Re-Examination of Tumor Material and Re-Evaluation of Patient Data From Patients Treated With Neo-adjuvant Therapy

Study Overview
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Brief Summary
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This is a prospective examination of ribonucleic acid (RNA) extracted from tumor material of breast cancer patients treated with a neo-adjuvant therapy. The RNA will be analysed for expression of estrogen receptor (ER 1), progesterone receptor (PgR), HER2 and Ki-67 with MammaTyper™. According to the determined values for the individual parameters at least 4 subtypes can be distinguished to date Luminal A-type Luminal B-type HER2-type Triple-negative-type As non-clinical endpoint, the agreement of new subtyping with Immunohistochemical methods will be evaluated. As clinical objective, the 5 year Distant metastasis free survival (DMFS) and Overall survival (OS) will be reevaluated according to the new subtyping.

Detailed Description
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Tumor material collected from patients who received neoadjuvant therapy either with four cycles of doxorubicin 60 mg/m² plus pemetrexed 500 mg/m² on day 1 every 21 days followed by four cycles of docetaxel 100 mg/m² on day 1 every 21 days or four cycles of doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² on day 1 every 21 days followed by four cycles of docetaxel 100 mg/m² on day 1 every 21 days will be re-analyzed with the MammaTyper Kit. The Kit is an in-vitro molecular diagnostic test for molecular subtyping of breast cancers into Luminal A & B, HER2 and Triple negative. It allows quantitative detection of the RNA expression status of the genes for estrogen receptor (ESR1), PgR, HER2 and Ki-67 on the basis of their mRNA present in the samples. This prospective diagnostic study will investigate the subtyping-results of the MammaTyper™ analysis and will compare them to the subtyping of the former immunohistochemical analysis performed. Based on the MammaTyper™-subtypes the efficiency of the therapy regimen and the outcome will be re-evaluated from the patient data.

Official Title
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Evaluation of the MammaTyper Kit, Ref 90020/90021 Performed on Clinical Material Obtained From Patients With Early Breast Cancer: Re-Examination of Tumor Material and Re-Evaluation of Patient Data From Patients Treated With Neo-adjuvant Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: MammaTyper™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18-70 years with histologically confirmed primary invasive breast cancer stages T2-T4/N0-N2/M0 with a tumor size of ≥ 2 cm as measured by ultrasound The patient provides a written informed consent for analysis of tumor material Exclusion Criteria: Prior anticancer therapy with an anthracycline or other prior antitumor therapy for breast cancer Inflammatory or exulcerating breast cancer A second primary malignancy [except carcinoma in situ (CIS) of the cervix or adequately treated nonmelanoma skin cancer] unless diagnosed and treated ≥ 5 years ago with no evidence of recurrence Any serious concomitant systemic disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| MammaTyper™<br>MammaTyper™ will be used to assess tumor material of patients treated with neo-adjuvant therapy. | Device: MammaTyper™<br>* MammaTyper™ is an in vitro molecular diagnostic test for the quantitative detection of the biomarkers estrogen receptor (ESR1), progesterone receptor ( PgR), Human epidermal growth factor receptor 2 (HER2) and proliferation antigen Ki-67 on the basis of the values of the messenger ribonucleic acid (mRNA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agreement of new subtyping assessed as rate of patients in MammaTyper-subtype groups compared to rate of patients in subtype groups according to immunohistochemical analysis according to St. Gallen Guideline 2013 | For each MammaTyper and immunohistochemical based subtype categorization, percent agreement, positive and negative percent agreement as well as kappa-statistics are calculated. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess difference of 5 year OS of breast cancer subgroup Luminal A vs. combined subgroup (Luminal B (HER2 positive / HER2 negative), HER2 positive, triple negative), based on subtyping with MammaTyper™ | Assessed as rate of patients in subgroup Luminal A with 5 year OS vs. rate of patients in combined subgroups with 5 year OS based on MammaTyper subtyping | 5 years from the date of patient registration | 
| Estimation of difference in prediction of pathologic complete remission for MammaTyperTM Ki-67 vs. local Ki-67 visual scoring assessment for Luminal tumors, whereby a positive difference is expected | Assessed as rate of patients with complete response and Ki-67 determination according to MammaTyper and visual scoring assessment | Baseline | 
| ESR1 mRNA is predictive for 5 year OS with low expression of ESR1 mRNA being associated with adverse outcome (rate of patients with 5 year OS and high or low expression of ESR1 mRNA) | Assessed as rate of patients with 5 year OS and high or low expression of ESR1 mRNA | 5 years from the date of patient registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diagnostic study, analysis of estrogen receptor, progesterone receptor, Human epidermal growth factor receptor 2, Ki-67