Rakha EA, El-Sayed ME, Lee AH, et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma

Department of Histopathology, School of Molecular Medical Sciences, Division of Epidemiology and Public Health, University of Nottingham, Nottingham City Hospital NHS Trust, Hucknall Rd, Nottingham, NG5 1PB United Kingdom.
Journal of Clinical Oncology (Impact Factor: 18.43). 08/2008; 26(19):3153-8. DOI: 10.1200/JCO.2007.15.5986
Source: PubMed


The three strongest prognostic determinants in operable breast cancer used in routine clinical practice are lymph node (LN) stage, primary tumor size, and histologic grade. However, grade is not included in the recent revision of the TNM staging system of breast cancer as its value is questioned in certain settings.
This study is based on a large and well-characterized consecutive series of operable breast cancer (2,219 cases), treated according to standard protocols in a single institution, with a long-term follow-up (median, 111 months) to assess the prognostic value of routine assessment of histologic grade using Nottingham histologic grading system.
Histologic grade is strongly associated with both breast cancer-specific survival (BCSS) and disease-free survival (DFS) in the whole series as well as in different subgroups based on tumor size (pT1a, pT1b, pT1c, and pT2) and LN stages (pN0 and pN1 and pN2). Differences in survival were also noted between different individual grades (1, 2, and 3). Multivariate analyses showed that histologic grade is an independent predictor of both BCSS and DFS in operable breast cancer as a whole as well as in all studied subgroups.
Histologic grade, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive breast cancer and should be incorporated in breast cancer staging systems.

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    • "BC patients were further stratified into two subgroups; those in early stages with no distant metastases (stages I and II; n = 80, mean age 50.1 ± 8.6 years) and a group in late stages of BC with invasive behavior and distant metastases (stages III and IV; n = 70, mean age 52.4 ± 12.5). BC was diagnosed based on the pathological examination and the relevant stage was assigned according to the TNM classification of the Sixth Edition of the American Joint Committee on Cancer (AJCC) Manual for Staging of Cancer (Singletary and Connolly, 2006) and graded by the Nottingham grading system (Rakha et al., 2008). There was no presurgical treatment of chemotherapy, radiotherapy, endocrine therapy or biotherapy. "
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    ABSTRACT: This study aimed to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels in breast cancer (BC) in the Egyptian population to clarify their role in relation to BC. A group of 300 females was recruited in this study; of these 150 unrelated patients with different stages of BC and 150 age-matched healthy controls. Plasma TAFI Ag was measured by ELISA and TAFI Thr325Ile (rs1926447) polymorphism was genotyped using TaqMan single nucleotide polymorphism (SNP) genotyping assay. The results showed the genotypes of the minor allele; Thr/Ile (CT) and Ile/Ile (TT) were significantly more frequent in patients compared to control group (50.0% and 22.0% vs. 42.0% and 13.3%, respectively) and were also associated with BC susceptibility [OR = 1.9 and 2.6; 95% CI: (1.1–3.3) and (1.3–5.5), respectively P = 0.01]. Ile325 allele carriers were more frequent in cases than in controls (47.0% vs. 34.0%) [OR = 1.7, (95% CI = 1.2–2.4), P = 0.001]. However, TAFI Thr325Ile polymorphism was not associated with BC stage or other clincopathological characteristics. TAFI Ag levels were correlated with advanced stages of BC, poor prognosis and risk of recurrence (P = 0.02, P = 0.04 and P < 0.001, respectively) and Thr325Ile SNP was significantly correlated with TAFI antigen levels with the C/C genotype corresponding to the highest and the T/T genotype to the lowest TAFI antigen levels (P < 0.001) in the study groups. In conclusion, this study showed for the first time that TAFI Thr325Ile polymorphism could have a contribution to BC susceptibility in our population. Furthermore, high TAFI plasma levels may serve as a predictor of poor prognosis in patients with BC.
    Meta Gene 06/2015; 4. DOI:10.1016/j.mgene.2015.03.004
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    • "It is generally known that prognosis and treatment of patients with breast carcinoma, NST, are dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor (ER), progesterone receptor (PR), overexpression of human epidermal growth factor receptor 2 HER-2), and proliferation index determined by Ki-67 [1-16]. "
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    ABSTRACT: Background Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index. Methods Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection. Results Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups. Conclusions These data confirm that the original, three-tiered NPI statistically correlates with the expression of prognostic immunohistochemical markers in breast carcinoma NST.
    World Journal of Surgical Oncology 08/2014; 12(243). DOI:10.1186/1477-7819-12-243 · 1.41 Impact Factor
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    • "aAccording to the Ellis and Elston grading system [23]. "
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    ABSTRACT: Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors. Data from consecutive breast cancer patients receiving chemotherapy with 4-6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles. Overall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65;0.93]) and haemoglobin (OR = 0.81 [0.67;0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04;43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01;1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03;3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13;5.44]) in FGFR4. Lower height (OR = 0.62 [0.41;0.92]) increased risk of FN in the first cycle. Both established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings.
    BMC Cancer 03/2014; 14(1):201. DOI:10.1186/1471-2407-14-201 · 3.36 Impact Factor
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