Introduction to BREACH
Principal Investigator: Dr Gloria Petralia
Welcome to the BREACH website, where you can access details on the study objectives, design, and population.
Core Team:
Clinical Trials Unit
Thrombosis Research Institute
Emmanuel Kaye Building
1b Manresa Road
Chelsea, London
SW3 6LR
United Kingdom
E-mail: breach@tri-london.ac.uk
About BREACH
BREACH is a prospective study of patients with newly diagnosed breast cancer scheduled to receive standard chemotherapy.
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Overview
Overview
The correlation between tumour biology and the coagulation cascade is being investigated with increasingly marked interest. The BREACH study was designed to assess the clotting profile and proteomic characteristics in breast cancer patients pre, post and during treatment in order to provide better insight in the biology of cancer. This pilot study will pave the way to large trials to explore a correlation between important clinical indicators such as survival and response to therapy.
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Clinical Need
Clinical Need
Venous thromboembolism (VTE) is a relatively common and serious event in individuals with malignancy. Its occurrence complicates the clinical care of the patient and can have a profoundly negative impact on an already compromised quality of life.
Unfortunately, both the prevention and treatment of blood clots increase the risk of bleeding. Better understanding of blood clot risk and treatment in patients with cancer undergoing chemotherapy will help to improve prevention and quality of life in these patients.
Cancer patients receiving chemotherapy do not routinely receive antithrombotic prophylaxis unless they have a history of VTE. This is probably because there is a perception that the risk is low and prophylactic methods are logistically complicated. It may be possible however to identify a group of cancer patients at very high risk of VTE (risk stratification) for whom oncologists would agree that prophylaxis is warranted.
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Status
Status
Recruitment has now been closed and data collection has now been completed. All samples have been analysed. Data is being transferred to the study statistician for statistical analysis.
Study Details
BREACH is a prospective, single centre study of patients with newly diagnosed breast cancer, designed to apply basic science which will help to enhance human health and well-being by improving management and treatment in breast cancer patients.
Findings from BREACH will help to improve management and treatment in these patients.
The study was conducted at the Barts and the London NHS Trust.
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Rationale
Rationale
Venous thromboembolism (VTE, blood clots in the blood vessels) is estimated to be the second most common cause of death in cancer patients, with up to 60% of those deaths occurring at an otherwise favourable time in the history of the cancer. Cancer patients are also known to be more susceptible to bleeding complications either due to the cancer itself or its treatment.
In one study, it was estimated that one in seven cancer patients will die of potentially avoidable pulmonary embolism (PE) rather than cancer itself. There is good evidence that post-operative thromboprophylaxis is effective and safe in cancer patients undergoing surgery.
Many cancer patients are admitted to hospital to deal with acute medical complications, e.g. hypercalcaemia, febrile neutropenia, pain crises. It is unclear whether such patients routinely receive thromboprophylaxis. Furthermore, it is unknown whether cancer patients admitted for end-of-life care receive thromboprophylaxis.
The results of the CLOT trial have shown the superiority of long-term low molecular weight heparin (LMWH) over warfarin in cancer patients with acute VTE. Interestingly, a subgroup analysis showed a better survival in patients receiving 6 months thromboprophylaxis with LMWH when compared to warfarin. The FAMOUS Study showed an increase in median survival in patients with advanced malignancy receiving LMWH compared to placebo. A study on patients with small cell lung cancer showed a significant survival advantage in patients receiving LMWH in combination with their chemotherapy. Finally, the MALT study showed a marked survival advantage in patients with solid tumours receiving LMWH when compared to placebo.
We recognised the need for a study to provide data on the biomarkers of coagulation in cancer patients and the relationship with VTE.
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Objectives & End Points
Objectives & End Points
Primary Objective
- To assess the coagulation, proteomics and micro-particles profile in patients with newly diagnosed malignancy of the breast
Secondary Objectives
- To assess the natural fluctuations of selected biomarkers of coagulation including:
- Activated Prothrombin time (APTT)
- Prothrombin time (PT)
- Microparticles activity (MP)
- sP-Selectin (sPS)
- Tissue Factor activity (TF)
- D-Dimer (DD)
- Prothrombin F1F2
- Microparticle-Tissue Factor (MP-TF)
- To assess the overall profile in platelet micro-particles array
- To assess the proteomic assays of serum proteases contemplated as inflammatory mediators
End Points
- Variations in coagulation biomarkers, platelet micro-particles arrays and serum proteases profile according to treatment
- Variations in the measured biomarkers profile according to stage; response to treatment and outcome
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Study Design
Study Design
BREACH is a prospective study of subjects with newly diagnosed breast cancer fulfilling the inclusion/exclusion criteria. Patients were treated according to local best practice, and this study, or ‘both the exclusion and inclusion’ did not entail any experimental intervention. Blood samples were collected from the patients according to the protocol with no additional procedures required by the study. Samples collected at the baseline, chemotherapy and post-treatment stages were used to assess the coagulation profile, proteomics assays and platelet micro-particles.
The progression after diagnosis and changes since baseline have been monitored for:
- Acute venous thromboembolism
- Bleeding complications
- Central venous catheter
- Chemotherapy
- Death
- Hormonal therapy
- Peripheral arterial thrombosis
- Post-operative staging
- Radiotherapy
- Surgical treatment
- Suspicion of venous thromboembolism
- Venous thromboembolism prophylaxis
- Vascular incidents
Study Population
All patients with a newly histological diagnosis of breast cancer stage 2 or higher expected to receive treatment with chemotherapy were considered for enrolment. For this pilot study the sample size of 100 has been determined by practical considerations.
Each recruited patient had to meet the study criteria and had to have given consent.
Inclusion Criteria
An answer of “no” to any of the following excludes the subject from entering the study.
- Patients with newly histological diagnosis of Breast Cancer Stage II or higher expected to receive treatment with Chemotherapy.
- Female
- Age over 18 years
- Signed Informed Consent
Exclusion Criteria
An answer of “yes” to any of the following excludes the subject from entering the study.
- Severe anaemia (documented haemoglobin < 6.5 gr/dl)
- No further follow-up envisaged in the enrolment centre.
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Data Collection
Data Collection
Blood samples were collected from the patients according to the protocol with no additional procedures required by the study. Selected data were collected from the patients’ clinical records according to the specification in the case report form (CRF). Patient progress was monitored for up to 2 years, with special attention to medical history, thromboembolic risk factors, treatment and outcome. Blood samples were used to assess the coagulation profile, proteomics assays and platelet micro-particles.
Flow Chart
