Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole

Viale, Giuseppe; Giobbie‐Hurder, Anita; Regan, Meredith M.; Coates, Alan S.; Mastropasqua, Mauro G.; Dell’Orto, Patrizia; Maiorano, Eugenio; MacGrogan, Gaëtan; Braye, Stephen; Öhlschlegel, Christian; Neven, Patrick; Orosz, Zsolt; Olszewski, Wojciech; Knox, Fiona; Thürlimann, Beat; Price, Karen N.; Castiglione‐Gertsch, Monica; Gelber, Richard D.; Gusterson, Barry A.; Goldhirsch, Aron

doi:10.1200/jco.2008.17.0829

Cited by 305 publications

(233 citation statements)

References 30 publications

(10 reference statements)

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“…It was also decided not to use the best, but most likely overfitted, cut-off for Ki-67 but the one calculated from 2685 patients by Viale et al (2008) 11% . The same one was used for UBE2C.…”

Section: Discussionmentioning

confidence: 99%

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer

et al. 2009

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BACKGROUND:We recently identified and validated UBE2C RNA as a prognostic marker in 252 node-positive (N þ ) breast cancers by means of a microarray study. The aim of this study was to validate UBE2C protein as a prognostic marker in N þ breast cancer by immunohistochemistry (IHC). METHODS: To this end, 92 paraffin-embedded blocks were used. The impact of UBE2C IHC value on metastasis-free survival (MFS) and overall survival (OS) was evaluated and compared with Ki-67 and Nottingham prognostic index (NPI) performances. RESULTS: In accordance with genomic data, UBE2C IHC had a significant impact both on MFS and OS (hazard ratio ¼ 6.79 -P ¼ 0.002; hazard ratio ¼ 7.14 -P ¼ 0.009, respectively). Akaike information criterion proved that the prognostic power of UBE2C IHC was stronger than that of Ki-67 (and close to that of NPI). Furthermore, multivariate analyses with NPI showed that, contrary to Ki-67 IHC, UBE2C IHC remained an independent factor, both for MFS (adjusted P ¼ 0.02) and OS (adjusted P ¼ 0.04). CONCLUSION: We confirmed that UBE2C protein measured by IHC could be used as a prognostic marker in N þ breast cancer. The potential predictive interest of UBE2C as a marker of proteasome activity needs further investigations.

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Section: Discussionmentioning

confidence: 99%

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer

et al. 2009

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“…Nuclear positivity of Ki67 protein is an indication of cell proliferation [6,7] and it has long been reported as a prognostic marker in breast cancer (BC) [8][9][10][11]. There is evidence that tumours with higher expression levels of Ki67 respond better to adjuvant chemotherapy than those tumour having low levels of Ki67 [11,12].…”

Section: Introductionmentioning

confidence: 99%

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer

Aleskandarany

Green

Ashankyty

et al. 2016

Breast Cancer Res Treat

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In breast cancer (BC), the prognostic value of Ki67 expression is well-documented.Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour quadrants and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression (hot) spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), coefficient of variation and correlation coefficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (p<0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r=0.98, p <0.001). In summary, assessment of Ki67 expression using HS scoring method on a fullface BC tissue section can represent the primary tumour growth fraction that likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.3

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“…Reports on the connection with prognosis have been particularly numerous 8,9 , and a near-consensus on this has been reached. The Ki-67 LI was also signi cantly correlated with relapse and prognosis in the present study.…”

Section: Characteristics Of Ki-67mentioning

confidence: 99%

“…Jones et al 24 reported that 400 magnification in 10 elds, counting at least 1000 tumor cells, is essential. However, this method is complex and time-consuming in actual clinical practice, so some facilities use automated measurements assisted by analysis software 8 , and this technique is also reported to be useful for needle biopsy tissue 25 . However, this automated technique tends to count some nontumor cells, such as lymphocytes, thus affecting its accuracy.…”

Section: Determination Of the Ki-67 Labeling Indexmentioning

confidence: 99%

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Significance of Ki-67 Expression and Risk Category (St. Gallen 2007) in Elderly Breast Cancer Patients, with Emphasis on the Need for Postoperative Adjuvant Therapy

Matsuo

Date

Sawada

et al. 2011

Showa Univ J Med Sci

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: Breast cancer is increasing in the elderly. Although elderly breast cancer patients frequently receive less invasive therapy, its appropriateness is debatable. Ki-67 expression is a controversial prognostic factor and predictor of the ef cacy of postoperative adjuvant therapy. This study investigated the value of the Ki-67 labeling index LI in elderly breast cancer patients, especially with respect to adjuvant therapy. This retrospective study investigated 82 primary breast cancer patients aged ≥ 70 years who underwent surgery between 1995 and 2005. Their clinicopathological ndings were reviewed and their Ki-67 LIs were determined. The patients mean age was 78 years, the mean observation period was 53.8 months, and 60 patients 73.2% underwent adjuvant therapy. The St. Gallen 2007 risk category and the Ki-67 LI mean, 15.3% were both signi cantly correlated with relapse and prognosis. In the 31 cases with a low Ki-67 LI 10% , 1 patient who underwent adjuvant treatment relapsed, but there were no deaths. Among the intermediateand high-risk patients, Ki-67 was low in 15 ; 1 patient who underwent adjuvant treatment relapsed, but there were no deaths. For elderly breast cancer patients aged ≥ 70 years categorized low risk by St. Gallen 2007 or with a low Ki-67 LI, the risk of relapse and death appears to be low regardless of adjuvant therapy. Though further investigation is needed to determine a method of measuring the Ki-67 LI and determining a cut-off value, our ndings suggest that the Ki-67 LI helps with the selection of adjuvant therapy in elderly patients.

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Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole

Cited by 305 publications

References 30 publications

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer

Significance of Ki-67 Expression and Risk Category (St. Gallen 2007) in Elderly Breast Cancer Patients, with Emphasis on the Need for Postoperative Adjuvant Therapy

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