Mammographic Breast Density, Microcalcifications, and Masses May be Inheritable

Given that these features are associated with breast cancer risk and could improve the detection of short-term risk of breast cancer, the authors suggested that further investigation of common loci is necessary.

In a study published in Cancer Research, researchers confirmed previous findings of heritability in mammographic breast density, and also established heritability of the number of microcalcifications and masses at baseline.1

Given that these features are associated with breast cancer risk and could improve the detection of short-term risk of breast cancer, the authors suggested that further investigation of common loci associated with mammographic features is necessary to better understand the etiology of breast cancer.

“Breast features identified through mammography are important for identifying women at high risk of developing breast cancer in the short term,” Natalie Holowko, PhD, postdoctoral researcher in the department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm, said in a press release.2 “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.”

Using mammographic screening history and detailed questionnaire data from 56,820 women included in the KARMA prospective cohort study, researchers evaluated the association between a genetic predisposition to breast cancer and mammographic features among women with a family history of breast cancer (n = 49,674) and a polygenic risk score (PRS; n = 9,365). Moreover, the heritability of mammographic features such as dense area, microcalcifications, masses, and density change (cm2/year) was estimated using 1,940 sister pairs.

Heritability of mammographic breast density was estimated to be 58% (95% CI, 48%-67%), while the estimated heritability of mammographic density change (MDC) was found to be essentially null (2%; 95% CI, 8%-12%). After full adjustment, the heritability of microcalcifications was estimated at 23% (95% CI, 2%-45%), and masses at 13% (95% CI, 1%-25%). For all of the outcomes, the remaining variance was attributed to the individual or nonshared environment. 

The correlation between a genetic predisposition to breast cancer (using PRS) and mammographic breast density and microcalcifications was positive, whereas for masses it was borderline significant. Additionally, for MDC, having a family history of breast cancer was associated with a somewhat greater mammographic breast density reduction. 

“If we can better understand the mammographic features that are associated with breast cancer risk, then we can aim to improve how these features are measured and hopefully improve early breast cancer detection,” Holowko said.

Given that the researchers did not find any heritability in MDC, they speculate that in addition to genetics, there may be other shared factors between breast cancer and MDC that are important, including hormonal factors. Additionally, while modifiable lifestyle factors such as alcohol intake and HRT are positively associated with mammographic breast density, the association of lifestyle factors and genetics with microcalcifications are not well known. 

“To date, there are approximately 170 breast cancer susceptibility loci identified, with the best- performing breast cancer PRS (used in this study) including 313 SNPs,” the authors wrote. “Further identification of new SNPs associated with breast cancer will also allow us to refine PRSs for the disease, with the combined effect of common breast cancer susceptibility variants being the best indicator of risk.”


1. Holowko N, Eriksson M, Kuja-Halkola R, Azam S, He W, Hall P, Czene K. Heritability of Mammographic Breast Density, Density Change, Microcalcifications, and Masses. Cancer Research. doi:10.1158/0008-5472.CAN-19-2455.

2. Breast density, microcalcifications, and masses may be inheritable traits [news release]. American Association for Cancer Research. Published April 2, 2020. Accessed April 9, 2020.