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It’s in the Genes: Breast Density, Microcalcifications, and Masses Can Be Inherited


Study shows three risk factors for breast cancer can be passed down through genes.

Dense breast tissue, microcalcifications, and masses. They’re all significant risk factors for breast cancer that can be visualized in a mammogram – and according to new research, they’re also risk factors that can be inherited.

In a study published on April 2 in Cancer Research, a team, led by Natalie Holowko, Ph.D., from the medical epidemiology and biostatistics department at the Karolinska Institutet in Stockholm, investigated the link between these factors and a woman’s genetic predisposition for developing breast cancer.

“Our results are important given that [mammographic density], microcalcifications, and masses are strongly associated with breast cancer. Furthermore, little is known of the biology behind any of these three traits,” Holowko wrote. “A better understanding of mammographic feature might lead to further efforts aimed at improving how they are measured, and thus lead to improvements in breast cancer detection.”

This is the first study to outline heritability estimates for mammographic density, microcalcifications, and masses, the authors report.

To better understand the heritability of these key features, Holowko’s team examined full-field mammography results, genetic data, and survey question answers from 56,820 women, ages 40 to 75, who received imaging at one of four Swedish hospitals between January 2011 and March 2013. The women had no prior history of breast cancer, breast enlargement, or breast reduction. The team also included 3,880 sisters, both full- and half-siblings.

Based on the team’s calculations, after adjusting for outside risk factors, the heritability of breast density was estimated to be 58 percent. This finding is similar to the results of previous research.

“The strong heritability of [mammographic density] also highlights the importance of further investigating shared loci contributing to both [mammographic density] and breast cancer, to better understand the etiology of the disease and mechanisms through which [mammographic density] influences breast cancer risk,” she wrote.

In addition, they identified a 23-percent heritability for microcalcifications. While both the polygenic risk score and family history were positively associated with microcalcifications, the team noted the association of lifestyle factors, such as hormone replacement therapy and alcohol intake, and genetics with microcalcifications remains unclear.

A 13-percent heritability was discovered with masses, but they did not discover any significant associations between a family history of breast cancer and the number of masses.

The researchers also delved deeper to identify how similar the findings were between siblings. According to their results, full siblings were more apt to have similar findings for breast density, microcalcifications, and masses than peers who weren’t siblings. Half-siblings also had similar microcalcification and mass findings. Among that group, however, the results were stronger for women who shared a mother than those who shared a father.

“For [mammographic density] and masses, the correlations between materal half-siblings was higher than between paternal half-siblings, potentially indicating a small component attributable to the shared environment,” they wrote.

The authors did note that other individual and environment risk factors do play a role in the development of dense breast tissue, microcalcifications, and masses. They pointed to the need for further research into the genetic and non-genetic factors that are associated with these three features that are seen on mammograms.

“Breast features identified through mammography are important for identifying women at high risk for developing breast cancer in the short term,” Holowko said in a press statement. “It is important to understand the genetic determinants of these traits, as the underlying mechanisms for their association with breast cancer is not well understood.”

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