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

BioNTech Diagnostics GmbH101 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

101

Conditions

Breast Cancer

Interventions

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Baseline

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 5 years from the date of patient registration