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.

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.

Influence of Endocrine-Related Factors on Response to Perioperative Chemotherapy for Patients With Node-Negative Breast Cancer

2001 ◽  
Vol 19 (21) ◽  
pp. 4141-4149 ◽  
Author(s):  
Marco Colleoni ◽  
Shari Gelber ◽  
Alan S. Coates ◽  
Monica Castiglione-Gertsch ◽  
Richard D. Gelber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Steroid Hormone ◽  
Menopausal Status ◽  
Prognostic Significance ◽  
Steroid Hormone Receptors ◽  
Perioperative Chemotherapy ◽  
Primary Tumors ◽  
Node Negative ◽  
Node Negative Breast Cancer

PURPOSE: We investigated tumor- and patient-related features that might influence the response to perioperative chemotherapy (PeCT) compared with no adjuvant therapy for patients with node-negative breast cancer. PATIENTS AND METHODS: A total of 1,275 patients were randomized to either no adjuvant treatment (427 patients) or PeCT (848 patients). The following variables thought to have prognostic significance were evaluated: grade, tumor size, estrogen (ER) and progesterone receptor (PgR) content (absent; low, 1 to 9 fmol/mg cytosol protein; or positive, ≥ 10 fmol/mg cytosol protein), c-erbB-2 overexpression, menopausal status, and age. Cox proportional hazards regression models were used to assess the relative influence of these factors to predict the effect of PeCT on disease-free survival (DFS). Median follow-up was 13.5 years. RESULTS: The 10-year DFS percentage for 692 premenopausal patients did not significantly differ between the PeCT and no-adjuvant-treatment groups: 61% and 59%, respectively (relative risk [RR], 0.95; 95% confidence interval [CI], 0.75 to 1.20; P = .70). No predictive factors were identified. For 583 postmenopausal patients, 10-year DFS percentages for the groups were 63% and 58%, respectively (RR, 0.75; 95% CI, 0.58 to 0.93; P = .03). The absence of expression of ER, PgR, or both ER and PgR was the most important factor predicting improved outcome with PeCT among postmenopausal patients. The 10-year DFS percentages were 85% and 53% for the steroid hormone receptor–absent cohort of treated and untreated patients, respectively (RR, 0.18; 95% CI, 0.06 to 0.49; P = .0009). CONCLUSION: The role of PeCT should be explored for patients whose primary tumors do not express steroid hormone receptors, because it is likely that early initiation of treatment is exclusively relevant for such patients.

Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.

1990 ◽  
Vol 8 (9) ◽  
pp. 1457-1465 ◽  
Author(s):  
A K Lee ◽  
R A DeLellis ◽  
M L Silverman ◽  
G J Heatley ◽  
H J Wolfe
Keyword(s):  
Blood Vessel ◽  
Menopausal Status ◽  
False Negative ◽  
Prognostic Significance ◽  
Radical Mastectomy ◽  
Prognostic Indicator ◽  
Blood Vessel Invasion ◽  
Carcinoma Of The Breast ◽  
Node Negative ◽  
Vessel Invasion

The prognostic significance of intramammary lymphatic and blood vessel invasion was evaluated in a retrospective series of 221 patients with node-negative carcinoma of the breast treated with modified radical mastectomy. To facilitate identification of lymphatic and blood vessel invasion, the tumors were studied with an immunohistochemical technique using antibodies to endothelial markers. Peritumoral lymphatic and blood vessel invasion (PLBI) (encompassing both lymphatic and blood vessel invasion) was an adverse prognostic indicator independent of menopausal status, tumor size, and other histologic variables. Recurrence of disease and death resulting from carcinoma were significantly higher for patients with PLBI-present (+) tumors compared with patients with PLBI-absent (-) tumors (P less than .0001). The risk of recurrence for patients with PLBI+ tumors was 4.7 times that for their PLBI- counterparts. The presence of intratumoral lymphatic and blood vessel invasion (ILBI) is less important because few examples were found without concomitant PLBI. When PLBI was separated into lymphatic invasion and blood vessel invasion individually, the prognostic significance was retained in both groups. The immunohistochemical approach reduced both false-negative and false-positive observations and identified about 40% of PLBI that would have been missed by routine histologic examination alone. The presence of PLBI appears to be a potentially useful discriminant in predicting the outcome of patients with node-negative carcinoma of the breast.

Prognostic significance of body mass index in breast cancer patients with hormone receptor-positive tumours after curative surgery

2013 ◽  
Vol 36 (6) ◽  
pp. 297 ◽  
Author(s):  
Peng Xing ◽  
Ji-Guang Li ◽  
Feng Jin ◽  
Ting-Ting Zhao ◽  
Qun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
Hormone Receptor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Axillary Lymph ◽  
Nodal Stage ◽  
Hormone Receptor Positive ◽  
High Bmi

Purpose: Obesity has been recognized as a significant risk factor for postmenopausal breast cancer. The aim of this study is to investigate the prognostic significance of body mass index (BMI) in hormone receptor-positive, operable breast cancer. Methods: In this retrospective cohort study, 1,192 consecutive patients with curative resection of primary breast cancer were enrolled. Patients were assigned to two groups according to BMI: normal or underweight (BMI < 23.0 kg/m2) and overweight or obese (BMI ≥23.0 kg/m2). Associations among BMI and clinicopathological characteristics and prognosis of patients were assessed. Results: A high BMI was significantly (P < 0.01) correlated with age, nodal stage, ALNR, ER positivity, PR positivity and menopausal status at diagnosis. Univariate analysis revealed that BMI, pathologic T stage, nodal stage, axillary lymph node ratio (ALNR) and adjuvant radiotherapy history were significantly (P < 0.05) associated with disease-free survival and overall survival, irrespective of tumour hormone receptor status. Multivariate analysis revealed BMI as an independent prognostic factor in all cases and in hormone receptor-positive cases. Conclusion: A high BMI (≥23.0 kg/m^2) is independently associated with poor prognosis in hormone receptor-positive breast cancer.

scholarly journals Socioeconomic factors associated with adjuvant hormone therapy use in older breast cancer survivors

Cancer ◽  
2010 ◽  
Vol 117 (2) ◽  
pp. 398-405 ◽  
Author(s):  
Tina W. F. Yen ◽  
Linda K. Czypinski ◽  
Rodney A. Sparapani ◽  
Changbin Guo ◽  
Purushottam W. Laud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Socioeconomic Factors ◽  
Hormone Therapy ◽  
Breast Cancer Survivors ◽  
Adjuvant Hormone Therapy ◽  
Factors Associated

Adjuvant Hormone Therapy for Breast Cancer

2019 ◽  
pp. 479-487
Author(s):  
Andrea K. Shimada ◽  
João Victor Machado Alessi ◽  
Bruna Zucchetti ◽  
Artur Katz
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Adjuvant Hormone Therapy

scholarly journals Long-term prognostic significance of HER-2/neu in untreated node-negative breast cancer depends on the method of testing

2005 ◽  
Vol 7 (2) ◽  
Author(s):  
Marcus Schmidt ◽  
Barbara Lewark ◽  
Nikolai Kohlschmidt ◽  
Christiane Glawatz ◽  
Erik Steiner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Her 2

scholarly journals Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes

2009 ◽  
Vol 27 (8) ◽  
pp. 1160-1167 ◽  
Author(s):  
Joel S. Parker ◽  
Michael Mullins ◽  
Maggie C.U. Cheang ◽  
Samuel Leung ◽  
David Voduc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Risk Score ◽  
Tumor Size ◽  
Pathologic Complete Response ◽  
Prognostic Significance ◽  
Intrinsic Subtype ◽  
Cancer Prognosis ◽  
Intrinsic Subtypes ◽  
Node Negative

Purpose To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like. Methods A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. Results The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. Conclusion Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.

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