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.
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- UNICANCER
- 主要终点
- Comparison of genomic tests clinical utility
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Endopredict®
genomic test Endopredict® realized on surgery tumour samples
干预措施: Genomic test (Diagnostic Test)
Prosigna®
genomic test Prosigna® realized on surgery tumour samples
干预措施: Genomic test (Diagnostic Test)
OncotypeDX®
genomic test OncotypeDX® realized on surgery tumour samples
干预措施: Genomic test (Diagnostic Test)
Mammaprint® assay
genomic test Mammaprint® assay realized on surgery tumour samples
干预措施: Genomic test (Diagnostic Test)
结局指标
主要结局
Comparison of genomic tests clinical utility
时间窗: 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)
次要结局
- 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)