Prospective Multicenter Randomized Study Assessing Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in Patients With ER-positive, Her2-negative Early Breast Cancer With Uncertainty on the Indication of Chemotherapy Using Standard Assessments.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- UNICANCER
- Primary Endpoint
- Comparison of genomic tests clinical utility
Study Overview
Brief Summary
The need/benefit of adjuvant chemotherapy could be negligible for a certain category of patient with newly diagnosed unilateral non metastatic breast cancer. Physicians are sometimes divided between the administration of adjuvant treatment and no administration when the risk of distant relapse at 10 years is around 10% with uncertainty and a theoretical benefit of chemotherapy is less than 5% at 10 years according to guidelines in use in the center.
Several genomic tests have been developed this last decade. These tests use a sample of breast cancer tissue to analyze the activity of a group of genes. Knowing whether certain genes are present or absent, overly active or not active enough, can help physicians predict the risk of recurrence.
In addition to standard pathological characteristics, a genomic test could be helpful in making treatment decisions, such as whether or not chemotherapy should be part of the treatment plan. First generation prognostic tests are currently widely used worldwide to guide decision making regarding adjuvant chemotherapy (OncotypeDX™ Mammaprint®). Prognostic tests have reached a level of evidence 1A, with the results of the prospective randomized trial "Mindact". In the "Mindact" trial, among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. The health-economic value of such signatures in the general population of patients with localized breast cancer appears very low at current costs.
Meanwhile, next generation prognostic signatures have been developed that have integrated clinical parameters and suggest high added value beyond all standard and traditional characteristics including tumor burden, grade, Estrogen Receptor (ER) and Progesterone Receptor (PR), Her2, age and also standard assessment of proliferation.
In this study, the clinical utility of genomic tests (Endopredict®, Prosigna®, OncotypeDX®, Mammaprint® assay) defined as impact on chemotherapy decision in the adjuvant setting in patients with ER-positive, Her2-negative early breast cancer with uncertainty on the indication of chemotherapy using standard assessments will be compared.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Woman, Age ≥ 18 years;
- •Performance status 0 or 1 (according to World Health Organization criteria);
- •Patient with newly diagnosed, unilateral, localized, histologically confirmed, invasive breast cancer; Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all are ER > 10% or Allred ≥ 4, Her2-negative (genomic test will be performed on the lesion considered the most pertinent by the multidisciplinary team)
- •Fully operated breast cancer including complete resection of breast tumor and adequate axillary surgery;
- •Available surgical material (formalin-fixed, paraffin-embedded) for genomic test evaluation;
- •ER-positive by immuno-histochemical (>10% cells stained or Allred Score≥4);
- •HER2-negative by IHC (score 0 or 1+) and/or fluorescence in situ hybridization/silver in situ hybridization/chemiluminescent in situ hybridization ;
- •Uncertainty regarding the toxicity/benefit of adjuvant chemotherapy, outlined in the following situations:
- •Grade 1: pT3 or 1-3 node positive
- •Grade 2: pT1 pN0 but high proliferation (Ki67 >20%) or lympho-vascular emboli, or 1-3 node positive
- •Grade 2 : pT2 pN0
- •Grade 3: pT1 pN0
- •Adequate renal, hepatic, cardiac and hematopoietic functions for a chemotherapy administration;
- •Willingness and ability to comply with scheduled visits as well as with test results and chemotherapy decision according to the latest;
- •Signed informed consent and Health insurance coverage.
Exclusion Criteria
- •Non operable, bilateral, locally advanced, T4 or metastatic breast cancer;
- •HER2 Overexpression, as assessed by 3+ IHC or FISH/SISH/CISH amplification;
- •Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma;
- •Any previous systemic or locoregional treatment for the present breast cancer;
- •Documented inherited predisposition with BRCA1/2 or TP53 mutation;
- •Previous hormone replacement therapy (HRT) stopped less than 2 weeks before surgery;
- •Previous treatment for the present breast cancer;
- •Person unable to give informed consent.
Arms & Interventions
Endopredict®
genomic test Endopredict® realized on surgery tumour samples
Intervention: Genomic test (Diagnostic Test)
Prosigna®
genomic test Prosigna® realized on surgery tumour samples
Intervention: Genomic test (Diagnostic Test)
OncotypeDX®
genomic test OncotypeDX® realized on surgery tumour samples
Intervention: Genomic test (Diagnostic Test)
Mammaprint® assay
genomic test Mammaprint® assay realized on surgery tumour samples
Intervention: Genomic test (Diagnostic Test)
Outcomes
Primary Outcomes
Comparison of genomic tests clinical utility
Time Frame: At the end of the inclusion period: 12 months
Pairwise comparisons between genomic tests in terms of percentage of changes between initial adjuvant chemotherapy decision and final receipt of chemotherapy (yes/no)
Secondary Outcomes
- Distant disease-free survival in patients who do not receive chemotherapy(5 years)
- Distant disease-free survival in patients who do not receive chemotherapy based on genomic test result.(5 years)
- Reason for discordant final decision when they occur(12 months)
- Feasibility of test in terms of time interval.(12 months)
- differences in results between local and central reading of ER, PR, Her2 and Ki67(12 months)
- Change of therapy based on the genomic test findings in a virtual tumour board(12 months)
- Evaluation of the cost effectiveness of genomic tests(5 years)