Reaching for Evidence-baSed Chemotherapy Use in Endocrine Sensitive Breast Cancer

Study Overview
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Brief Summary
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Systematic assessment of survival data of patients who have been tested with EndoPredict®; prospective proof that patients with low risk classification by EndoPredict® (EPclin) can safely forgo chemotherapy and be treated with endocrine therapy alone.

Detailed Description
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The goal of the study is to receive current and comprehensive information about the diseasefree (remote metastasis free and recurrence free) interval of EndoPredict® low risk patients. The study is organized and managed by the NOGGO e.V. (North Eastern German Society of Gynaecological Oncology e.V.) study coordination office under the existing and efficient infrastructure. All patients who receive gene expression analysis with EndoPredict® and satisfy the remaining inclusion / exclusion criteria may participate in the study. Data collection is prospective and non-interventional. The recruitment of the required patients is expected to take a maximum of 36 months . It must be emphasized that the study is data collection only and not an interventional study. This means that the choice and implementation of the therapy as well as the treatment assessments and frequency during and after the treatment can only be determined by the Investigator. The decision to participate in the study is independent of the patient´s therapy within the framework of a study. Patient data will be recorded at the time of inclusion and once a year thereafter. Patient follow-up will be by phone from the second year onward. Primary objective is to show that female patients who have been tested as low risk by EPclin and have been treated with endocrine therapy only for at least 5 years have a 10-year DMFS rate > 90% (lower boundary of the one-sided 95% confidence interval). Secondary objectives comprise the evaluation of DMFS (distant metastasis free survival) , DFS (disease free survival) and OS (overall survival) rates at different time points and for different groups. Assessment of the given chemotherapy regimens and the given endocrine therapy will be performed and the proportions of patients will be determined with respect to the received treatment and its duration in different groups. Furthermore, the proportion of patients in whom the tumor board recommendation follows the EndoPredict® result and the proportion of patients actually treated according to EndoPredict® result will be determined. The association between outcome and treatment, EPclin, EP, and classical prognostic factors will be investigated in different groups of patients. The correlation and concordance between EPclin calculations derived from biopsies and surgical specimens will be assessed.

Official Title
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Prospective Assessment of Disease Progression in Primary Breast Cancer Patients Undergoing EndoPredict® Gene Expression Testing - a Care Research Study

Conditions
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Primary Invasive Breast Cancer, Estrogen Receptor Positive Tumor, Human Epidermal Growth Factor Receptor 2 Negative Tumor

Intervention / Treatment
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* Other: Observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Tested with EndoPredict within the previous 6 months before inclusion Age ≥ 18 years Patients with primary invasive breast cancer, Stage I/II ER-positive HER2-negative N0 or N1 (1-3 positive lymph nodes) T1 - T3 Exclusion Criteria: Inflammatory breast cancer Bilateral breast cancer Breast cancer in the last 10 years Other invasive malignancies in the last 5 years

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Observational Group<br>Patients with primary invasive breast cancer, Stage I/II; ER positive, HER2 (human epidermal growth factor receptor 2) negative, N0-N1, T1-T3, tested with EndoPredict®, age over 18 years, informed consent | Other: Observation<br>* Visit 1 Informed consent Medical history Demographics Result of EndoPredict® Test Status of menopause Disease status Tumor board decision Planned anti-tumor-therapy Visit 2, 1 year after inclusion This visit will be documented at the study site Status of menopause Disease status Anti-tumor therapy Survival Following visits For these visits, patients will be asked directly through the Center for Clinical Trials of the Philipps-University Marburg (KKS Marburg) via phone. Status of Menopause Disease status Anti-tumor therapy Survival Treatment after end of the study The patient will be treated during and after end of study by physician's choice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant metastasis free survival | To show that female patients who have been tested as low risk by EndoPredict® (EPclin) and have been treated with endocrine therapy only for at least 5 years have a 10-year distant metastasis-free survival (DMFS) > 90 % (lower boundary of the one-sided 95 % confidence interval) | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DMFS low risk | Assessment of DMFS of patients with EPclin low risk (or EP low risk [EP score <5] if EPclin cannot be calculated after surgery in the neoadjuvant setting) (in all patients, in the relevant target group and separately in men and women and in pre- and postmenopausal women with regard to treatment). | 3, 5 and 10 years | 
| DFS low risk | Assessment of DFS of patients with EPclin low risk (or EP low risk [EP score <5] if EPclin cannot be calculated after surgery in the neoadjuvant setting) (in all patients, in the relevant target group and separately in men and women and in pre- and postmenopausal women with regard to treatment). | 3, 5 and 10 years | 
| OS low risk | Assessment of OS of patients with EPclin low risk (or EP low risk [EP score <5] if EPclin cannot be calculated after surgery in the neoadjuvant setting) (in all patients, in the relevant target group and separately in men and women and in pre- and postmenopausal women with regard to treatment). | 3, 5 and 10 years | 
| DMFS high risk | Assessment of DMFS of patients with EPclin high risk in all patients and separated in men and women as well as pre- and postmenopausal women with regard to treatment). | 3, 5 and 10 years | 
| DFS high risk | Assessment of DFS of patients with EPclin high risk in all patients and separated in men and women as well as pre- and postmenopausal women with regard to treatment). | 3, 5 and 10 years | 
| OS high risk | Assessment of OS of patients with EPclin high risk in all patients and separated in men and women as well as pre- and postmenopausal women with regard to treatment). | 3, 5 and 10 years | 
| DMFS high risk + low risk | DMFS for patients who have / have not been treated according to EPclin/ EP result (all patients and subgroup analyses as specified in secondary objectives 1 and 2). | 3, 5 and 10 years | 
| DFS high risk + low risk | DFS for patients who have / have not been treated according to EPclin/ EP result (all patients and subgroup analyses as specified in secondary objectives 1 and 2). | 3, 5 and 10 years | 
| OS high risk + low risk | OS for patients who have / have not been treated according to EPclin/ EP result (all patients and subgroup analyses as specified in secondary objectives 1 and 2). | 3, 5 and 10 years | 
| Portion of patients tumor board follows the EndoPredict® result | Assessment of the proportion of patients in whom the tumor board follows the EndoPredict® result in regard to treatment recommendation (in all patients and separately for men and women). | 1 year | 
| Portion of patient treated according EndoPredict® result | Assessment of the proportion of patients who were actually treated according to the EndoPredict® result (in all patients and separately for men and women). | 1 year | 
| Prognostic Performance of classical prognostic factors compared to EndoPredict® | Assessment of the classical prognostic factors tumor size, nodal status, grading, quantitative estrogen receptor, quantitative progesterone receptor and quantitative Ki67 and evaluation of their prognostic performance compared to EPclin and EP in univariate and multivariate analyses of DMFS, DFS, OS (in all patients, separately for men and women, only in patients who have been treated according to the EndoPredict® result). | 3, 5 and 10 years | 
| DMFS low risk vs. high risk | Assessment of DMFS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC (immunohistochemistry)-classification. | 3, 5 and 10 years | 
| DFS low risk vs. high risk | Assessment of DFS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification. | 3, 5 and 10 years | 
| OS low risk vs. high risk | Assessment of OS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification. | 3, 5 and 10 years | 
| DMFS of patient proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors | Assessment of proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors, respectively, and stratified analysis of DMFS of patients with ki67-values low (≤ 10%)/ intermediate (11-24%)/ high (≥ 25%) and EPclin low risk vs high risk. | 3, 5 and 10 years | 
| DFS of patient proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors | Assessment of proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors, respectively, and stratified analysis of DFS of patients with ki67-values low (≤ 10%)/ intermediate (11-24%)/ high (≥ 25%) and EPclin low risk vs high risk. | 3, 5 and 10 years | 
| OS of patient proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors | Assessment of proportion of EPclin low and high risk patients in Ki67 low, intermediate and high tumors, respectively, and stratified analysis of OS of patients with ki67-values low (≤ 10%)/ intermediate (11-24%)/ high (≥ 25%) and EPclin low risk vs high risk. | 3, 5 and 10 years | 
| DMFS low risk vs. high risk who have /have not been treated according to the S3 and St. Gallen guidelines | Assessment of DMFS after 3, 5 and 10 years of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification. | 3, 5 and 10 years | 
| DFS low risk vs. high risk who have /have not been treated according to the S3 and St. Gallen guidelines | Assessment of DFS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification. | 3, 5 and 10 years | 
| OS low risk vs. high risk who have /have not been treated according to the S3 and St. Gallen guidelines | Assessment of OS of patients with low risk vs. high risk as defined by national (German S3) and international (St. Gallen Consensus) guidelines based on IHC-classification. | 3, 5 and 10 years | 
| Chemotherapy regimens | Description of the given chemotherapy regimens (in all patients and separately for men and women). | 1 year | 
| Given endocrine therapy | Description of the given endocrine therapy (in all patients and separately for men and women). | 10 years | 
| Duration of endocrine therapy | Duration of the endocrine therapy (in all patients and separately for men and women). | 10 years | 
| Proportion of patients with prolonged endocrine therapy | Proportion of patients with EPclin low risk and high risk respectively who received an extended (> 5 years) endocrine therapy in all patients and separately for men and women). | 10 years | 
| DMFS for patients with 5 years of endocrine therapy vs. extended endocrine therapy | Assessment of DMFS according to EPclin / EP risk class for patients who have received an endocrine therapy for 5 years vs. patients who received an extended endocrine therapy (> 5 years). | 10 years | 
| DFS for patients with 5 years of endocrine therapy vs. extended endocrine therapy | Assessment of DFS according to EPclin / EP risk class for patients who have received an endocrine therapy for 5 years vs. patients who received an extended endocrine therapy (> 5 years). | 10 years | 
| OS for patients with 5 years of endocrine therapy vs. extended endocrine therapy | Assessment of OS according to EPclin / EP risk class for patients who have received an endocrine therapy for 5 years vs. patients who received an extended endocrine therapy (> 5 years). | 10 years | 
| Correlation ( pT- and pN data vs. ciT and ciN-data) | Assessment of the correlation between EPclin, that has been calculated with pT- (pathological tumor size) and pN (pathological nodal status) data and the EPclin based on ciT (clinical/ imaging tumor size) and ciN (clinical/imaging nodal status)-data (in all patients and separately for men and women). | 1 year | 
| Concordance ( pT- and pN data vs. ciT and ciN-data) | Assessment of the concordance between EPclin, that has been calculated with pT- and pN data and the EPclin based on ciT and ciN-data (in all patients and separately for men and women). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, EndoPredict®, endocrine therapy