Breast cancer screening more personalized?

Could we detect breast cancer earlier in women with very dense breast tissue if they would also receive a contrast mammography (CEM) or accelerated MRI scan during the population screening? UMC Utrecht is now leading a large trial population study in order to answer that question: DENSE-2.

On Tuesday 14 January 2025, this article has been updated with the latest information. 

Every two to three years, Dutch women between 50 and 75 years old can participate in the national breast cancer screening. They then receive a mammogram in order to detect breast cancer early.

In about 8 percent of these women, a mammogram is not sufficient because they have very dense breast tissue. That means most of their breasts are made up of mammary glands and connective tissue, and they have less fatty tissue in their breasts. As a result, tumors in these women’s breasts are harder to find on a mammogram. This is a problem because females with very dense breast tissue are more likely to get breast cancer than women with a lot of fatty tissue in their breasts.

In very dense breast tissue, about 60 percent of tumors are detected in the population screening, compared to 70 to 85 percent in women with other breast density. So, it is and remains important to participate in the regular population screening, but at the same time researchers are looking for for an additional method to detect breast cancer earlier in case of very dense breast tissue. And this is precisely why this new pilot population study has taken off.

DENSE-1: complementary MRI scan

How could tumors actually be found earlier in very dense breast tissue? One solution could be to offer this group of women an additional MRI scan or contrast mammography during the breast cancer screening, after their initial mammoagraphy has shown that they have very dense breast tissue.

The pros and cons of an additional, extended MRI scan were previously examined during the extensive DENSE-1 study, which was also coordinated by UMC Utrecht. In this study, some 5,000 women with very dense breast tissue were followed during the population screenings between 2011 and 2020. They also received an additional MRI scan. The outcomes of this group were compared with those who were only offered a mammogram during the regular population screening.

Conclusions of DENSE-1: in women with very dense breast tissue, cancer was indeed detected more often and more quickly if they had also received an MRI scan. Tumors were also found at an earlier stage, making them more treatable. Furthermore, the use of MRI was also found to be cost-effective.

Investigate alternative first

If tens of thousands of women are to receive an MRI in a hospital each year, it would require additional equipment and staff. This could lead to capacity problems.

The Dutch Health Council therefore advised the Dutch minister of Health, Welfare and Sports to first investigate an alternative to MRI: contrast mammography (CEM). In contrast mammography, an iodinated contrast medium is injected before the mammogram is taken. As with an MRI, tumors absorb the contrast agent faster, making them more visible than on a normal mammogram. A CEM also takes less time and is therefore less expensive than a regular MRI scan.

DENSE-2: contrast mammogram and/or accelerated MRI?

Effective per July 1, 2024, the minister licensed UMC Utrecht to start and coordinate a second pilot population study: DENSE-2. 15 hospitals throughout the Netherlands are collaborating on this with Bevolkingsonderzoek Nederland and Borstkankervereniging Nederland.

In DENSE-2, researchers are not only looking into the possibilities of contrast mammography but also into those of an accelerated MRI. A normal MRI takes about 20 to 30 minutes to make, while the accelerated version is finished in only five to six minutes (just as quick as CEM).

Carla van Gils is professor of clinical epidemiology of cancer at UMC Utrecht. She was in charge of the first DENSE study and is now also coordinating the new pilot population study. “With this study, we now hope to really change something for the screening of women with very dense breast tissue. The breast cancer population screening is important to detect the illness as early as possible, but with this group it does not work as well,” Carla says. “In DENSE-1, we showed that MRI works for women with very dense breast tissue, but MRI was not considered future-proof due to costs and required capacity. Contrast mammography and accelerated MRI could offer a solution.”

More personalized population screening

DENSE-2 was launched in late 2024. After their mammogram has revealed they have very dense breast tissue, a group of women will be invited for additional screening with a CEM. Another group of women with very dense breast tissue will be invited for an additional accelerated MRI scan.

In both groups, 3,500 women with dense breasts are needed to make the research project valid. Therefore, the researchers expect that they’ll have to invite 6,000 women with very dense breast tissue per group, taking into account, for example, women who will not or cannot participate. The results of both groups will be compared with those of women with dense breasts following the regular population screening: only a mammogram and no additional screening.

Wouter Veldhuis is a mamma-radiologist and associate professor at UMC Utrecht. He is the coordinating radiologist of DENSE-2. “CEM and accelerated MRI are two fantastic techniques, which are both much faster and less expensive than the normal MRI studied in DENSE-1,” Wouter says. “I hope that we are going to show that both techniques are nevertheless just as good at finding tumors. We could then start to use both additionally and thus offer a better and more personalized population screening.”

The DENSE-2 trial will take seven years. The researchers hope to reach a clear conclusion on how good each of the two options is for early detection of breast cancer in women with very dense breast tissue.