Immunologic Proliferation Marker Ki-S2 as Prognostic Indicator for Lymph Node-Negative Breast Cancer

Rudolph, Pierre; Alm, Per; Heidebrecht, Hans-Jürgen; Bolte, Hendrik; Ratjen, Virgo; Baldetorp, Bo; Fernö, Mårten; Olsson, Håkan; Parwaresch, Reza

doi:10.1093/jnci/91.3.271

Cited by 64 publications

(61 citation statements)

References 37 publications

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“…Although several antibodies are now commercially available to stain Ki-67, anti-MIB-1 is the most frequently used in recent studies (Urruticoechea et al, 2005). In our meta-analysis, antibodies other than anti-MIB-1 and anti-Ki-67 were included, such as anti-Ki-S5 (Rudolph et al, 1999a;Esteva et al, 2004) and anti-Ki-S11 (Rudolph Figure 1 Results of the meta-analysis with all evaluable studies for DFS. A hazard ratio (HR)41 implies a worse DFS for the group with increased Ki-67.…”

Section: Discussionmentioning

confidence: 99%

“…Different antibodies were used through all trials: anti-Ki-67 was used in 24 studies (52.1%), anti-MIB-1 in 24 studies (52.1%), both antibodies were performed in five studies (Keshgegian and Cnaan, 1995;Veronese et al, 1995;Bevilacqua et al, 1996;Querzoli et al, 1996;Billgren et al, 2002), anti-Ki-S5 in two studies (Rudolph et al, 1999a;Esteva et al, 2004) and anti-Ki-S11 in one study (Rudolph et al, 1999b). The different cut-off values used were those of the authors (range: 3.5 -34%).…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

“…Out of the 38 evaluable studies for DFS (10 954 patients), subgroup analysis was possible in 15 studies with node-negative patients (3370 patients) (Sahin et al, 1991;Weikel et al, 1991Weikel et al, , 1995Gaglia et al, 1993;Bevilacqua et al, 1996;Brown et al, 1996;Pierga et al, 1996;Railo et al, 1997;Jansen et al, 1998;Clahsen et al, 1999;Harbeck et al, 1999;Rudolph et al, 1999a;Billgren et al, 2002;Trihia et al, 2003;Erdem et al, 2005), in eight with node-positive patients (1430 patients) (Weikel et al, 1991Gaglia et al, 1993;Pierga et al, 1996;Jansen et al, 1998;Billgren et al, 2002;Trihia et al, 2003;Esteva et al, 2004) and in six with untreated nodenegative patients (736 patients) (Sahin et al, 1991;Weikel et al, 1991;Bevilacqua et al, 1996;Railo et al, 1997;Jansen et al, 1998;Harbeck et al, 1999). Regarding OS (9472 patients), of all 35 studies, subgroup analysis was possible in nine studies with nodenegative patients (1996 patients) (Jensen et al, 1995;Weikel et al, 1995;Bevilacqua et al, 1996;Brown et al, 1996;Domagala et al, 1996;Fresno et al, 1997;Rudolph et al, 1999a;Trihia et al, 2003;Erdem et al, 2005), in four with node-positive patients (857 patients) Domagala et...…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

“…Regarding OS (9472 patients), of all 35 studies, subgroup analysis was possible in nine studies with nodenegative patients (1996 patients) (Jensen et al, 1995;Weikel et al, 1995;Bevilacqua et al, 1996;Brown et al, 1996;Domagala et al, 1996;Fresno et al, 1997;Rudolph et al, 1999a;Trihia et al, 2003;Erdem et al, 2005), in four with node-positive patients (857 patients) Domagala et al, 1996;Gonzalez et al, 2003;Trihia et al, 2003) and in two that included only untreated patients (node-negative and node-positive) (284 patients) (Pinder et al, 1995;Bevilacqua et al, 1996).…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

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Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

et al. 2007

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The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In order to better define the prognostic value of Ki-67/MIB-1, we performed a meta-analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies were identified and 46 studies including 12 155 patients were evaluable for our meta-analysis; 38 studies were evaluable for the aggregation of results for DFS, and 35 studies for OS. Patients were considered to present positive tumours for the expression of Ki-67/MIB-1 according to the cut-off points defined by the authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse in all patients (HR ¼ 1.93 (95% confidence interval (CI): 1.74 -2.14); Po0.001), in node-negative patients (HR ¼ 2.31 (95% CI: 1.83 -2.92); Po0.001) and in node-positive patients (HR ¼ 1.59 (95% CI: 1.35 -1.87); Po0.001). Furthermore, Ki-67/MIB-1 positivity is associated with worse survival in all patients (HR ¼ 1.95 (95% CI: 1.70 -2.24; Po0.001)), node-negative patients (HR ¼ 2.54 (95% CI: 1.65 -3.91); Po0.001) and node-positive patients (HR ¼ 2.33 (95% CI: 1.83 -2.95); Po0.001). Our meta-analysis suggests that Ki-67/ MIB-1 positivity confers a higher risk of relapse and a worse survival in patients with early BC.

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Section: Discussionmentioning

confidence: 99%

Section: Characteristics Of the Studiesmentioning

confidence: 99%

Section: Characteristics Of the Studiesmentioning

confidence: 99%

Section: Characteristics Of the Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

et al. 2007

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“…5,8,[17][18][19][20][21][22] It is also a predictor of better response to chemotherapy. 5,7 Furthermore, as Ki67 is also affordable and easily assessed on paraffin-embedded tumor material, it has been widely used, even though it has not been generally recommended for use by all guidelines, 1,2 as there is no international standardization for the method.…”

mentioning

confidence: 99%

The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer

et al. 2010

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The aim of this study was to evaluate the prognostic value of Ki67 in relation to established prognostic factors in lymph node-negative breast cancer, and furthermore, whether the prognostic impact was dependent on estrogen receptor (ER) status and histological grade. In 200 premenopausal patients, with 5 years of follow-up, Ki67 was determined on tissue microarrays. In univariate analysis, Ki67 (r20 vs 420%) was a prognostic factor for distant disease-free survival (hazard ratio: 2.7, 95% confidence interval: 1.3-5.4, P ¼ 0.005) and overall survival (hazard ratio: 4.9, 95% confidence interval: 1.7-14, P ¼ 0.003). When stratifying for ER status and histological grade, Ki67 was a significant prognostic factor for distant disease-free survival and overall survival only in the ER-positive group, and only in patients with histological grade 2, respectively. In multivariate analysis, human epidermal growth factor receptor 2 and age were independent prognostic factors for distant disease-free survival, whereas Ki67, histological grade, and tumor size were not. Ki67 was, however, an independent prognostic factor in the 87% of the patients who had not received adjuvant medical treatment. Agreement between the three readers was very good (j-values: 0.83-0.88). Furthermore, Ki67 was a significant prognostic factor for all three investigators (hazard ratio: 2.7-3.2). This study shows that Ki67 is a prognostic factor in node-negative breast cancer. It is noteworthy that the prognostic information of Ki67 is restricted to ER-positive patients, and to patients with histological grade 2. Taken together, Ki67, as an easily assessed and reproducible proliferation factor, may be an alternative or complement to histological grade as a prognostic tool and for selection of adjuvant treatment.

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Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: A retrospective multicenter study

et al. 2000

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Among the methodological approaches of tumor proliferation, thymidine kinase (TK) and thymidylate synthase (TS) assays take into account the specific pathways of pyrimidine synthesis. Studies pointing to a prognostic value of TK and TS in breast cancer involved small numbers of patients. We investigated the prognostic value of these enzymes and their combination in a large retrospective multicenter study. Nine hundred eight T1T2, N0N1, M0 primary breast cancer samples (median follow‐up 68 months) were tested. TK and TS were measured in cytosols by using standardized radioenzymatic methods. Although a positive correlation was obtained between TK and TS (p<10−5), major discrepancies were observed in some tumors. High levels of both enzymes were associated with large tumor size, histological grade III and steroid receptor‐negative tumors. Univariate analysis showed that TK, TS and their combination were predictive of poor metastasis‐free (MFS) (p < 10−4; p=0.004; p < 10−4) and disease‐free survival (DFS) (p < 10−4; p=0.007; p=0.0001). TK was selected as an independent factor for MFS in Cox analysis. It was the only variable selected in node‐negative patients. Subgroups with specific outcomes, with possible therapeutic implications, were identified: a) in node‐negative patients not receiving adjuvant treatment, TK values in the 4th quartile were associated with poor MFS (p=0.0002) and DFS (p=0.0005) as compared to the other quartiles; b) in node‐positive patients receiving adjuvant chemotherapy, low levels of both TK and TS were associated with the highest survival rates (MFS: p=0.04; DFS: p=0.03). Int. J. Cancer 87:860–868, 2000. © 2000 Wiley‐Liss, Inc.

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Immunologic Proliferation Marker Ki-S2 as Prognostic Indicator for Lymph Node-Negative Breast Cancer

Cited by 64 publications

References 37 publications

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer

Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: A retrospective multicenter study

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