Trial Information

Clinical and Biological Characterization of Male Breast Cancer: An International Retrospective EORTC, BIG and NABCG Intergroup Study

OBJECTIVES:

Primary

- To perform a large international joint retrospective analysis of clinical and
biological data of male breast cancer (BC) patients treated in the last 20 years.

- To create a database of patient characteristics, disease features, treatments received,
and clinical outcomes of a large series of men diagnosed with BC over the last 20 years
in centers in Europe, America, and third countries.

- To perform a central pathological review of the corresponding large series of male BC
tumors to determine their biologic characteristics and identify relevant prognostic and
predictive markers.

Secondary

- Provide important information regarding male BC and set the scene for a second phase
that is a prospective, international, multicenter, registry of male BC with concomitant
material collection that will enable us to decide if a clinical trial is feasible for
male BC patients.

- To characterize the histologic, pathologic, and molecular features of male BC.

Tertiary

- To correlate biomarker status with baseline clinicopathologic variables and patient
outcome using multivariable analysis.

- To perform IHC for quantitative ER and PgR protein levels, HER-2 status and Ki-67,
using FISH when applicable.

- To construct tissue microarrays derived from the formalin-fixed, paraffin-embedded
tissue specimens.

- To analyze potential biomarkers which either have previously been reported to correlate
with outcome in male BC or are suspected of being of interest in this disease, such as
(but not limited to) androgen receptor, cyclin D1, p21, p27, intratumoral aromatase and
survivin.

- To perform from the available fresh frozen tumor samples, detailed biologic
characterization of male BC using techniques such as enzyme-linked immunosorbent assay
to evaluate uPA-PAI1 and AIB1, the prognostic value of the 70-gene profile and the
wound signature.

- To evaluate by gene expression profiling technology the presence and relative incidence
of the BC biologic subtypes (basal-like, Luminal A and B, HER-2 positive) as well as
the presence and clinical significance of "intrinsic" subtype performed by PAM 50
assay.

- To identify and select biomarkers that should be incorporated in the prospective study.

OUTLINE: This is a multicenter study. Patients are stratified according to disease extent
(metastatic vs non-metastatic).

Patient charts will be reviewed and data entered into a database. Data will be collected on
patient epidemiology (e.g., age, ethnicity), possible risk factors (e.g., family history of
cancer, chronic liver disease, obesity), and tumor characteristics (e.g., pathologic size,
lymph node involvement, stage of disease, tumor grade, ER and PgR status, HER2
over-expression and results of BRCA 1 and 2 testing). Information regarding surgical
therapy, radiotherapy, chemotherapy, and endocrine therapy will be collected. Patient
outcomes, (e.g., disease recurrence or progression, new primary cancer, and overall
survival) will be noted.

Tumor blocks must be collected and sent to central laboratories in United States (US
samples) and in United Kingdom (Europe and the rest of the world samples) for central
pathology assessment of several biomarkers in formalin-fixed, paraffin-embedded tissue.
Fresh frozen tumor samples, when available, will be requested and analyzed in laboratories
in Netherlands and US.