Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Estrogens

Mitogens

Progesterone

MammaTyper™ will be used to assess tumor material of patients treated with neo-adjuvant therapy.

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).

MammaTyper™

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.

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.

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

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

For each MammaTyper and immunohistochemical based subtype categorization, percent agreement, positive and negative percent agreement as well as kappa-statistics are calculated.

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

Assessed as rate of patients with complete response and Ki-67 determination according to MammaTyper and visual scoring assessment

Assessed as rate of patients with 5 year OS and high or low expression of ESR1 mRNA

BioNTech Diagnostics GmbH

MammaTyper™ kit will be used tio assess tumor material of patients enrolled into the FinHer trial.

MammaTyper™ kit is a molecular in vitro diagnostic test for the quantitative detection of the ribonuclease acid (RNA) expression status of the genes for estrogen receptor (ESR1), progesterone receptor (PGR), human epidermal growth factor receptor 2 (HER2) and proliferation antigen KI 67.

Michael Oed, Dr.

This is a prospective examination of tumor material of breast cancer patients randomized into the FinHer-trial (= (= Comparison of vinorelbine and docetaxel and trastuzumab as adjuvant treatments of breast cancer patients wirh a high risk of cancer recurrence).

The formalin-fixed, paraffin-embedded tissue samples will be analysed for Estrogen receptor 1 (ESR1), progesterone receptor (PgR), Human epidermal growth factor receptor 2 (HER2) and Antigen Ki-67 (Ki-67) with the molecular in vitro diagnostic kit MammaTyper™.

According to the new subtyping the 5 year Distant disease free survival (DDFS) and Overall survival (OS) will be re-evaluated.

Despite the fact that reliable measures for the markers ESR1, PgR, HER2, Ki-67 are necessary with the currently used methods up to 20% of determinations are inaccurate and especially Ki67- measures are not very reproducible. Therefore new evaluation systems or new methods are necessary to improve diagnostic.

At least 4 subtypes can be distinguished to date depending on the expression of ESR, PgR, Her2 and Ki-67:

* Luminal A-type
* Luminal B-type
* Her2-type
* Triple-negative-type

MammaTyper™ uses a new approach. Instead of detection of the marker proteins, the messenger ribonucleic adic (mRNA) of marker proteins is quantitated. This prospectively planned diagnostic study will investigate the potential of subgrouping of patients at baseline according to results of MammaTyper™ methodology for predicting survival.

Patients will be subgrouped according to the new marker determination and the DDFS and OS will be evaluated and compared to the DDFS and OS of subgrouping with former marker determination.

Re-Evaluation of Tumor Samples From Women With Breast Cancer With the in Vitro Diagnostic Kit "MammaTyperTM"

Evaluation of the MammaTyperTM Kit, Ref 90020/90021 Performed on Clinical Material Obtained From Patients With Breast Cancer: Re-Examination of Tumor Material and Re-Evaluation of Patient Data of the FinHer-Study

Tumor material of breast cancer patients will be newly assessed by MammaTyper™ and 5 year DDFS will be calculated new according to new subgrouping (Luminal A vs. combined subgroup (Luminal B, HER2 positive, triple negative))

High Ki-67 is prognostic for worse outcome for DDFS and OS (measured by hazard ratio)

Superiority of outcome prediction for MammaTyper™ Ki-67 over local Ki-67 eyeballed assessment for Luminal tumors with regard to OS and DDFS

Since only tumor material was used, adverse events were not documented within the MammaTyper Study

Of all patients, FFPE tumour block was processed with the RNXtract RNA extraction kit (BioNTech Diagnostics GmbH, Mainz) using a magnetic particle-based assay (Supplemental file 1A).

RT-qPCR was done with the MammaTyper kit (BioNTech Diagnostics GmbH, Mainz) for ESR1, PGR, ERBB2 and MKI67.

FinHer Patients

Age, Continuous

Sex: Female, Male

Finland

Region of Enrollment

Clinical data and breast tumour tissue samples were collected within the FinHer trial (identifier ISRCTN76560285).

Dr. Michael Oed

Patients subtyped as Luminal A with DDFS determined 5 years after randomisation

Luminal A

Patients subtyped as Luminal B, HER2 positive, triple negative with DDFS determined 5 years after randomisation

Combined Subtype

5 Year Distant Disease Free Survival (DDFS) Assessed as Rate of Patients Without Distant Metastases in Subgroup Luminal A vs. Combined Subgroup (Luminal B, HER2 Positive, Triple Negative), Based on Subtyping With MammaTyper™

Patients With MKI67 mRNA Determination

Number of Patients With High Ki-67 and Prognosis on Outcome for DDFS and OS (Measured by Hazard Ratio)

DDFS (MKI67 mRNA positive - negative)

DDFS (Ki-67 protein positive - negative)

Determination of DDFS of patients according to MKI67 mRNA (RT-qPCR) and Ki-67 protein (IHC) levels

DDFS According to MKI67 mRNA and Ki-67 Protein (IHC) Levels

Determination of OS of patients according to MKI67 mRNA (RT-qPCR) and Ki-67 protein (IHC) levels

OS According to MKI67 mRNA and Ki-67 Protein (IHC) Levels

Number of Patients With Ki-67 Determined by MammaTyper™ Compared to Local Ki-67 Eyeballed Assessment for Luminal Tumors and Correlation to Rate of Patients With Regard to OS and DDFS

MammaTyper™ kit will be used to assess tumor material of patients enrolled into the FinHer trial.

MammaTyper™: MammaTyper™ kit is a molecular in vitro diagnostic test for the quantitative detection of the ribonuclease acid (RNA) expression status of the genes for estrogen receptor (ESR1), progesterone receptor (PGR), human epidermal growth factor receptor 2 (HER2) and proliferation antigen KI 67.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Re-Examination of Tumor Material and Re-Evaluation of Patient Data From Patients Treated With Neo-adjuvant Therapy	NCT02449993	Breast Cancer	MammaTyper™	18 Years - 70 Years	BioNTech Diagnostics GmbH
Re-Evaluation of Tumor Samples From Women With Breast Cancer With the in Vitro Diagnostic Kit "MammaTyperTM"	NCT02244580	Invasive Breast...	MammaTyper™	18 Years - 65 Years	BioNTech Diagnostics GmbH
Re-Evaluation of Tumor Samples From Women With Breast Cancer With the in Vitro Diagnostic Kit "MammaTyperTM"	NCT02244580	Invasive Breast...	MammaTyper™	18 Years - 65 Years	BioNTech Diagnostics GmbH
Re-Examination of Tumor Material and Re-Evaluation of Patient Data From Patients Treated With Neo-adjuvant Therapy	NCT02449993	Breast Cancer	MammaTyper™	18 Years - 70 Years	BioNTech Diagnostics GmbH

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