis that cathepsin D may promote metastasis in this early stage of disease.

The influence of steroid receptors status on disease outcome in early breast cancer patients treated with adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy.

PURPOSE: To assess the influence of steroid receptors (SR) status on disease outcome of early breast cancer patients treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy. PATIENTS AND METHODS: Sixty-six node-negative patients with grade 3 invasive breast carcinoma and 95 patients with 1-3 involved axillary lymph nodes regardless of tumor grade received adjuvant CMF chemotherapy. The endpoints of this analysis were disease-free survival (DFS) and overall survival (OS). Statistical analysis included log rank test and Cox regression models. RESULTS: The median follow-up period was 81 months (range 6-208). Patients with progesterone receptor (PR) - negative tumors had better DFS compared to women with PR-positive tumors (log rank test, p=0.033). Estrogen receptor (ER) - negative and PR-negative patients in the node-negative subgroup had better DFS than ER-positive and PR-positive patients (for ER: log rank test, p=0.009, and for PR: log rank test, p=0.004). However, positive lymph nodes were the only significant predictor of disease progression among patients receiving CMF therapy (Likelihood Ratio test, p <0.001). Women under 40 bearing SR-positive breast cancer had a trend toward worse DFS (log rank test, p=0.054) compared to older SR-positive premenopausal women. CONCLUSION: We can not unequivocally reveal the influence of SR status on disease outcome in early breast cancer patients treated with adjuvant CMF, although SR-positive patients in the node-negative group were shown to have worse DFS in comparison to SR-negative ones. However, nodal status remained the only independent predictor of disease progression in these patients.

Primarily tamoxifen-unresponsive, steroid receptor-positive breast cancer may respond to an aromatase inhibition: a pilot study.

PURPOSE: Breast carcinomas becoming tamoxifen-resistant after objective clinical response to antiestrogen therapy may remain responsive to other endocrine agents due to different mechanisms of action. The aim of our study was to analyze whether primarily tamoxifen-unresponsive/steroid receptor (SR) - positive breast carcinomas can respond to an aromatase inhibition. PATIENTS AND METHODS: Thirteen postmenopausal, SR-positive, metastatic breast cancer (MBC) patients were included: they had previously failed to respond to tamoxifen, either as primary systemic therapy for advanced disease, or as adjuvant treatment (5 and 8 patients, respectively). Patients were treated with 2.5 mg letrozole daily, from 2-25 months, mostly until disease progression. RESULTS: Partial response (PR) was obtained in one third of the patients (4/13); additionally, 3 patients showed disease stabilization (SD) longer than 6 months. The observed response duration lasted from 7 to 36+ months (median 9). Overall survival from the beginning of letrozole treatment was better in letrozole responders compared with nonresponders. It appeared as if there were two different subgroups of patients: one completely endocrine-unresponsive, and the other unresponsive to tamoxifen but responsive to letrozole (supposed to be primarily tamoxifen-resistant, but otherwise endocrine-responsive). HER-2 overexpression (immunohistochemically determined as 2+ and 3+) was found in 3 patients, which could not account for the different endocrine responsiveness. CONCLUSION: Our study confirmed that some SR-positive breast carcinomas, primarily tamoxifen-unresponsive, may respond to letrozole, thus being endocrine-responsive, while others did not respond, probably due to complete endocrine unresponsiveness. It is not likely that HER-2 was the biomarker that made the difference between these two subgroups.

Localization of recognition site between transforming growth factor-beta1 (TGF-beta1) and TGF beta receptor type II: possible implications in breast cancer.

Although overexpression of TGF-beta1 protein has been demonstrated in advanced breast cancer (BC) patients, as well as in other solid tumours, the molecular mechanism of this process remains obscure. This paper proposes that a genetic/epigenetic alteration might occur in the TGF-beta1 gene, within the region coding for the recognition site with TGFbeta receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta1 cascade-related BC progression. To establish the operational framework for this hypothesis, in the present study, this recognition site was identified by the Informational Spectrum Method (ISM) to comprise two TGF-beta1 peptides (positions 47-66 aa and 83-112 aa) and one receptor peptide at positions 112-151 aa of the extracellular domain of the receptor (TbetaRIIM). The TbetaRIIM locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta1 analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta1 MAb (MAb) and other with TbetaRIIM as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta1 elevation. In MAb-profile, the TGF-beta1 increase was detected in 7 of 8 patients, whereas analogous TbetaRIIM-profile revealed the elevation in 3 of 8 patients, taking a 50% of maximal elevation as the cut-off value. These findings are consistent with the proposed aberration of TGF-beta1 ligand within the TbetaRII recognition site. Summarizing, this model system is a good starting point for further genetic studies, particularly on genetic/epigenetic alterations of sequences involved in TGF-beta1 and TbetaRIIM interaction, with putative prognostic value for breast cancer.

Plasma TGF-beta1-related survival of postmenopausal metastatic breast cancer patients.

A pilot study was conducted to assess whether plasma levels of transforming growth factor-beta1 (TGF-beta1) might facilitate biological subgrouping of postmenopausal metastatic breast cancer patients, and, accordingly, its applicability in clinical oncology. This study included 29 postmenopausal metastatic breast cancer patients. Plasma TGF-beta1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Estrogen and progesterone receptors were assayed by radioligand binding, in accordance with the recommendation of the EORTC. Concentrations of 17-beta estradiol were determined by using ELISA-microwell method (DIALAB). Overall survival was followed for 24 months for each individual patient. Stratification of the patients by ER/PR status showed that 14 patients with estrogen receptor-negative, progesterone receptor-negative carcinomas displayed a statistically significant increase in plasma TGF-beta1 levels when compared to plasma TGF-beta1 levels of 6 patients with ER-positive, PR-positive carcinomas (P=0.04). In this study, 7 out of 14 patients with negative receptors' status had no plasma TGF-beta1 values overlapping with patients having positive receptors' status. The TGF-beta1 cut-off value was defined as the highest plasma TGF-beta1 level of ER-positive, PR-positive patients: 3.28 ng/ml. This plasma TGF-beta1 cut-off value defined low-risk subgroup of 19 patients (< or = 3.28 ng/ml) and high-risk subgroup of 10 patients (> 3.28 ng/ml) (P=0.047). Plasma TGF-beta1-related survival was independent of the classical prognostic factors of metastatic breast cancer. Accordingly, a clinical significance of elevated plasma TGF-beta1 levels may be suggested.

Natural course of node-negative breast cancer: high risk-related subgroups.

This study attempted to evaluate the first-generation prognostic factors in terms of relapse-free interval in 297 node-negative breast cancer patients treated with locoregional therapy alone. Predictors of outcome were, in order of strength: tumor size (RR 2.09), tumor grade (RR 2.03) and age (RR 0.97). Age was a single independent prognostic parameter in premenopausal patients younger than 45 (RR 0.82). Tumor size was also a single independent prognostic parameter in middle-aged patients (RR 2.05). In older patients, aged 60 and over, tumor grade (RR 11.6) and type (RR 0,52) in addition to tumor size (RR 7.00) were independent prognostic parameters. Our study of disease-free survival identified high risk-related subgroups: patients younger than 35, middle-aged post-menopausal patients bearing pT2 carcinoma with steroid receptor content lower than 5 fmol/mg, and patients older than 59 bearing pT2 carcinoma with grade 11 and unfavorable types-ductal, lobular.

Natural history of estrogen receptor-negative, progesterone receptor-positive breast cancer.

The biological significance of estrogen receptor-negative but progesterone receptor-positive breast carcinomas is not clear. In the present study the aggressiveness of breast carcinomas in relation to ER and PgR status has been investigated. The probability of disease-free survival in 297 node-negative breast carcinoma patients was monitored during a follow-up ranging from six to 96 months (median 45 months). Steroid hormone receptor content was assayed with the biochemical method recommended by the EORTC. The probability of disease-free survival was significantly worse for patients with ER-negative, PgR-positive carcinomas compared to the other three steroid hormone receptor phenotypes. Our results suggest that ER-negative, PgR-positive breast carcinomas are biologically different in terms of aggressiveness from the other steroid hormone receptor phenotypes.

Progesterone receptor status of breast cancer metastases.

PURPOSE: The usefulness of steroid receptor content in breast cancer metastases for metastatic disease therapy planning was examined in this study. METHODS: Steroid receptors in primary tumors and corresponding metastases in the same breast cancer patients ( n=23) were determined by five-point DCC assay. We carried out an analysis of the therapeutic response and comparison of the progression-free interval of patients treated with endocrine/chemo-endocrine therapy for metastatic disease according to the positive/negative progesterone receptor status of primary tumors, or of breast cancer metastases. RESULTS AND CONCLUSIONS: It seems that the lack of positive progesterone receptors in metastasis (0/8) and conversion from PR+ primary to PR- metastasis (5/8) may be important in describing the non-responder phenotype. We obtained a similar progression-free interval in patients with progesterone receptor-positive/negative primary tumors, but a longer progression-free interval in the patients with progesterone receptor-positive metastases ( n=9) than with negative ones ( n=14), indicating the possibility of using steroid receptor content from metastases for metastatic disease therapy planning.

PS2 protein in breast carcinomas: cut-off value of estrogen-regulated expression.

This study includes 152 patients with histologically confirmed breast carcinoma. Steroid hormone receptors (SR), estrogen (ER) and progesteron (PR) receptors, and pS2 protein were assayed on the same cytosolic extract in accordance with the recommendation of EORTC. Our results showed menopausal- and histologic grade-related expression of pS2 protein. Unfavorable carcinoma subgroups, in relation to expression of pS2 protein were defined: postmenopausal carcinomas with histologic grade II, and pre-, as well as postmenopausal carcinomas with histologic grade III. There were overlappings of individual pS2 protein values between favorable and unfavorable carcinoma subgroups in relation to the expression of pS2 protein. Otherwise, no overlapping of pS2 protein values was obtained between ER-positive and ER-negative carcinomas within defined unfavorable menopausal - and histologic grade-related expression of pS2 protein subgroups. The highest pS2 protein level observed in ER-negative unfavorable subgroups (15 ng/mg) was considered as the cut-off value which defined estrogen-regulated expression of pS2 protein.

Content of epidermal growth factor receptor in metastatic breast cancer: its role in endocrine sensitivity prediction.

Epidermal growth factor receptor (EGF-R) is known as an indicator of endocrine independence of breast cancer. However, a small proportion of EGF-R expressing tumors was found to respond to endocrine treatments. On the other side, a cut-off point of EGF-R positivity is not yet defined. In the aim to find out whether there exists a cut-off value that sharply discriminate the endocrine sensitive and endocrine insensitive breast cancers, the quantitative EGF-R content was analyzed in a group of 42 female patients with metastatic disease, being routinely treated with chemo-, chemo-endocrine, or endocrine therapy alone. Steroid receptors (SR) and EGF-R were determined by biochemical methods in tissue samples of an unselected group of patients. Patients with metastatic disease, either at diagnosis, or developed after the treatment of operable or locally advanced breast cancer, were included in the present analysis. According to the treatments used, and their therapeutic response, all patients were divided in endocrine sensitive or resistant, and chemo-sensitive or resistant. The SR and EGF-R status and content was analyzed in relation to the sensitivity to both systemic treatments. The EGF-R content was significantly lower in responders to endocrine treatments, compared to non-responders, while there was no difference in EGF-R level, in relation to the sensitivity to chemotherapy. In addition, the EGF-R content was significantly higher in chemo-sensitive tumors, than in endocrine sensitive. On the contrary, ER content was significantly higher in endocrine sensitive, than in endocrine resistant, and in chemo sensitive patients, as well. Similar differences were found in PR content, but they were less pronounced. While the individual ER contents in endocrine sensitive and endocrine resistant tumors overlapped, the EGF-R ranges were different: no one endocrine sensitive tumor exceeded the EGF-R content of 26 fmol/mg, thus suggesting the EGF-R cut-off point of endocrine sensitivity. The clinical use of EGF-R, with the cut-off point of 26 fmol/mg, in addition to clinical criteria of endocrine sensitivity and SRs, would significantly improve the correct endocrine sensitivity prediction (from 52 to 78%). In conclusion, in a group of metastatic breast cancer patients, treated routinely by systemic therapies it was found, that the use of higher cut-off point for EGF-R positivity can improve the prediction of endocrine sensitivity. The prognostic relevance of this cut-off value remains to be analyzed.

Expression of epidermal growth factor receptor in breast cancer, from early stages to advanced disease.

Epidermal growth factor receptor was determined in 106 newly diagnosed breast cancer patients, using the biochemical method. The group consisted of 58 patients in stage I-II, and 48 patients in stage III-IV. Although a significant inverse correlation was found between EGF-R status, and ER or PR status, quantitative content of EGF-R did not correlate either with quantitative ER, or PR levels. The ER/PR content was similar in all clinical stages, suggesting their stability during the clinical course of the disease. EGF-R content was significantly higher in stage IV, compared to stage I, while intermediate clinical stages and all substages did not differ according to the EGF-R content. EGF-R was confirmed as a weak prognostic factor within clinical stages. However, in a whole group, the overall survival was significantly better in patients whose tumors EGF-R content was lower than 26 fmol/mg, compared to those with higher ERF-R content. EGF-R content was highly predictive for the response to systemic endocrine treatment, in metastatic breast cancer patients. In locally advanced breast cancer a trend towards higher levels of EGF-R was found in inflammatory breast cancers, compared to non-inflammatory ones. Slightly higher levels were found in responders to local non-endocrine primary treatments (radiotherapy with or without chemotherapy), compared to non-responders, suggesting the possible predictive role of EGF-R for the response to such treatments. Our results emphasized the usefulness of quantitative receptor determination suggesting the relative stability of EGF-R content during the clinical course of breast cancer, its independence from ER, its significant predictive and weak prognostic values, and a possible correlation with the aggressiveness of the disease, and response to non-endocrine treatments.

Cathepsin D: association between TN-stage and steroid receptor status of breast carcinoma.

PURPOSE: To assess whether the expression of estrogen-induced protease, cathepsin D, might facilitate biological subgrouping of patients with breast carcinomas, and accordingly, its potential applicability in clinical oncology. PATIENTS AND METHODS: This study includes 70 patients with histologically confirmed breast carcinoma. Pathological findings were classified according to tumor size (T) and the presence or absence of metastases in regional lymph nodes (N). Steroid hormone receptor (SR) density as well as cathepsin D concentrations were assayed in the cytosol of breast carcinomas in accordance with the recommendation of the EORTC. RESULTS AND DISCUSSION: Statistically significant direct correlations were observed between cathepsin D expression and axillary node status as well as SR status. However, it is important to point out that in spite of these statistically significant findings, there were no biologically significant associations due to a wide range of individual cathepsin D values. Baseline levels of cathepsin D expression were found in patients with SR-negative status and node-negative tumors as well as in patients with SR-negative status and tumors of

pS2 in breast carcinoma: association with steroid hormone receptor status.

AIMS AND BACKGROUND: Knowledge of the steroid hormone receptors has proved to be of significant value in breast cancer. In the present study the possible importance of estrogen-regulated pS2 protein was investigated. Our direct purpose was to answer the question whether the expression of pS2 may be a marker of functional heterogeneity with respect to the steroid hormone receptor status. METHODS AND STUDY DESIGN: The study included 152 patients with primary, operable, histologically confirmed breast carcinomas. Histology specimens were reviewed and classified according to type, nodal status, tumor size and grade. Steroid hormone receptors were assayed by biochemical methods according to the procedures recommended by the EORTC. pS2 protein measurement was performed in breast carcinoma cytosols using an immunoradiometric assay. The results were analyzed by non-parametric statistical methods. RESULTS: A statistically significant inverse correlation between pS2 protein expression and histological tumor grade was found. The expression of pS2 protein was confirmed to be correlated with steroid hormone receptor status. However, it is important to point out that in spite of these statistically significant findings there were no significant biological associations due to overlapping individual pS2 protein values. The baseline level of expression of pS2 protein was obtained in histological grade III carcinomas with a negative steroid hormone receptor status. It was shown that the distribution of carcinomas according to the baseline level of pS2 protein expression was heterogeneous among estrogen receptor-positive carcinomas, and strikingly homogeneous among estrogen and progesterone-negative carcinoma. CONCLUSION: Our study suggested that PR and pS2 protein may identify distinct subsets of estrogen receptor-positive breast carcinomas.

Evaluation of the nutritional status and tumor characteristics in premenopausal and postmenopausal breast cancer patients.

Evaluation of the nutritional status, fat tissue distribution, and tumor characteristics was carried out in patients with primary breast cancer. The patients were classified into two groups according to their menopause: premenopausal and postmenopausal. Breast cancer prevalence was considerably higher in postmenopausal patients (61%). The patients' nutritional status was shown through the body mass index. Based on this indicator, the patients were characterized as nonobese and obese. In the premenopausal group, there was no significant difference between these categories, whereas the number of obese patients was significantly higher (80%) in the postmenopausal group. The analysis of tumor parameters as related to menopause and body size did not yield any significant differences. However, the estrogen receptor content was significantly higher in postmenopausal patients (p < 0.0001). Distribution of fat tissue of the android type was higher in obese postmenopausal women than in premenopausal ones (77%). The investigation showed that the breast cancer incidence odds are 3.5 times higher in obese postmenopausal than in premenopausal patients.

Variations in steroid hormone receptor content throughout age and menopausal periods, and menstrual cycle in breast cancer patients.

Variations in steroid hormone receptor contents throughout age and menopausal periods define three breast carcinoma groups: younger premenopausal carcinomas (aged up to 45), middle-aged carcinomas (pre-, peri- and postmenopausal aged 45-59) and older postmenopausal carcinomas (aged over 59). Age-related steroid hormone receptor contents within premenopausal and postmenopausal carcinoma groups are characterized by the important increase of both receptor contents, while menopausal-related steroid hormone receptor contents within middle-aged carcinoma group (aged 45-59) are characterized by the important decrease of progesterone receptor content and estrogen receptor functionality. No variations in steroid hormone receptor contents throughout menstrual cycle within the follicular and the luteal phases were obtained. The important decrease of estrogen receptor content in the mid-cycle phase versus the perimenstrual phase was found. Variations in steroid hormone receptor contents throughout age and menopausal periods, as well as throughout menstrual cycle could not be associated with variations in the blood steroid hormone concentrations. However, important association between steroid hormone receptor contents and the blood steroid hormone concentrations was found within the luteal phase carcinoma group and within older postmenopausal carcinoma group. It is interesting that within carcinoma group with the highest concentration of progesterone, progesterone receptor content increases with an increase of the ratio of estradiol and progesterone blood concentrations, while within carcinoma group with the lowest steroid hormone concentration and the highest content of estrogen receptor content, estrogen receptor content decreases with an increase of either the blood estradiol concentration or the ratio of the blood estradiol and progesterone blood concentrations.

Steroid receptors in pleural effusions of advanced breast cancer patients.

The steroid receptor content in breast carcinoma correlates with the responsiveness of malignant cells to endocrine manipulation. Although the steroid receptor status of the primary tumor is mostly used to select systemic therapy, it was suggested that steroid receptor content should be evaluated in metastatic lesions whenever possible. In this study the estrogen and progesterone receptor content was determined biochemically in 38 pleural effusions from advanced breast cancer patients. In 17/38 patients the steroid receptor status was assessed twice during the course of the disease - at diagnosis in the primary tumor/lymph nodes, and subsequently in metastatic pleural effusion fluid. A trend towards lower receptor values in pleural fluids was evident. There was no correlation between pleural steroid receptor content and pleural response to endocrine or chemo/endocrine therapy, indicating that the usefulness of effusional steroid receptors for therapy planning of advanced breast cancer could not be confirmed in this study.