Praegnant Breast Cancer: Early/Advanced/Metastatic

Study Overview
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Brief Summary
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Among patients with breast cancer the subgroup of patients with metastases are considered the group of patients with the worst prognosis. Not only regard-ing therapy decisions but also with regard to quality assured healthcare and health economics this entity of patients remains a challenge. Recently, novel advances in breast cancer therapy aim at the targeted therapy of tumor entities and identification of patients, for whom the greatest therapy benefit, and the least side effects are expected. However molecular assessment of the patient and the tumor in the metastatic situation is not performed on a routine basis and in many cases tumor character-istics from the primary tumor are considered reliable enough to make therapy decisions for the metastatic patients. Although molecular reassessment of tu-mor characteristics from tumor material of the metastasis is recommended in national guidelines, only a minority of patients is biopsied, because of the inva-siveness of the procedure, even though biopsy related complications are reported to be rare. With modern analytic methods from blood based biomaterial there seems to be an opportunity to correlate blood based tumor assessments with actual charac-teristics of the tumor. These include expression analysis, tumor mutation analy-sis, tumor gene copy number aberrations and others. One of the main aims of the PRAEGNANT study is therefore to establish an infrastructure for the compre-hensive analysis of tumor and metastatic molecular characteristics of the patient and the tumor. Furthermore, health care related outcomes as well as health economics provide novel approaches for integration of patients in study conduct and health care awareness and are study aims of the PRAEGNANT study.

Official Title
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Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Adjuvant and Advanced/Metastatic Setting: Health Care Research, Pharmacogenomics, Biomarkers, Health Economics

Conditions
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Advanced/Metastatic Breast Cancer, Breast Cancer (Early Breast Cancer)

Intervention / Treatment
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* Procedure: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the early breast cancer setting: Adult breast cancer patients (age ≥18 years) Patients with breast cancer and no evidence of distant metastases with a diagnosis not longer than 91 days before study entry Patients, who are able and willing to sign the informed consent form Inclusion Criteria for the advanced/metastatic setting: Adult women aged ≥18 years Patients with the diagnosis of invasive breast cancer (in German: Mammakarzinom, as op-posed to non-invasive= ductales Carcinoma in situ; irrespective of status of BC, e.g. TNM, re-ceptor status etc.) and Patients, who are willing and able to sign the informed consent form Patients with metastatic or locally advanced, inoperable disease proven by clinical measures (i.e. standard imaging) Exclusion Criteria: Patients who did not sign the informed consent form Patients, who are not eligible for observation due to non-availability and/or severe comor-bidities as evaluated by the treating physician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Advanced/metastatic breast cancer<br>3,500 patients with locally advanced, inoperable/metastatic breast cancer in any line of treatment (e.g. 1st, 2nd, 3rd, or ≥ 4th line). | Procedure: Blood sampling<br>* A blood sample will be taken during a routine blood draw<br>|
| Early breast cancer<br>10,000 patients with breast cancer in the neoadjuvant and adjuvant (early breast cancer) setting independent of treatment regimen. | Procedure: Blood sampling<br>* A blood sample will be taken during a routine blood draw<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MBC (Metastatic Breast Cancer): Discovery of biomarkers, which predict progression free survival (PFS) | Analyses will be done separately for each therapy line. Biomarkers include gene expression profiling of the primary tumor and the corresponding metastases, somatic mutations, germline genetic variation, epigenetic changes and miRNA variation up to a total of 500,000 biomarkers. | PFS defined as the time to the first progression after study inclusion from the last time of progression before or at study entry | 
| EBC (Early Breast Cancer): Assessment of disease free sur-vival (DFS) | DFS defined as the time to the first disease recurrence after study inclusion from time of primary diagnosis before or at study entry | up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MBC: Assessment of overall survival (OS) | OS is defined as the time to death from the date of the last progression before or at study entry. | OS is defined as the time to death from the date of the last progression before or at study entry. | 
| MBC: Assessment of breast cancer specific survival (BCSS) | BCSS is defined as the time to to death due to breast cancer from the date of the last progression before or at study entry. | Time to death from the date of the last progression before or at study entry. | 
| MBC: Objective response | Objective response is defined as the best-documented response to the therapy started at study entry or the last therapy started before study entry. | up to 60 months | 
| MBC: Description of therapies used in the metastatic setting | Therapies will be categorized and descriptive statistics will be presented. | after 60 months (after study completion) | 
| MBC: Quality of life | Assessed with EORTC QlQ-C30 and Visual Analog Scala | Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| MBC: Therapy adherence | Defined as the percentage of patients in which treat-ments which are terminated as per patients' wish or because of treatment related side effect. | up to 60 months | 
| MBC: Influencing Factors of Depression in patients with metastatic breast cancer | Depression will be assessed by patient reported questionnaires e.g. CESD-R. | Study entry and every 3 month or following a change of a therapy line (event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| MBC: Incidence of adverse events, serious adverse events will be reported. | According to NCI Common Toxicity Criteria Version 4.03. | up to 60 months | 
| MBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial. | Number of patients who will receive molecular testing results compared to the total number of included patients. | Once at end of study | 
| MBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations) | Assessed with a physician and patient questionnaire and documentation of possible confirmatory testing for changes in therapy or eligibility for interventional clinical trial screening. | Once at end of study | 
| MBC: Health economics for women with metastatic and/or locally advanced, inoperable breast cancer. | EORTC QLQ C-30 (Version 3.0) (among others) and actu-al documented costs of diagnostic procedures, therapies, treatment of side effects and care for tumor-associated symptoms will be used to calculate health care costs, quality adjusted life years (QALY) and incremental cost effectiveness ratios (ICER) between patient groups. | Study entry and every 3 month or following a change of a therapy line (event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| MBC: Patient reported influencing factors on therapy adherence in patients metastatic and/or locally advanced, inoperable breast cancer. | Patient reported adherence for orally administered therapies will be assessed with suitable questionnaires. | Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| EBC: Assessment of distant disease-free survival (DDFS) | DDFS defined as the time to the first distant disease recurrence after study inclusion from time of primary diagnosis before or at study entry. | Up to 60 months | 
| EBC: Quality of life | Assessed with EORTC QLQ C-30 (Version 3.0), EORTC QLQ-BR23 and the EQ-Visual Analog Scale (VAS) | Study entry and every 3 month or following a change of a therapy line (event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| EBC: Assessment of overall survival (OS) | OS is defined as the time to death from the date of the primary diagnosis before or at study entry. | OS is defined as the time to death from the date of the last progression before or at study entry. | 
| EBC: Assessment of breast cancer specific survival (BCSS) | BCSS is defined as the time to death due to breast cancer from the date of the primary diagnosis before or at study entry. | Time to death due to breast cancer from the date of the primary diagnosis before or at study entry. | 
| EBC: Description of therapies used in the early breast cancer setting | Therapies will be categorized, and descriptive statistics will be presented. | after 60 months (after study completion) | 
| EBC: Percentage of women, who will receive results of molecular tests undertaken in the context of the scientific objectives of this trial. | Number of patients who will receive molecular testing results compared to the total number of included pa-tients. | Once at end of study | 
| EBC: Feasibility and satisfaction regarding receipt of molecular testing results (including hereditary genetic alterations) | Assessed with a physician and patient questionnaire and documentation of possible confirmatory testing for changes in therapy or eligibility for interventional clinical trial screening. | Once at end of study | 
| EBC: Therapy adherence | Defined as the percentage of patients in which treat-ments which are terminated as per patients' wish or because of treatment related side effect | up to 60 months | 
| EBC: Health economics for women with breast cancer | EORTC QLQ C-30 (Version 3.0) (among others) and actu-al documented costs of diagnostic procedures, thera-pies, treatment of side effects and care for tumor-associated symptoms will be used to calculate health care costs, quality adjusted life years (QALY) and incre-mental cost effectiveness ratios (ICER) between patient groups. | up to 60 months | 
| EBC: Influencing Factors of Depression in patients with breast cancer | Depression will be assessed by patient reported ques-tionnaires e.g. CESD-R. | Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| EBC: Patient reported influencing factors on therapy adherence in patients with early breast cancer. | Patient reported adherence for orally administered therapies will be assessed with suitable questionnaires. | Study entry and every 3 month or following a change of a therapy line(event-associated, e.g. after progression) until Month 24. Every 6 months from Month 24 until Death or withdrawal of consent | 
| EBC: Incidence of adverse events, serious ad-verse events will be reported. | NCI Common Toxicity Criteria Version 4.03. | up to 60 months |