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Diversity index as a novel prognostic factor in breast cancer.

ABSTRACT: Intratumoral genetic heterogeneity leads to tumor progression and therapeutic resistance. However, due to the difficulty associated with its assessment, the use of this heterogeneity as a prognostic or predictive marker remains limited. To investigate the significance of the Shannon diversity index of gene copy number variation as a tool for measuring genetic heterogeneity in breast cancer, we performed fluorescence in situ hybridization of c-MYC in two sets of invasive breast cancer samples and correlated the Shannon index of c-MYC copy number variation with clinicopathologic features and patient survival. The Shannon index was correlated with average c-MYC copy number and was higher in tumors in which c-MYC was amplified and in those with c-MYC genetic or regional heterogeneity. A high Shannon index was associated with adverse pathologic features including high histologic grade, lymphovascular invasion, p53 overexpression, high Ki-67 proliferation index and negative hormone receptor status. It was also associated with poor disease-free survival in the whole group, in a subgroup excluding c-MYC-amplified cases, and in the hormone receptor-positive subgroup of both a test and a validation set. A high Shannon index for FGFR1 gene copy number variation was also an independent adverse prognostic factor. Our findings suggest that the Shannon diversity index is a measure of intratumoral heterogeneity and can be used as a prognostic factor in breast cancer.

SUBMITTER: Chung YR

PROVIDER: S-EPMC5722549 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Diversity index as a novel prognostic factor in breast cancer.

Chung Yul Ri YR Kim Hyun Jeong HJ Kim Young A YA Chang Mee Soo MS Hwang Ki-Tae KT Park So Yeon SY

Oncotarget 20170928 57

Intratumoral genetic heterogeneity leads to tumor progression and therapeutic resistance. However, due to the difficulty associated with its assessment, the use of this heterogeneity as a prognostic or predictive marker remains limited. To investigate the significance of the Shannon diversity index of gene copy number variation as a tool for measuring genetic heterogeneity in breast cancer, we performed fluorescence in situ hybridization of <i>c-MYC</i> in two sets of invasive breast cancer samp ...[more]

PMID: 29228597

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Project description:ObjectiveThis study aims at investigating the potential prognostic significance of the breast immune prognostic index (BIPI) in breast cancer patients who received neoadjuvant chemotherapy (NACT).MethodsThe optimal cutoff value was calculated through the receiver operating characteristic curve (ROC). The correlations between BIPI and clinicopathologic characteristics were determined by the chi-square test or Fisher's exact test. The Kaplan-Meier method was used to estimate the survival probability, and the log-rank test was used to analyze the differences in the survival probability among patients. The univariate and multivariate Cox proportional hazard regression model was used to screen the independent prognostic factors. A prognostic nomogram for disease-free survival (DFS) and overall survival (OS) was built on the basis of the multivariate analyses. Furthermore, the calibration curve and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.ResultsAll enrolled patients were split into three subgroups based on the BIPI score. The mean DFS and OS of the BIPI score 0 group and BIPI score 1 group were significantly longer than those of the BIPI score 2 group (42.02 vs. 38.61 vs. 26.01 months, 77.61 vs. 71.83 vs. 53.15 months; p < 0.05). Univariate and multivariate analyses indicated that BIPI was an independent prognostic factor for patients' DFS and OS (DFS, hazard ratio (HR): 6.720, 95% confidence interval (CI): 1.629-27.717; OS, HR: 8.006, 95% CI: 1.638-39.119). A nomogram with a C-index of 0.873 (95% CI: 0.779-0.966) and 0.801 (95% CI: 0.702-0.901) had a favorable performance for predicting DFS and OS survival rates for clinical use by combining immune scores with other clinical features. The calibration curves at 1-, 3-, and 5-year survival suggested a good consistency between the predicted and actual DFS and OS probability. The DCA demonstrated that the constructed nomogram had better clinical predictive usefulness than only BIPI in predictive clinical applications of 5-year DFS and OS prognostic assessments.ConclusionsThe patients with low BIPI score have better prognoses and longer DFS and OS. Furthermore, the BIPI-based nomogram may serve as a convenient prognostic tool for breast cancer and help in clinical decision-making.

Project description:BACKGROUND: A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication. METHODS: The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer. RESULTS: We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are equally important to stratify different survival outcomes in non-TNBC as in TNBC. We also showed that the NPI retains the ability to stratify and predict survival of TNBC patients. CONCLUSION: The importance of this study relies on the need of prognostication improvements on TNBC, showing, at a clinical standpoint, that Nottingham Prognostic Index is as a truthful prognostic tool in TNBC.

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Diversity index as a novel prognostic factor in breast cancer.

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Diversity index as a novel prognostic factor in breast cancer.

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