Large Norwegian mammography study: More breast cancer among women with dense breast tissue

A new, large study from the Norwegian Mammography Programme confirms that women with dense glandular tissue have a higher risk of developing breast cancer than women with high-fat breasts.

Published: 26.06.2018, updated 07.08.2018

The study is unique in that it used automatic measurement of mammographic breast density, which could have great significance for future screening, the researchers behind the study believe.

The research group used automated software to classify mammographic density among about 100,000 women, aged 50 to 69 years, who participated in the Mammography Programme in the period 2007 to 2015.

This provided data from more than 300,000 screening studies, making this clearly the largest study ever conducted in the field.

"We found both that the risk of being diagnosed with breast cancer, and of having to undergo additional examinations, was higher among the women who were classified with dense breast tissue than among those who were classified with non-dense breast tissue," says Professor Solveig Hofvind at the Cancer Registry of Norway, national leader of the Mammography Programme and leader of the research group behind the study.

"The study confirms findings from previous research and tells us that the automated method we used worked as intended," she explains. 

Dense glandular tissue masks tumors

The term «dense breasts» refers more precisely to the term «mammographic density», which is used in diagnostic imaging to say something about how much dense glandular tissue and how much fatty tissue is present in the breast. Neither the woman herself nor a doctor will be able to sense how dense the breasts are – it can only be seen and determined from mammography images.

In a mammography image, adipose tissue is presented as black or dark grey, while dense glandular tissue appears white or light grey. The challenge is that cancerous tumours in the breast also turn white or light grey on mammography images.

This means that when the glandular tissue is clogged, a tumor can be hidden and the possibility of detecting breast cancer is reduced. In addition, it is known that women with very dense breasts have a higher risk of developing breast cancer than those who have high-fat, or non-dense breasts.

(Story continues below photo)

The picture shows breasts with different densities, where A is most fat-rich while D is most glandular, i.e. has high mammographic density. Photo: Radiology Assistant

This work has recently been published in the renowned American journal Radiology by a research group affiliated with the Mammography Programme, a screening programme operated and quality assured by the Cancer Registry. Doctor and PhD Nataliia Moshina at the Cancer Registry of Norway was the first author of the study.

Doubled risk of cancer between screening rounds

Dr. Moshina explains that they divided the women in the study into two groups, those with "dense" and those with "non-dense" breasts. Those with dense breasts accounted for 28 per cent of the screening examinations.

In this material, they found that the proportion of breast cancer detected by screening was 6.7 per 1000 examinations for women with dense breasts and 5.5 per 1000 for women with non-dense breasts.

The proportion of interval cancer, i.e. breast cancer detected between two planned screening examinations, was 2.8 per 1000 in the group with dense breast tissue, while it was only 1.2 per 1000 among women who did not have dense breast tissue.

The study also showed that the sensitivity of the Mammography Programme for detecting breast cancer among women with dense breasts was 71 percent, compared to 82 percent for women with non-dense breasts.

The researchers additionally found that the breast cancer cases detected by screening were more advanced among the women with dense breasts; The mean diameter of the tumours was 16.6 mm in these, compared to 15.1 mm in the non-dense group.

A similar difference was observed in terms of spread to lymph nodes, another important marker of breast cancer prognosis; 23.5 and 18.2 per cent of the women, respectively, were found to have spread to lymph nodes in the group with dense versus non-dense breasts.

Need more knowledge about the biology of glandular tissue

Professor and pathologist Lars A. Akslen at the Centre for Cancer Biomarkers CCBIO/University of Bergen and Haukeland University Hospital, was also part of the research group behind the study.

He explains the findings by saying that different glandular tissues can provide different growth conditions for the cancer cells, and emphasizes that we need more knowledge to understand the biological role gland density may have in relation to the risk of breast cancer and in relation to tumor characteristics for the individual woman.

Moshina and colleagues also found significant differences between women with dense and non-dense breasts.

The proportion who were called back in for additional examinations because the mammography images showed suspicious findings was 3.6 percent for women with dense breasts, compared with 2.7 percent for women with non-dense breasts.

The proportion who had to undergo a biopsy, i.e. a needle sample of the breast to examine suspicious tissue, was 1.4 percent among those with dense breasts and 1.1 percent among those classified as non-dense.

Want to offer even more precise exploration

As head of the Mammography Programme, Solveig Hofvind nevertheless wants to reassure the 600,000 women in the Mammography Programme's target group, and she emphasizes that the risk of getting breast cancer, and of cancer cases being overlooked, is small after all.

She therefore believes there is every reason to be satisfied with the answer if you are told that there are no signs of breast cancer on the screening examination.

"But no medical examination is perfect. The reason why we invest in this type of research is that we constantly want to improve the service we offer women - that's why we put so much effort into continuously developing the technology we use, and we are constantly committed to increasing our knowledge about the female breast so that we can be even more precise in the search for breast cancer, she explains.

Hofvind further explains that women should also be aware that other factors affect the risk of breast cancer and mammographic density, such as the use of hormones and obesity.

There are therefore many more factors that need to be mapped and investigated before a decision can be made to use results from automated density measurements to determine whether some women need other screening methods, such as ultrasound, tomosynthesis or MRI, in addition to mammography.

She refers to several large ongoing studies both in Norway and in Europe, and is clear that more high-quality studies are still needed before any changes to the current screening services can be implemented.

Attracting interest in the U.S.

The Norwegian study on breast density has received a lot of attention in the United States.

"I think the reason the study is attracting so much interest in the United States is that over half of the states there have already introduced legislation that gives women the right to know whether or not they have 'dense breasts' – despite the fact that good methods for measuring this have not yet been available, either in the United States or in other countries" explains Professor Solveig Hofvind.

Until now, density measurements on mammography images have been based on subjective methods - the individual X-ray doctor's assessment - based on given criteria. The method is uncertain and time-consuming. In addition, it can take away the main focus of breast radiologists, which is to find breast cancer tumors.

"The groundbreaking thing about this study is that we have managed to show that automated methods for measuring breast density from mammography images can be effective and safe," Hofvind explains.

"This is an important step towards showing how automated density measurements can work in modern breast cancer screening programmes – although of course more similar studies will be needed to confirm the results before any decisions to introduce the technology can be made," she elaborates.

Unique Norwegian data

Effective methods for measuring mammographic density so that sorting between those with high and low densities is correct have long been in short supply in mammography screening.

"Dr. Moshina has worked with this topic in her doctoral thesis, and over several years we have acquired knowledge about different measurement methods. This study is a continuation of Moshina's work, and once again puts the Norwegian Mammography Programme on the map in an international perspective," says Hofvind.

"The national model on which the Norwegian programme is based provides unique opportunities for conducting good studies with a large number of screening examinations, as we have done in this study," she continues.      

Hofvind adds that she often encounters international research colleagues who contact her with requests for various collaborative projects because the Norwegian screening programme is well organised, of high quality and has good and complete data.

In this current study, the Cancer Registry's researchers have collaborated with, among others, the renowned University of Washington, Seattle, in the USA.