Breast Density as Indicator for the Use of Mammography or MRI to Screen Women with Familial Risk for Breast Cancer: a RCT.

In the Netherlands and many other countries, it is now recommended that women
with a BRCA1 or 2 mutation are screened by yearly MRI between age 25-60. Less
than 5% of all breast tumours are related to such mutations. Having a clear
family history of breast cancer, but no BRCA1 or 2 mutation, and having dense
breast tissue are both strong breast cancer risk factors conferring high risk
often already at a young age. Currently the Dutch guideline recommends these
women screening with mammography, although sensitivity of MRI was much higher
in all risk and age groups in the Dutch MRISC and comparable international
studies. Especially in women with high mammographic density, in whom breast
cancer risk is highest, the sensitivity of mammography is seriously impaired,
leading to many missed cases. MRI is likely to lead to better detection of
breast tumours in these groups. Breast density is high in 60% of the women
below age 50 yrs. But high mammographic density not only indicates a high
breast cancer risk and decreased performance of mammography, but also more
benign breast disease and therefore potentially more false positive
MRI-results. Cost-effectiveness may thus vary across categories of mammographic
density The limitation of all previous MRI screening studies is that they do
not contain a comparison group; all participants received both MRI and
mammography. Therefore, we cannot empirically assess in which stage tumours
would have been detected by either test or whether MRI would reduce the number
of interval tumours. We need a randomized controlled trials (RCT) to assess the
gain and cost.

To assess, based on a woman*s risk profile, mammographic density and age, the
most cost-effective screening method, mammography or MRI, for women at high
risk.

A Randomised Controlled Trial, comparing a screening strategy where MRI is
added to the practice according to the current guideline for women with high
risk due to family history:
Women aged 30-55 years, with >20% familial CLTR but no known BRCA1 or 2
mutations.
Intervention: *yearly MRI and clinical examination + mammography every other
year*(n=1,000) versus
(current practice) *yearly mammography and clinical examination* (n=1,000).
Results will be stratified by mammographic density to examine whether
cost-effectiveness of the screening strategies is dependent on mammographic
density.

To perform MRI takes about 20 minutes, no extra visit to the centre is needed.
Haematoma may occurr because of the IV gadolinium contrast, for which contrast
few women may be allergic.
Women will be warned that MRI may have more false-positive results, that may
prompt additional ultrasound, fine needle aspiration biopsy or even histologic
biopsy with local anaesthesia.