***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Progesterone receptor ( PR ) antagonist aglepristone ( RU534 ) has been used successfully for pregnancy termination and therapy of pyometra , vaginal tumors , and mammary hyperplasia in bitches and queens . All of these conditions share with canine mammary carcinomas the expression of PR . OBJECTIVES To study the effect of RU534 on proliferation and apoptosis in canine mammary carcinomas in relation to PR expression . ANIMALS Twenty-seven nonspayed bitches with mammary carcinomas were treated with either 2 doses of 20 mg/kg RU534 ( n = 22 , RU534-treated group ) or oil placebo ( n = 5 , control group ) on days 1 and 8 . METHODS Tumor sample s were collected before ( day 1 ) and after ( day 15 ) treatment for immunohistochemistry . PR expression , proliferation index ( PI ) , and apoptotic index ( AI ) were determined using antibodies against PR , Ki67 , and cleaved lamin A/C antigens , respectively . The effect of treatment on these parameters was analyzed . RESULTS Differential expression of PR between day 1 ( 59.1 % PR-positive tumors ) and day 15 ( 36.4 % PR-positive tumors ) was observed in RU534-treated tumors exclusively . After RU534 treatment , mean PI was significantly decreased in PR-positive but unchanged in PR-negative RU534-treated tumors . A reduction of ≥20 % in PI was found in 61.5 % of RU534-treated tumors with PR expression . Conversely , no effect on AI was observed after RU534 treatment . CONCLUSIONS AND CLINICAL IMPORTANCE Neoadjuvant RU534 treatment had PR expression-related inhibiting effects on proliferation of canine mammary carcinoma cells BACKGROUND Nonmalignant mammary tumors ( NMT ) are common in intact female dogs . Little is known about the clinical significance of these tumors , and the effect of ovariohysterectomy ( OHE ) on their development . HYPOTHESIS Ovarian hormone ablation through OHE decreases the risk of new tumors and thereby improves long-term prognosis for dogs with NMT . ANIMALS Eighty-four sexually intact bitches with NMT . METHODS Dogs were allocated to undergo OHE ( n = 42 ) or not ( n = 42 ) at the time of NMT removal in a r and omized clinical trial . Tumor diagnosis was confirmed histologically in all subjects . Information about new tumor development was collected via follow-up phone calls and recheck examinations . Separate survival analyses were performed with the endpoints new tumor development and death . Cause of death was classified as related or unrelated to mammary tumor . In addition to OHE status , the influence of age , body weight , breed , tumor size , tumor number , tumor duration , type of surgery , and tumor histology was investigated . RESULTS New mammary tumor(s ) developed in 27 of 42 ( 64 % ) intact dogs and 15 of 42 ( 36 % ) ovariohysterectomized dogs ( hazard ratio 0.47 , P = .022 ) . Nine of the 42 dogs ( 21 % ) which developed new tumors were euthanized because of mammary tumor . Survival was not significantly different between the 2 treatment groups . In the intact group , nine dogs subsequently developed ovarian-uterine diseases . CONCLUSION Ovariohysterectomy performed at the time of mammary tumor excision reduced the risk of new tumors by about 50 % among dogs with NMT . Survival was not significantly affected . Adjuvant OHE should be considered in adult dogs with mammary tumors PURPOSE Transcription factor signal transducer and activator of transcription-5 ( Stat5 ) promotes breast epithelial cell differentiation . We retrospectively analyzed whether levels of active Stat5 in breast cancer were linked to clinical outcome . MATERIAL S AND METHODS Immunohistochemistry was used to detect active , tyrosine-phosphorylated Stat5 in paraffin-embedded breast cancer specimens from three archival tissue microarray material s A , B , and C. Material A included 19 healthy human breast tissues and a progression series of primary lymph node-negative , primary lymph node-positive , and metastatic breast cancer ( n = 400 ) . Material s B ( n = 785 ) and C ( n = 570 ) represented two independent arrays of unselected primary breast cancer specimens with clinical follow-up data . RESULTS Material A demonstrated that Stat5 activation , but not Stat5 protein expression , was gradually lost during cancer progression , with detectable activation in 100 % of healthy breast specimens compared with less than 20 % of node-positive breast cancers and metastases . Stat5 activation in tumors of material B was associated with favorable prognosis . This observation was confirmed and extended in material C to include both breast cancer-specific survival and disease-free survival . Stat5 activation remained an independent prognostic marker after adjusting for patient age , tumor size , histological grade , estrogen receptor , progesterone receptor , and Her2/neu status by Cox multivariate analysis ( hazard ratio , 2.0 ; P = .029 ) . Stat5 activation was a particularly favorable marker in the lymph node-negative breast cancer sub population ( hazard ratio , 7.5 ; P = .003 ) . CONCLUSION In our study , active Stat5 distinguishes breast cancer patients with favorable prognosis , and may be a useful marker for selection of more individualized treatment , especially in localized disease . These findings require confirmation in a large prospect i ve study The immunohistochemically determined estrogen receptor ( ER ) α ( ERα ) and progesterone receptor ( PR ) status , as well as recognized , well-accepted prognostic indicators and host factors were prospect ively analyzed in 84 cases of primary canine mammary carcinoma for their effect on disease-free period ( recurrence free , metastasis free , or combined ) ( DFP ) after an observation period of 18 months . The presence of one or both receptors , as well as tumor size , lymph node status , histologic grading , intravascular growth , and necrosis , were of prognostic value for DFP . In multivariate analysis , only tumor size and histologic grading proved to be independent prognosticators . None of the host factors analyzed were of prognostic value for DFP . ERα , PR , or both were detected in 173 out of 228 tumors : 70 ERα and PR ; 5 ERα only ; 98 PR only . Statistically significant differences regarding the presence of one or both receptors were observed between benign and malignant tumors and between complex , mixed , and simple histologic subtypes of benign and malignant tumors . In the group of malignant tumors ( n = 155 ) , the presence of one or both receptors was more frequent in tumors smaller than 3 cm , without lymph node metastasis , with tubulopapillary rather than solid patterns of growth among simple carcinomas , of histologic grade s I and II , without both intravascular growth and necrosis , and with lymphocyte cell infiltrates . The most frequent groups of hormone receptors-positive tumors were the ERα-positive and PR-positive group among benign and the ERα-negative and PR-positive group among malignant tumors The aims of this study were to investigate the serum and tissue content of and rogens and estrogens in canine inflammatory mammary carcinomas ( IMC ) as well as in non-inflammatory malignant mammary tumors ( MMT ) , and assessed the immunoexpression of estrogen and and rogen receptors using immunohistochemistry . Profiles for the and rogens dehydroepi and rosterone ( DHEA ) , and rostenedione ( A4 ) , and testosterone ( T ) , and for the estrogens 17beta estradiol ( E2 ) and estrone-sulphate ( SO4E1 ) were measured both in tissue homogenates and in serum of MMT and IMC by EIA techniques in 42 non-inflammatory malignant mammary tumors ( MMT ) and in 14 inflammatory mammary carcinomas ( IMC ) , prospect ively collected from 56 female dogs . And rogen receptor ( AR ) and estrogen receptor alpha ( ERalpha ) and beta ( ERbeta ) expression was studied using immunohistochemistry ( strepavidin-biotin-peroxidase method ) in sample s of 32 MMT and 14 IMC , and counted by a computer image analyzer . IMC serum and tissue levels of and rogens were significantly higher than MMT levels . Tissue content of estrogens was also significantly higher in IMC than in MMT . Serum values of SO4E1 were significantly higher in IMC , but serum levels of E2 were significantly lower in IMC compared to MMT cases . Medium-high and rogen receptor intensity was observed in 64.28 % of IMC and 40.62 % of MMT . No important differences were found between ERalpha expression in IMC ( 100 % negative ) and MMT ( 90 % negative ) . ERbeta and AR were intensely expressed in highly malignant inflammatory mammary carcinoma cells . To our knowledge , this is the first report relative to AR immunohistochemistry in canine mammary cancer and to estrogens or and rogens in serum of dogs with benign or malignant mammary tumors 
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Results For all receptors , the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs .
Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms , but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors .
The expression of CDH-1 was influenced by tumor malignancy and cycle stage , i.e. , the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary tissues of anestrous and spayed dogs .
Conclusions Herein , it has been confirmed that transformation towards malignant neoplasms is associated with significant reduction of gene expression of particular hormone receptors .
Only PRLR in malignant tumors seems to be influenced by circulating PRL levels .
In dogs , CDH-1 can be used as a prognostic factor ; its expression , however , in benign tumors is influenced by cycle stage