Assessment of Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in ER-positive, Her2-negative Early Breast Cancer
Assessment of Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in ER-positive, Her2-negative Early Breast Cancer
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.
Inclusion Criteria:

 1. Woman, Age ≥ 18 years;

 2. Performance status 0 or 1 (according to World Health Organization criteria);

 3. 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)

 4. Fully operated breast cancer including complete resection of breast tumor and adequate
 axillary surgery;

 5. Available surgical material (formalin-fixed, paraffin-embedded) for genomic test
 evaluation;

 6. ER-positive by immuno-histochemical (>10% cells stained or Allred Score≥4);

 7. HER2-negative by IHC (score 0 or 1+) and/or fluorescence in situ hybridization/silver
 in situ hybridization/chemiluminescent in situ hybridization ;

 8. 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

 9. Adequate renal, hepatic, cardiac and hematopoietic functions for a chemotherapy
 administration;

 10. Willingness and ability to comply with scheduled visits as well as with test results
 and chemotherapy decision according to the latest;

 11. Signed informed consent and Health insurance coverage.

 Exclusion Criteria:

 1. Non operable, bilateral, locally advanced, T4 or metastatic breast cancer;

 2. HER2 Overexpression, as assessed by 3+ IHC or FISH/SISH/CISH amplification;

 3. 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;

 4. Any previous systemic or locoregional treatment for the present breast cancer;

 5. Documented inherited predisposition with BRCA1/2 or TP53 mutation;

 6. Previous hormone replacement therapy (HRT) stopped less than 2 weeks before surgery;

 7. Previous treatment for the present breast cancer;

 8. Person unable to give informed consent.