Survival of invasive breast cancer according to the Nottingham Prognostic Index in cases diagnosed in 1990–1999

Blamey, R.W.; Ellis, Ian O.; Pinder, Sarah; Lee, Andrew; Macmillan, R. Douglas; Morgan, D.A.L.; Robertson, J. F. R.; Mitchell, Marci R.; Ball, Graham; Haybittle, J. L.; Elston, C. W.

doi:10.1016/j.ejca.2007.01.016

Cited by 187 publications

(154 citation statements)

References 22 publications

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“…NPI was computed from the above mentioned tumour characteristics, using the formula NPI = 0.2 9 T + N (1-3) + G (1-3) where T is the maximum diameter (in cm), N the number of lymph nodes involved (1 = no axillary lymph nodes involved; 2 = 1-3 axillary lymph nodes involved; 3 = more than 3 axillary lymph nodes involved), and G histological grade (1-3: good, moderate, poorly differentiated). The patients are grouped into three prognostic risk categories for relapse according to the NPI results: 1 = low risk, with NPI equal to or less than 3.4; 2 = medium risk, with NPI between 3.4 and 5.4; 3 = high risk, with NPI over 5.4 [34]. NPI could not be calculated in cases when no axillary lymph node dissection was performed (n = 31).…”

Section: Methodsmentioning

confidence: 99%

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

Brouckaert

Pintens

Belle

et al. 2008

Breast Cancer Res Treat

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Introduction Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the shortterm disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype. Patients and methods Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer patients primary operated at our institution between 2000 and 2005. Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 -(PPN), ER + PR -HER-2 -(PNN), ER + PR + HER-2 + (PPP), ER -PR -HER-2 -(NNN), ER -PR -HER-2 + (NNP), and ER + PR -HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy. Results Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI. Conclusion It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.

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Section: Methodsmentioning

confidence: 99%

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

Brouckaert

Pintens

Belle

et al. 2008

Breast Cancer Res Treat

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“…[4][5][6][7][8][9] Histological grade is a measurement of the intrinsic biological features of cancers, which, based on the assessment of the degree of differentiation (gland formation and nuclear pleomorphism) and proliferative activity, is a morphological reflection of the perceived aggressiveness of tumors. 9,10 The prognostic value of the modified combined histological (Nottingham) grade has been established and validated in multiple large independent studies [11][12][13][14][15][16][17][18][19][20][21] and has been incorporated into prognostic algorithms [22][23][24] and clinical guidelines. 25 Pathologists have also identified specific architectural and cytological patterns the constellation of which defines special types of breast carcinoma.…”

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confidence: 99%

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

et al. 2012

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Oncotype DX is an RT-PCR-based 21-gene assay validated to provide prognostic and predictive information in the form of a Recurrence Score in patients with estrogen receptor-positive, lymph node-negative breast cancer. Although the Recurrence Score was shown to correlate with several histopathological tumor features, there is a significant proportion of cases showing an apparent discrepancy between Recurrence Score and risk estimates based on the traditional clinicopathological tumor features. In this study, we tested whether a proliferating, cellular stroma and/or admixed inflammatory cells may result in an artificially increased Recurrence Score in low-grade invasive breast cancers. We analyzed the histopathological features in 141 low-grade invasive breast carcinomas, including 41 special type (tubular, cribriform and mucinous) carcinomas, with available Recurrence Score. The tumor stroma was evaluated for increased cellularity and presence of inflammatory cells. Double immunohistochemical stains for pancytokeratin and Ki-67 was performed to assess the cell proliferation in tumor vs stromal/inflammatory cells. The clinicopathological features of tumors with Recurrence Score o18 (low risk) were compared with those with Recurrence Score Z18 (intermediate/high risk). Carcinomas associated with Recurrence Score Z18 showed lower progesterone receptor immunoreactivity, increased stromal cellularity and presence of inflammatory cells associated with the tumor. Double immunohistochemical stains showed significantly increased proliferation in stromal/inflammatory cells compared with carcinoma cells in cases associated with Recurrence Score Z18. A Ki-67-positive stromal/ tumor cells ratio of 41 predicted Recurrence Score Z18 with an area under the curve of 0.8967 on receiver operator curve analysis (Po0.0001). Our results suggest that the presence of increased stromal cellularity and/ or associated inflammatory cells in low-grade invasive breast carcinomas may contribute to an apparently increased risk of recurrence according to Oncotype DX Recurrence Score. Careful assessment and correlation with histopathological features in such cases may help in determining the appropriate patient management.

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“…25,29,35 Specifically, patients with breast cancers in the excellent and good Nottingham Prognostic Index groups (104 of 106 cases in this study) were reported to have excellent (96 ± 2 and 93 ± 2%, respectively) 10-year survival rates. 24 Several other large studies have also shown that patients with early stage, lowgrade invasive breast carcinoma have an excellent outcome with over 95% survival. [35][36][37] Indeed, we did not observe any recurrence in our series of lowgrade, early stage breast cancers, although the mean follow-up time was relatively short (54.3 months).…”

Section: Discussionmentioning

confidence: 97%

“…The Recurrence Score is based on expression levels of genes related to hormone receptor/HER2 signaling and cell proliferation to predict a 10-year distant recurrence risk as a continuous variable, assuming that patients receive adjuvant hormonal manipulation. It is also subdivided into three risk categories: low (o18), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and high (430) scores.…”

mentioning

confidence: 99%

“…Based on the Nottingham Prognostic Index, 91, 13 and 2 cases were considered to have an expected excellent (r2.4), good (42.4 butr3.4) and moderate prognosis (43.4), respectively. As both patients in the excellent and good prognostic groups were reported to have excellent 10-year survival (96 ± 2% and 93 ± 2%, respectively), 24 these groups were combined for statistical analysis. At a mean The tumor tissue block used for Oncotype DX testing was used for immunohistochemical and Mammostrat assays in each case.…”

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confidence: 99%

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Comparison of Oncotype DX and Mammostrat risk estimations and correlations with histologic tumor features in low-grade, estrogen receptor-positive invasive breast carcinomas

et al. 2013

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associated with increased stromal cellularity, presence of inflammatory cells and increased proliferation in stromal/inflammatory cells, compared with concordant cases showing low risk by both assays. Our results suggest that low-grade ER-positive breast carcinomas with increased stromal/ inflammatory cell proliferation may show an apparent increased risk of distant recurrence as assessed by Oncotype DX, which uses RNA extracted from a mixture of tumor and stromal/inflammatory cells in the assay. Mammostrat, which examines cancer cells only, may provide a better estimation of likely tumor behavior in a subgroup of low-grade breast carcinomas.

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Survival of invasive breast cancer according to the Nottingham Prognostic Index in cases diagnosed in 1990–1999

Cited by 187 publications

References 22 publications

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

Comparison of Oncotype DX and Mammostrat risk estimations and correlations with histologic tumor features in low-grade, estrogen receptor-positive invasive breast carcinomas

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