Invasive Breast Cancer
Conditions
Keywords
Subtyping of Invasive breast cancer
Brief summary
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.
Detailed description
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.
Interventions
DEVICEMammaTyper™
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.
Sponsors
BioNTech Diagnostics GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Invasive breast cancer verified in a histological biopsy * Age 65 or younger * Estrogen receptor (ER), PgR and HER2 expression have been determined * No distant metastases present (M0) * The patient provides a written informed consent for study participation * The estimated risk of breast cancer recurrence is high (25% or higher within the first 5 years from the date of the diagnosis, over \>35% within the first 10 years from the diagnosis)
Exclusion criteria
* Patients with breast cancer with a special histological type (mucinous, papillary, medullary, or tubular type of breast cancer) when no metastases are present in the ipsilateral axillary lymph nodes * The WHO performance status is moderate/poor, Z \>1 * The peripheral blood leukocyte count is less than 3.0 x 109/L, the blood granulocyte count is less than 1.5 x 109/L, or the blood thrombocyte count is less than 120 x 109/L * Any physical or mental disorder that is considered to prohibit administration of chemotherapy * Cardiac failure; severe cardiac arrythmia requiring regular medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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™ | 5 year from the date of patient randomisation | 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)) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With High Ki-67 and Prognosis on Outcome for DDFS and OS (Measured by Hazard Ratio) | 5 years | High Ki-67 is prognostic for worse outcome for DDFS and OS (measured by hazard ratio) |
| 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 | 5 years | Superiority of outcome prediction for MammaTyper™ Ki-67 over local Ki-67 eyeballed assessment for Luminal tumors with regard to OS and DDFS |
Participant flow
Recruitment details
The clinical data and breast tumour tissue samples were collected within the FinHer trial (identifier ISRCTN76560285), where 1010 women with axillary node-positive or high-risk axillary node-negative breast cancer were randomly assigned between October 2000 and September 2003.
Participants by arm
| Arm | Count |
|---|---|
| FinHer Patients 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. | 1,010 |
| Total | 1,010 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | No cancer tissues available | 241 |
Baseline characteristics
| Characteristic | FinHer Patients |
|---|---|
| Age, Continuous | 50.9 years |
| Region of Enrollment Finland | 1010 participants |
| Sex: Female, Male Female | 1010 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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™
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))
Time frame: 5 year from the date of patient randomisation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luminal A | 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™ | 92 percentage of analyzed participants |
| 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™ | 82 percentage of analyzed participants |
p-value: 0.001895% CI: [0.246, 0.726]Regression, Cox
Secondary
Number of Patients With High Ki-67 and Prognosis on Outcome for DDFS and OS (Measured by Hazard Ratio)
High Ki-67 is prognostic for worse outcome for DDFS and OS (measured by hazard ratio)
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luminal A | Number of Patients With High Ki-67 and Prognosis on Outcome for DDFS and OS (Measured by Hazard Ratio) | 0.42 Hazard ratio |
p-value: 0.00195% CI: [0.25, 0.71]Regression, Cox
Secondary
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
Superiority of outcome prediction for MammaTyper™ Ki-67 over local Ki-67 eyeballed assessment for Luminal tumors with regard to OS and DDFS
Time frame: 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Luminal A | 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 | DDFS (MKI67 mRNA positive - negative) | 0.42 Hazard ratio |
| Luminal A | 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 | DDFS (Ki-67 protein positive - negative) | 0.56 Hazard ratio |
| Combined Subtype | 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 | DDFS (MKI67 mRNA positive - negative) | 0.45 Hazard ratio |
| Combined Subtype | 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 | DDFS (Ki-67 protein positive - negative) | 0.43 Hazard ratio |