The TESTBREAST study: early detection of breast cancer in women at high risk of developing breast cancer with serum biomarkers.

There is need to improve screening for early detection of breast cancer. In
population screening with standard mammography one out of five cancer cases is
missed. In surveillance of (hereditary) high risk groups this number is even
considerably higher (one in two) with high numbers of interval cancers reported
and screen detected lesions with unfavorable size. Family history is one of the
most influencing risk factors in breast cancer development.
Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas with
two high-penetrance genes (BRCA1 and BRCA2) responsible for about 16% of the
familial risk of breast cancer cases and associated with an 60-80% lifetime
risk for a mutation carrier. Early detection strategies are considered to
address this heightened risk.
The purpose of a screening program is to identify breast cancer at an early
stage before (regional) metastatic spread. The survival of women diagnosed with
breast cancers <1 cm and with negative lymph nodes is excellent. In BRCA
mutation carriers and in familial high-risk patients, tumor size at detection
is a key predictor of survival and mortality risk may be reduced by early tumor
detection. Early detection in high risk patients can improve survival time from
75% to 93%.(1)
Mammography has a low performance in this group with only 30-40% sensitivity.
The use of MRI next to mammography may improve the sensitivity of screening in
women with a familial or genetic predisposition to breast cancer but the
specificity is variable, the technique is time consuming and demanding and
costs are high. In a recent study it was shown that 10% of the DCIS tumors were
missed by using solely MRI data.(2)
A specific and more sensitive alternative to these image based techniques could
be the use of proteomic or glycomic biomarkers

Early detecction of breast cancer in women with high risk of developing breast
cancer with protein and glycan biomarkers.

Serum samples are obtained from high risk women (familial or BRCA or CHECK2
mutation carriers) visiting the outpatient clinic for regular screening. On
average 2 samples are colected per year, dependent on regular screeningmoments.
The process of blood collection, storage en processing is standardized. De
protein and/or glycan profiles in serum are analysed with 'Matrix- assisted
Laser Desorption Ionization Time-Of-Flight' Mass Spectrometer(MALDI- TOF) or
'Matrix Assisted Laser Desorption Ionization Fourier Transform Ion Cyclotron
Resonance' Mass Spectrometer (MALDI-FT-ICR) or Orbitrap. The obtained high
throughput profiles are statistical evaluated.

The burden is multiple times vena punction (average of 2 times per year) and
answer twelve multiple choice questions.