Can we use breast density measurement to indicate whether mammography or MRI can best be used to screen women with familial risk for breast cancer?

Twenty-five percent of all breast cancers are detected before age 50 years. A positive family history is a major risk factor for breast cancer at a young age. In over 75% of the families that display clear clustering of breast cancer no causative mutation in the BRCA1, the BRCA2 or other genes can be detected. Women from these families cannot be tested to distinguish those with high from those with average risk of developing breast cancer.

Tumour stage at detection is of key influence on survival. Therefore Dutch guidelines advise regular breast surveillance to all women with a family history. For women with an estimated cumulative lifetime risk (CLTR) ≥20% yearly mammography between 40 and 50 years is advised. Yearly mammography and specialist clinical examination is advised for women with CLTR ≥30% between 35 and 60 years. Although due to screening tumours might be found at a more favourable tumour stage, screening also causes false-positive test results.

In the last decade several screening trials have been completed and MRI had a significant higher sensitivity than mammography in all studies. However in most studies MRI gave significantly more false-positive results and mammography had better sensitivity for Ductal Carcinoma in Situ (DCIS). Nevertheless for BRCA1/2 mutation carriers, who have a CLTR of 40-70%, screening with yearly MRI has been shown cost-effective.

For the larger group of women with familial risk, but without a proven BRCA1/2 mutation it is not clear whether additional MRI is advantageous for some: no separate cost-effectiveness results have been published yet. Since previous screening studies have performed MRI and mammography simultaneously the difference in stage of the tumours when detected by mammography alone is not known. A randomized controlled trial is needed therefore.
Apart from family history and age high density of the breast tissue is the best documented and most important risk factor for breast cancer. Breast density may also strongly influence screening-results:

1. It increases breast cancer incidence significantly, but;

2. Decreases the sensitivity of mammography, though not of MRI, while;

3. False-positive findings at mammography may increase.

High breast density is prevalent in 60% of women below age 50.



Breast density may be the best predictor whether a woman with high familial breast cancer risk can be screened most effectively with mammography or MRI. If proven, breast density measurement can be used to apply the most effective screening tool to screen women with increased risk for breast cancer.

A proportion of women with high familial breast cancer risk can be screened most effectively with MRI. Breast density may be the best predictor whether to screen this particular group of women with mammography or MRI.

N/A

1. MRI with clinical examination yearly + mammography every other year (year 1 + 3) (n=1000;

2. Mammography with clinical examination yearly (n=1000).