Low Proliferative Rate of Invasive Node-Negative Breast Cancer Predicts for a Favorable Outcome: A Prospective Evaluation of 669 Patients

Jones, Stephen E.; Clark, Gary M.; Koleszar, Sherry; Ethington, Gaby; Mennel, Robert G.; Paulson, Scott; Brooks, Barry Don; Kerr, R. C.; Denham, Claude; Savin, Michael A.; White, Charles S.; Blum, Joanne L.; Kirby, Robert; Stone, Marvin J.; Pippen, John; Kitchens, Lloyd W.; George, Timothy; Cooper, Barry; Peters, G.; Knox, Sally M.; Grant, Michael D.; Cheek, Harold; Jones, Ronald C.; Kuhn, Joseph A.; Lieberman, Zelig H.; Savino, Daniel A.; Rietz, Charles

doi:10.3816/cbc.2001.n.005

Cited by 18 publications

(7 citation statements)

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“…Ki-67 is correlated with proliferation and has been shown to be correlated with the prognosis of breast cancer patients in several settings, including node-negative disease and in metastatic patients (22)(23)(24)(25). Ki-67 correlates with the growth fraction or S-phase fraction and can be evaluated on small samples in which other methods are not applicable (26).…”

Section: Discussionmentioning

confidence: 99%

BCIRG 001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy

Dumontet

Krajewska

Treilleux

et al. 2010

Clinical Cancer Research

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Purpose: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/ cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for nodepositive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS).Experimental Design: Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, β-tubulin isotypes II, III and IV, τ protein, and detyrosinated α tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique.Results: In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and τ protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas τ protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation.Conclusions: We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters τ protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy. Clin Cancer Res; 16(15); 3988-97. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

BCIRG 001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy

Dumontet

Krajewska

Treilleux

et al. 2010

Clinical Cancer Research

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“…Several reports observed the prognostic value of SPF in breast cancer [93,94]. Low SPF is associated with an excellent prognosis in LN- breast patients [95-97]. Based on the grading efficiency analysis [98] SPF estimation from isolated nuclei may reach efficiencies comparable to that of mitotic counts.…”

Section: Introductionmentioning

confidence: 99%

Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future?

et al. 2006

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Prognosticators evaluating survival in breast cancer vary in significance in respect to lymph node status. Studies have shown e.g. that HER2/neu immunohistochemistry or HER2/neu gene amplification analysis do perform well as prognosticators in lymph node positive (LN +) patients but are less valuable in lymph node negative (LN -) patients. We collected data from different studies and tried to evaluate the relative significance of different prognosticators in LN+/LNpatient groups. In LN+ patients HER2/neu and E-cadherin immunohistochemistry were the statistically most significant prognosticators followed by proliferation associated features (mitotic counts by SMI (standardised mitotic index) or MAI (mitotic activity index), or S-phase fraction). Bcl-2 immunohistochemistry was also significant but p53 and cystatin A had no significance as prognosticators. In LN-patients proliferation associated prognosticators (SMI, MAI, Ki-67 index, PCNA immunohistochemistry, S-phase fraction) are especially valuable and also Cathepsin D, cystatin A, and p53 are significant, but HER2/neu or bcl-2, or E-cadherin less significant or without significance. We find that in studies evaluating single prognosticators one should distinguish between prognosticators suitable for LN+ and LN-patients. This will allow the choice of best prognosticators in evaluating the prospects of the patient. The distinction between LN+ and LNpatients in this respect may also be of special value in therapeutic decisions.

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“…The Ki-67 immunostaining has also been reported to be an independent prognostic factor when compared to nodal status, age and chemotherapy [11] . A low proliferation rate measured by Ki-67 is associated with an excellent prognosis in invasive node-negative breast cancers up to 5 cm in size, regardless of the adjuvant treatment [12] .…”

Section: Introductionmentioning

confidence: 99%

Ki-67, p53, ER Receptors, Ploidy and S Phase as Long-Term Prognostic Factors in T1 Node-Negative Breast Cancer

Railo¹,

Lundin²,

Haglund³

et al. 2007

Tumor Biol

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Background: The aim of the present study was to evaluate a series of biomarkers with regard to long-term prognostic value in patients with T1 (≤2 cm) node-negative breast cancer. Method: The prognostic value of Ki-67, p53, oestrogen receptor (ER) immunohistochemical labelling, flow-cytometric S phase fraction and ploidy was evaluated in 212 patients with pT1N0M0 breast cancer. The median follow-up time was 15.9 years (range 0.2–27.2 years). Results: In an analysis of breast cancer-specific survival up to 5 years, high Ki-67 (≧10%; p = 0.002), high p53 (≧20%; p = 0.01), negative ER (<30%; p = 0.01) as well as aneuploidy of the tumour (p = 0.02) were significant prognostic factors. When the follow-up was extended to 10 years, only Ki-67 (p = 0.03) was significantly associated with outcome and beyond 15 years none of the studied markers provided significant prognostic information when analyzed separately. There was a weak but significant difference in long-term survival when patients with a combination of high Ki-67 (≧10%), high SPF (>3%) and high p53 (≧20%) were compared to patients with other combinations (p = 0.03). Conclusion: According to the results of our series, it seems that several prognostic markers which are associated with short-term survival (≤5 years) in pT1N0M0 breast cancer may not be significant predictors of long-term (>15 years) breast cancer-specific survival.

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Low Proliferative Rate of Invasive Node-Negative Breast Cancer Predicts for a Favorable Outcome: A Prospective Evaluation of 669 Patients

Cited by 18 publications

References 18 publications

BCIRG 001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy

BCIRG 001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy

Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future?

Ki-67, p53, ER Receptors, Ploidy and S Phase as Long-Term Prognostic Factors in T1 Node-Negative Breast Cancer

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