Dataset Information

Pattern of distant metastases in inflammatory breast cancer - A large-cohort retrospective study.

ABSTRACT: Inflammatory breast cancer (IBC) is a fatal form of breast cancer. IBC patients present with unfavorable prognosis mainly attributable to high risk of distant metastasis. Thus, in this cohort study, we aimed to explore metastatic profiles of different molecular subtypes of IBC and elucidate the clinical and prognostic characteristics among different metastatic sites. Patients diagnosed as IBC between 2010 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Chi-square tests were performed to compare metastatic distribution among different molecular subtypes. We further used odds ratio calculation to analyze the combined metastatic patterns. Kaplan-Meier methods and multivariate Cox regression models were applied to analyze survival data among different metastatic organs. In total, we enrolled 635 IBC patients between 2010 and 2014 as the training cohort and 242 IBC patients between 2015 and 2016 as the validation cohort, All the included patients were recorded with known metastatic status, follow-up data and molecular subtype. In the present study, we elaborated the following three points: (1) Elucidating the distribution of single-organ metastases in IBC. Bone and brain were the most and least common metastatic lesions for all subtypes of IBC, separately. (2) Clarifying the combined metastatic patterns and tendency of co-metastases. Bi-organ metastasis occurred most frequently among all combined metastases. Several combinations, such as liver and bone, lung and brain, were preferential for bi-organ metastasis. (3) Analyzing prognostic values of single-organ and bi-organ metastases. All single-organ distal metastases were independent risk factors indicating an unfavorable prognosis. In conclusion, our results would provide more information for clinical decision and future studies.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6930435 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pattern of distant metastases in inflammatory breast cancer - A large-cohort retrospective study.

Wang Zheng Z Chen Mo M Pan Junjie J Wang Xuan X Chen Xiao-Song XS Shen Kun-Wei KW

Journal of Cancer 20200101 2

Inflammatory breast cancer (IBC) is a fatal form of breast cancer. IBC patients present with unfavorable prognosis mainly attributable to high risk of distant metastasis. Thus, in this cohort study, we aimed to explore metastatic profiles of different molecular subtypes of IBC and elucidate the clinical and prognostic characteristics among different metastatic sites. Patients diagnosed as IBC between 2010 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) databas ...[more]

PMID: 31897225

Similar Datasets

Project description:Background and aimsBreast cancer-related death is attributable mainly to metastasis. Inflammatory breast cancer (IBC) is an infrequent subtype of breast cancer that shows a relatively high rate of metastasis. In this study, we aimed to compare the metastatic patterns and prognostic outcomes of IBC and non-inflammatory breast cancer (non-IBC).MethodsWe extracted data between 2010 and 2014 from the Surveillance, Epidemiology and End Results (SEER) database. The Chi-square test and Fisher's exact test were used to compare the categorical parameters among different groups. Logistic regression was applied for multivariate analysis. The Kaplan-Meier method and multivariate Cox regression models were performed to analyze prognosis.ResultsWe enrolled 233,686 breast cancer patients between 2010 and 2014 in our research, including 2806 IBC and 230,880 non-IBC patients. Compared with the non-IBC group, the IBC group tended to have a higher incidence of the human epidermal growth factor receptor 2 positive (HER2+) and triple-negative breast cancer (TNBC) subtypes, older age, a higher rate of unmarried status, a lower incidence of black race, poorer tumor differentiation, larger tumor sizes, and a higher frequency of regional lymph node invasion. IBC and non-IBC shared similar trends in molecular subtypes among different metastatic organs. The percentage of the hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) subtype decreased gradually in patients with lung (IBC 42.5%, non-IBC 55.7%), distant lymph node (IBC 41.5%, non-IBC 54.6%), liver (IBC 31.1%, non-IBC 46.7%), and brain (IBC 30.6%, non-IBC 47.9%) metastases compared with that in patients with bone (IBC 50.8%, non-IBC 69.0%) metastasis in both cohorts. In both the IBC and non-IBC cases, the proportion of visceral metastases increased in the TNBC subtype, especially brain metastasis (IBC 26.4%, non-IBC 21.2%), which had the largest increase. The frequencies of all sites (bone, lung, liver, brain, and distant lymph node) in IBC were much higher than those in non-IBC (bone: IBC 21.1%, non-IBC 3.0%; lung: IBC 11.4%, non-IBC 1.4%; liver: IBC 9.6%, non-IBC 1.2%; brain: IBC 2.6%, non-IBC 0.3%; distant lymph node: IBC 12.9%, non-IBC 1.0%). The most frequent bi-site metastasis was the bone and liver (IBC 2.5%, non-IBC 0.3%), and the most frequent tri-site combination was the bone, lung, and liver (IBC 1.1%, non-IBC 0.2%). Kaplan-Meier curves and multivariate Cox regression models suggested that the IBC cohort had poorer overall survival [hazard ratio (HR) 1.602, 95% confidence interval (CI) 1.496-1.716, p?<?0.001] and breast cancer-specific survival (HR 1.511, 95% CI 1.402-1.628, p?<?0.001) than the non-IBC cohort. Furthermore, univariate and multivariate analyses indicated that IBC was an independent prognostic factor in patients with different metastatic sites.ConclusionIBC and non-IBC patients presented with different metastatic frequencies, clinical features and prognostic outcomes. Our findings provide more information for therapeutic decision making and clinical study designs.

Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development. Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

Project description:BACKGROUND:The development of metastases involves the dissociation of cells from the primary tumor to penetrate the basement membrane, invade and then exit the vasculature to seed, and colonize distant tissues. The last step, establishment of macroscopic tumors at distant sites, is the least well understood. Four isogenic mouse breast cancer cell lines (67NR, 168FARN, 4TO7, and 4T1) that differ in their ability to metastasize when implanted into the mammary fat pad are used to model the steps of metastasis. Only 4T1 forms macroscopic lung and liver metastases. Because some miRNAs are dysregulated in cancer and affect cellular transformation, tumor formation, and metastasis, we examined whether changes in miRNA expression might explain the differences in metastasis of these cells. METHODOLOGY/PRINCIPAL FINDINGS:miRNA expression was analyzed by miRNA microarray and quantitative RT-PCR in isogenic mouse breast cancer cells with distinct metastatic capabilities. 4T1 cells that form macroscopic metastases had elevated expression of miR-200 family miRNAs compared to related cells that invade distant tissues, but are unable to colonize. Moreover, over-expressing miR-200 in 4TO7 cells enabled them to metastasize to lung and liver. These findings are surprising since the miR-200 family was previously shown to promote epithelial characteristics by inhibiting the transcriptional repressor Zeb2 and thereby enhancing E-cadherin expression. We confirmed these findings in these cells. The most metastatic 4T1 cells acquired epithelial properties (high expression of E-cadherin and cytokeratin-18) compared to the less metastatic cells. CONCLUSIONS/SIGNIFICANCE:Expression of miR-200, which promotes a mesenchymal to epithelial cell transition (MET) by inhibiting Zeb2 expression, unexpectedly enhances macroscopic metastases in mouse breast cancer cell lines. These results suggest that for some tumors, tumor colonization at metastatic sites might be enhanced by MET. Therefore the epithelial nature of a tumor does not predict metastatic outcome.

Dataset Information

Pattern of distant metastases in inflammatory breast cancer - A large-cohort retrospective study.

Publications

Pattern of distant metastases in inflammatory breast cancer - A large-cohort retrospective study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure