Clinical trial NCT02449993: Re-Examination of Tumor Material and Re-Evaluation of Patient Data From Patients Treated With Neo-adjuvant Therapy
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: diagnostic study
analysis of estrogen receptor
progesterone receptor
Human epidermal growth factor receptor 2
Ki-67
Lead sponsor: BioNTech Diagnostics GmbH
Sponsor class: INDUSTRY
First posted: 2015-05-21
Enrollment: 101
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: See Eligibility Criteria

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline
Secondary outcomes:
measure: 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™
timeFrame: 5 years from the date of patient registration
measure: 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
timeFrame: Baseline
measure: 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)
timeFrame: 5 years from the date of patient registration
Other outcomes:
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