Dataset Information

Invasive breast cancer: stratification of histological grade by gene-based assays: a still relevant example from an older data set.

ABSTRACT:

Aims

A Netherlands Kanker Institute data set provided the results of gene-based assays (GBAs) and histological grades of 295 patients with invasive breast cancer. Grade is the first prognostic assay available after a cancer diagnosis. Given this time-line of actual practise, the aim was to study how gene-based assays further stratify histologic grade.

Methods and results

Emphasis was placed on evaluation of a simple decision tree and on study of the recurrence score (RS). The decision tree determined three risk stratifications. Tumours that were both intermediate grade (IG) and low-RS were grouped with low grade, and tumours that were IG and high-RS were coupled with high grade. IG and intermediate-RS tumours comprised the third category. Survival analysis was performed with respect to the three stratifications. Cramer's V statistic was used for concordance analysis. The mixed grade-RS classifier showed significant survival stratification (P < 0.00001). The mixed classifier was concordant with the 70-gene assay (Cramer's V = 0.57). Recurrence score alone had a 0.59 Cramer's V with the gene assay. Because two-thirds of tumours were of either low or high grade, concordance was maintained despite the majority of classifications having been determined by grade alone.

Conclusion

There is no compelling reason to test low- and high-grade tumours further by GBAs.

SUBMITTER: Dalton L

PROVIDER: S-EPMC4282326 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Invasive breast cancer: stratification of histological grade by gene-based assays: a still relevant example from an older data set.

Dalton Leslie L

Histopathology 20140806 3

<h4>Aims</h4>A Netherlands Kanker Institute data set provided the results of gene-based assays (GBAs) and histological grades of 295 patients with invasive breast cancer. Grade is the first prognostic assay available after a cancer diagnosis. Given this time-line of actual practise, the aim was to study how gene-based assays further stratify histologic grade.<h4>Methods and results</h4>Emphasis was placed on evaluation of a simple decision tree and on study of the recurrence score (RS). The deci ...[more]

PMID: 24673556

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Project description:BackgroundColorectal cancer (CRC) consists of several histological subtypes that greatly affect prognosis. Venous invasion (VI) has been implicated in the postoperative recurrence of CRC, but the relationship between the VI grade and postoperative recurrence in each histological subtype has not been clarified thus far.MethodsA total of 323 CRCs without distant metastasis at surgery (pathologic stage III or lower), including 152 well-to-moderately differentiated adenocarcinomas (WMDAs), 98 poorly differentiated adenocarcinomas (PDAs), and 64 mucinous adenocarcinomas (MUAs), were analyzed. They were routinely processed pathologically, and VI was graded as follows irrespective of location by elastica van Gieson staining: v0 (none), no venous invasion; v1 (mild), 1-3 invasions per glass slide; v2 (moderate), 4-6 invasions per glass slide; and v3 (severe), ≥ 7 invasions per glass slide. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed.ResultsAll recurrences occurred as distant metastases. Recurrence increased with VI grade in WMDA (v0 11.8%, v1 15.8%, v2 73.9%, v3 75.0%) and MUA (v0 15.2%, v1 30.8%, v2 40.0%). The recurrence rate was relatively high in PDA even with v0 and increased with VI grade (v0 27.8%, v1 32.7%, v2 33.3%, v3 60.0%). VI grade was a significant predictor of recurrence in WMDA but not in PDA and MUA by multivariate analysis. In node-negative (stage II or lower) CRC, the recurrence-free survival (RFS) rate exceeded 90% in v0 and v1 WMDA until postoperative day (POD) 2100 and v0 MUA until POD 1600 but fell below 80% in the other settings by POD 1000. In node-positive (stage III) CRC, the RFS rate fell below 80% in all histological subtypes by POD 1000.ConclusionsVI grade v1 had a similar recurrence rate and RFS as grade v0 and may not warrant adjuvant chemotherapy in node-negative (stage II or lower) WMDA. In addition to node-positive (stage III) CRC, adjuvant chemotherapy may be indicated for node-negative (stage II or lower) CRC when it is WMDA with VI grade v2 or v3, MUA with VI, or PDA.

Project description:BackgroundThe histologic grade (HG) of breast cancer is an established prognostic factor. The grade is usually reported on a scale ranging from 1 to 3, where grade 3 tumours are the most aggressive. However, grade 2 is associated with an intermediate risk of recurrence, and carries limited information for clinical decision-making. Patients classified as grade 2 are at risk of both under- and over-treatment.MethodsRNA-sequencing analysis was conducted in a cohort of 275 women diagnosed with invasive breast cancer. Multivariate prediction models were developed to classify tumours into high and low transcriptomic grade (TG) based on gene- and isoform-level expression data from RNA-sequencing. HG2 tumours were reclassified according to the prediction model and a recurrence-free survival analysis was performed by the multivariate Cox proportional hazards regression model to assess to what extent the TG model could be used to stratify patients. The prediction model was validated in N=487 breast cancer cases from the The Cancer Genome Atlas (TCGA) data set. Differentially expressed genes and isoforms associated with HGs were analysed using linear models.ResultsThe classification of grade 1 and grade 3 tumours based on RNA-sequencing data achieved high accuracy (area under the receiver operating characteristic curve = 0.97). The association between recurrence-free survival rate and HGs was confirmed in the study population (hazard ratio of grade 3 versus 1 was 2.62 with 95 % confidence interval = 1.04-6.61). The TG model enabled us to reclassify grade 2 tumours as high TG and low TG gene or isoform grade. The risk of recurrence in the high TG group of grade 2 tumours was higher than in low TG group (hazard ratio = 2.43, 95 % confidence interval = 1.13-5.20). We found 8200 genes and 13,809 isoforms that were differentially expressed between HG1 and HG3 breast cancer tumours.ConclusionsGene- and isoform-level expression data from RNA-sequencing could be utilised to differentiate HG1 and HG3 tumours with high accuracy. We identified a large number of novel genes and isoforms associated with HG. Grade 2 tumours could be reclassified as high and low TG, which has the potential to reduce over- and under-treatment if implemented clinically.

Dataset Information

Invasive breast cancer: stratification of histological grade by gene-based assays: a still relevant example from an older data set.

Aims

Methods and results

Conclusion

Publications

Invasive breast cancer: stratification of histological grade by gene-based assays: a still relevant example from an older data set.

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