Observational study of coagulation activation in early breast cancer: development of a prognostic model based on data from the real world setting

Abstract

BackgroundCancer and coagulation activation are tightly related. The extent to which factors related to both these pathologic conditions concur to patient prognosis intensely animates the inherent research areas. The study herein presented aimed to the development of a tool for the assessment and stratification of risk of death and disease recurrence in early breast cancer.MethodsBetween 2008 and 2010, two hundreds thirty-five (N: 235) patients diagnosed with stage I–IIA breast cancer were included. Data on patient demographics and clinic-pathologic features were collected in course of face-to-face interviews or actively retrieved from clinical charts. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), fragment 1 + 2 (F1 + 2), thrombin antithrombin complex (TAT), factor VIII (FVIII), and D-dimer (DD) were measured at breast cancer diagnosis and prior to any therapeutic procedure, including breast surgery. The risk of death was computed in terms of overall survival (OS), which was the primary outcome. For a subset of patients (N = 62), disease free survival (DFS) was also assessed as a measure of risk of disease recurrence.ResultsMedian follow up was 95 months (range 6–112 months). Mean age at diagnosis was 60.3 ± 13.4 years. Cancer cases were more commonly intraductal carcinomas (N: 204; 86.8%), pT1 (131; 55.7%), pN0 (141; 60%) and G2 (126; 53.6%). Elevated levels of PAI-1 (113; 48.1%) represented the most frequent coagulation abnormality, followed by higher levels of F1 + 2 (97; 41.3%), DD (63; 27.0%), TAT (34; 40%), and FVIII (29; 12.3%). In univariate models of OS, age, pT, DD, FVIII were prognostically relevant. In multivariate models of OS, age (p = 0.043), pT (p = 0.001), levels of DD (p = 0.029) and FVIII (p = 0.087) were confirmed. In the smaller subgroup of 62 patients, lymph node involvement, percent expression of estrogen receptors and levels of FVIII impacted DFS significantly.ConclusionsWe developed a risk assessment tool for OS including patient- and cancer-related features along with biomarkers of coagulation activation in a cohort of early BC patients. Further studies are warranted to validate our prognostic model in the early setting and eventually extend its application to risk evaluation in the advanced setting for breast and other cancers.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1511-x) contains supplementary material, which is available to authorized users.

Procoagulant Disorders in Patients with Newly Diagnosed Pancreatic Adenocarcinoma

“…However, we demonstrated that elevated TAT levels were present not only in metastatic PA patients but in majority of patients with pancreatic cancer at the time of diagnosis. The findings reported here are in agreement with recently published study of Mandoj et al, which found increased TAT plasma levels in 34.4% of women with early breast cancer, before any anticancer therapy [ 27 ].…”

Observational Multicenter Study on the Prognostic Relevance of Coagulation Activation in Risk Assessment and Stratification in Locally Advanced Breast Cancer. Outline of the ARIAS Trial

“…This trial is well placed within a research pipeline on coagulation and cancer. It is primarily aimed at validating the prognostic accuracy of our previously developed prognostic model in an independent cohort of breast cancer patients [9]. The ARIAS trial has received formal approval by the IRB of the coordinating center.…”

“…In our prior study, we identified patient-and disease-related characteristics with prognostic relevance and included them into a prognostic model which proved accuracy in risk assessment and stratification in reference to the survival outcomes assessed in a cohort of 235 breast cancer patients diagnosed and treated at the IRCCS Regina Elena National Cancer Institute (IRE) between 2008 and 2010 [9]. Age, pathologic T (pT), baseline circulating levels of D-dimer (DD) and factor VIII (FVIII) proved prognostically relevant in multivariate models of overall survival (OS).…”

“…Indeed, the ARIAS was conceived with validation purposes in reference to our primary endpoint, i.e., pCR. Conversely, no VTE-related endpoints have been addressed in our prior study [9]. Thus, data from the ARIAS will be used to identify prognostically relevant factors in reference to VTE outcomes.…”

“…Based on procedures whose details will be summarized in the methods section, we developed a prognostic model for the assessment and stratification of risk of death upon factors related to relevant clinic-pathologic characteristics and coagulation profile. This tool is shown in Table 1 and has proven efficacy in distinguishing patients' categories characterized by significantly different survival estimates [9]. On this basis, more recently, we have required and obtained formal approvals from the dedicated institutional bodies for the conduct of a validation study on an independent cohort of breast cancer patients consenting to participate and to be prospectively followed in a trial on the prognostic relevance of biomarkers of coagulation activation for risk assessment and stratification in reference to patients' important outcomes in breast cancer.…”