Potential clinical relevance of uPA and PAI-1 levels in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up

Buta, Marko; Džodić, Radan; Đurišić, Igor; Marković, Ivan; Vujasinović, Tijana; Markicevic, Milan; Nikolić‐Vukosavljević, Dragica

doi:10.1007/s13277-015-3573-1

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Recently, Buta et al . 24 also reported superior DFS in 73 node-negative, postmenopausal, steroid hormone receptor positive breast cancer patients with smaller tumors and low PAI-1, independent of HER2 status. On the other hand, Konecny et al .…”

Section: Discussionmentioning

confidence: 84%

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

Dovnik

Takač

2016

Radiology and Oncology

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BackgroundThe association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients.Patients and methodsA retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000–2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model.ResultsIn univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83–4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low.ConclusionsuPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting.

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Section: Discussionmentioning

confidence: 84%

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

Dovnik

Takač

2016

Radiology and Oncology

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“…MCP1 and PAI1, are found in plasma and mammary tumors from MMTV-PyMT mice (26)(27)(28). Expression of proinflammatory cytokines MCP1 (26), PAI1 (29,30), TNFα (31), and resistin (32) are elevated in invasive breast cancer. In luminal B breast cancer, increased the expression of these cytokines is associated with poor prognosis and lower overall survival (26,33,34).…”

Section: Body Weight (A) Body Fat Mass Ratio (B) Lean Mass Ratio (Cmentioning

confidence: 99%

High-fat Diet Enhances Mammary Tumorigenesis and Pulmonary Metastasis and Alters Inflammatory and Angiogenic Profiles in MMTV-PyMT Mice

Sundaram

Yan

2016

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Abstract. The Breast cancer is a heterogeneous disease with several intrinsic subtypes including luminal B breast cancer (1). Luminal B breast cancer is characterized by the expression of estrogen and progesterone receptors and overexpression of human epidermal growth factor receptor 2 and Ki67 (a marker of cell proliferation) (2). Luminal B breast cancer accounts for only 12.4% of all invasive breast cancers (3). However, it is more aggressive and of a higher grade with a worse prognosis than luminal A breast cancer (4).Epidemiological studies provide strong evidence that obesity and its associated adipose inflammation are risk factors for breast cancer, including the luminal B subtype (5, 6). Being obese at the time of diagnosis of breast cancer can be predictive of poor prognosis (7, 8); luminal B breast cancer is more frequent in obese than in non-obese premenopausal women (9). Weight gain after age 18 years is also strongly associated with the luminal B subtype (10). Furthermore, obese postmenopausal women are at a greater risk of developing luminal B breast cancer (9, 11).The MMTV-PyMT mouse model is commonly used to study luminal B breast cancer. The mouse mammary tumor virus (MMTV) long terminal repeat drives the mammary gland-specific expression of the polyoma virus middle T antigen (PyMT) and transforms the mammary epithelia, which results in mammary gland tumors (12). The mammary tumorigenesis in this model is characterized by hyperplasia, adenoma, neoplasia, and carcinoma with high incidence of lung metastasis (12, 13). Classification and hierarchical clustering analyses suggest that the MMTV-PyMT mammary tumors are similar to those of the luminal subtype (14). Further genetic and marker analyses suggest that MMTVPyMT tumors exhibit the luminal B tumor signature, including short latency and high penetrance (14,15).Studies using animal models of breast cancer support findings from human studies; obesogenic high-fat diets enhance mammary tumorigenesis in animals (16, 17). Adipose tissue is considered an endocrine organ that produces adipokines (proinflammatory cytokines) which contribute to high-fat diet-enhanced malignant progression (18,19). We hypothesized that obesity-enhanced progression of luminal B breast cancer is through the up-regulation of inflammation. The present study tested this hypothesis by assessing the effects of a high-fat diet on primary mammary 6279

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“…The analysis of uPA/PAI-1 can thus usefully supplement the information gained from conventional clinical-pathological parameters in the decision for or against adjuvant chemotherapy in cases of hormone-receptor-positive, Her2/neu-negative breast carcinomas [27], even before a multigene test has to be arranged. A further aspect is the difference in cost which can be seen as an additional argument in favour of uPA/PAI-1 testing.…”

Section: Discussionmentioning

confidence: 99%

“…According to the guidelines of the American Society of Clinical Oncology ( ASCO), the levels of uPA and PAI-1 can be drawn upon for the decision for or against adjuvant chemotherapy; this is not recommended for Ki67 alone [ 26 ]. The analysis of uPA/PAI-1 can thus usefully supplement the information gained from conventional clinical-pathological parameters in the decision for or against adjuvant chemotherapy in cases of hormone-receptor-positive, Her2/neu-negative breast carcinomas [ 27 ], even before a multigene test has to be arranged. A further aspect is the difference in cost which can be seen as an additional argument in favour of uPA/PAI-1 testing.…”

Section: Discussionmentioning

confidence: 99%

Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array

et al. 2018

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BackgroundConventional parameters including Ki67, hormone receptor and Her2/neu status are used for risk stratification for breast cancer. The serine protease urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumour invasion and metastasis. Increased concentrations in tumour tissue are associated with more aggressive potential of the disease. Multigene tests provide detailed insights into tumour biology by simultaneously testing several prognostically relevant genes. With OncotypeDX®, a panel of 21 genes is tested by means of quantitative real-time polymerase chain reaction.The purpose of this pilot study was to analyse whether a combination of Ki67 and uPA/PAI-1 supplies indications of the result of the multigene test.MethodsThe results of Ki67, uPA/PAI-1 and OncotypeDX® were analysed in 25 breast carcinomas (luminal type, pT1/2, max pN1a, G2). A statistical and descriptive analysis was performed.ResultsWith a proliferation index Ki67 of < 14%, the recurrence score (RS) from the multigene test was on average in the low risk range, with an intermediate RS usually resulting if Ki67 was > 14%. Not elevated values of uPA and PAI-1 showed a lower rate of proliferation (average 8.5%) than carcinomas with an increase of uPA and/or PAI-1 (average 13.9%); p = 0.054, Student’s t-test. When Ki67 was > 14% and uPA and/or PAI-1 was raised, an intermediate RS resulted. These differences were significant when compared to cases with Ki67 < 14% with non-raised uPA/PAI-1 (p < 0.03, Student’s t-test). Without taking into account the proliferative activity, an intermediate RS was also verifiable if both uPA and PAI-1 showed raised values.ConclusionA combination of the values Ki67 and uPA/PAI-1 tended to depict the RS to be expected. From this it can be deduced that an appropriate analysis of this parameter combination may be undertaken before the multigene test in routine clinical practice. The increasing cost pressure makes it necessary to base the implementation of a multigene test on ancillary variables and to potentially leave it out if not required in the event of a certain constellation of results (Ki67 raised, uPA and PAI-1 raised).

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Potential clinical relevance of uPA and PAI-1 levels in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up

Cited by 9 publications

References 38 publications

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

High-fat Diet Enhances Mammary Tumorigenesis and Pulmonary Metastasis and Alters Inflammatory and Angiogenic Profiles in MMTV-PyMT Mice

Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array

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