Prognostic and Predictive value of the Urokinase-Type Plasminogen Activator (uPA) and Its Inhibitors PAI-1 and PAI-2 in Operable Breast Cancer

2003 ◽  
Vol 18 (2) ◽  
pp. 106-115 ◽  
Author(s):  
T. Cufer ◽  
S. Borstnar ◽  
I. Vrhovec
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Early Breast Cancer ◽  
Systemic Therapy ◽  
Predictive Value ◽  
Serine Proteases ◽  
Univariate Analysis ◽  
Adjuvant Hormone Therapy ◽  
Pai 1 ◽  
Risk Of Relapse

The present study on the prognostic and predictive value of serine proteases was conducted in 460 early breast cancer patients mostly treated with some kind of adjuvant systemic therapy: 156 received chemotherapy, 141 hormone therapy and 111 a combination of both. Already in univariate analysis PAI-1 was the only proteolytic factor with a significant impact on DFS, which was retained in multivariate analysis (p=0.020); PAI-2 showed borderline significance in univariate analysis (p=0.0503) and uPA did not present as a significant prognostic factor for DFS in our patient series. In a separate univariate analysis of DFS on patient subgroups defined by adjuvant systemic therapy, a higher risk of relapse associated with higher uPA and PAI-1 levels was found in the subgroup of patients who did not receive any treatment; this difference did not reach the level of significance, probably due to the small number (n=52) of patients in this group (HR 1.37; p=0.71 and HR 2.14; p=0.321, respectively). A higher risk of relapse was also found in the subgroup of patients treated with adjuvant chemotherapy (HR 1.44; p=0.381 and HR 2.48; p=0.003, respectively). In contrast, the bad prognostic impact of high uPA and PAI-1 levels was lost in the subgroup of patients treated with adjuvant hormone therapy (HR 0.79; p=0.693 and HR 0.26; p=0.204, respectively). The same observations were made for the uPA/PAI-1 combination. Our study confirmed the prognostic value of serine proteases in early breast cancer. In addition, it pointed to a possible predictive value of these tumor markers for response to adjuvant hormone therapy with tamoxifen, which should be confirmed in further studies.

CDK2 and CDK1 specific activities: A novel prognostic indicator in early breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10592-10592
Author(s):  
S. Kim ◽  
N. Masuda ◽  
H. Inaji ◽  
K. Yoshidome ◽  
M. Tsujimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Specific Activity ◽  
Univariate Analysis ◽  
Menopausal Status ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Cycle Phase ◽  
Adjuvant Hormone Therapy ◽  
Node Negative

10592 Background: Cyclin-dependent kinases (CDKs) are expressed almost constantly but their activities change according to cell cycle phase. We studied the specific activity (SA; activity/expression) of CDKs to accurately evaluate their role in cell proliferation. We focused on the ratio of CDK2 SA to CDK1 SA because this ratio has been associated with rapid tumor growth in human breast cancer xenografts. Our goal was to investigate the prognostic significance of CDK2/1 ratio in node-negative breast cancer. Methods: We used a novel assay to measure SAs of CDK2 and CDK1 in 365 primary breast tumors. All tumors were histologically confirmed invasive breast cancer without lymph node involvement. The primary endpoint was relapse-free survival (RFS). Cut-off values for CDK2/1 ratio were defined as those points that best discriminated groups according to RFS. Tumors were grouped as low (136pts), intermediate (84pts), and high (145pts) CDK2/1 ratio. The median follow-up was 59 months (range 4–102). Results: Pts characteristics are described as follows: menopausal status: pre- 42%, post- 58%; tumor size: =20mm 48%, >20mm 52%; histologic grade (HG): I 28%, II 47%, III 23%; ER: (+) 57%, (-) 42%; PR: (+) 51%, (-) 48%. Pts with HG III or high CDK2/1 ratio showed significantly lower 5y-RFS rates than those with HG I/II or low/intermediate CDK2/1 ratio, respectively (HG: I 97%, II 91%, III 85%, P=0.040; CDK2/1 ratio: low 97%, intermediate 92%, high 85%, P=0.017). In univariate analysis, PR (- vs +, P=0.088) had a tendency to associate with relapse, and HG (III vs I, P=0.024) and CDK2/1 ratio (high vs low, P=0.011) also had a significant correlation with relapse. However, only CDK2/1 ratio showed a significant independent prognostic indicator in multivariate analysis (hazard ratio 2.86, 95% CI 1.25–6.58, P=0.01). More important, among women (n=185) with hormone receptor (HR) positive disease given adjuvant hormone therapy alone, who have had no useful factors to predict their outcomes, high CDK2/1 ratio was also associated with worse prognosis than low CDK2/1 ratio (5y-RFS 84% vs 100%, P=0.007). Conclusions: For patients with node- negative disease, especially those with HR positive tumors given adjuvant hormone therapy alone, the CDK2/1 ratio might be useful as a routine laboratory test to predict outcome. No significant financial relationships to disclose.

scholarly journals Is the extension of adjuvant hormone therapy for breast cancer justified?

2020 ◽  
pp. 74-79
Author(s):  
V. F. Semiglazov ◽  
V. S. Apollonova
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Hormone Therapy ◽  
Tumor Grade ◽  
Low Risk ◽  
Tamoxifen Treatment ◽  
Proliferation Index ◽  
Adjuvant Hormone Therapy ◽  
Risk Of Relapse

In practice, all patients with ER (+) primary breast cancer should conduct adjuvant hormone therapy to suppress the growth of tumors stimulated by estrogens. Five-year tamoxifen treatment reduces breast cancer mortality for 30%, and aromatase inhibitors (for postmenopausal women) reduces it by up to 40%. After five years, long-term relapses still occurred, the risk of which can be reduced by the expansion of adjuvant hormone therapy for more than 5 years. At the population level, the treatment can show relatively moderate and sometimes toxic effects; therefore, it is extremely important for modern clinical practice to identify patients with risk of relapse within the first five years small enough for the therapy to be safely canceled for this period, as well as patients with a risk of relapse high enough to justify a longer treatment. Currently, little data is available from clinical trials regarding the second problem. Recent EBCTCG studies have consistently shown a risk of relapse within 5–20 years in all patient groups. However, the risk varies greatly depending on the size of the tumor and the status of the lymph nodes. The tumor grade (G) and the proliferation index (Ki67), supplementing the information on the TN stage, demonstrate a high degree of correlation between each other. The only patients who have a relatively low frequency of long-term recurrence (which allows them to be assigned to a very low risk group) are patients with a low tumor grade pT1N0. Prognostic molecular signatures have been proven to be clinically useful (in addition to clinical and morphological characteristics) in identifying patients with an extremely low risk of relapse who can safely avoid chemotherapy. In clinical trials of adjuvant hormone therapy with a long follow-up period (up to 20 years), a delayed (over five years) recurrence of estrogen-receptor-positive (ER+) breast cancer was noted. Based on these observations, a number of researchers offer longer hormone therapy (exceeding the five-year standard).

scholarly journals Identification of Subgroups of Early Breast Cancer Patients at High Risk of Nonadherence to Adjuvant Hormone Therapy: Results of an Italian Survey

2015 ◽  
Vol 15 (2) ◽  
pp. e131-e137 ◽  
Author(s):  
Nicola Tinari ◽  
Caterina Fanizza ◽  
Marilena Romero ◽  
Elisabetta Gambale ◽  
Luca Moscetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Hormone Therapy ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Breast Cancer Patients ◽  
Adjuvant Hormone Therapy ◽  
Italian Survey
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