Bottom Line: An analysis of a large Swedish cohort revealed that breast density, microcalcifications, and masses are heritable features, and that breast density and microcalcifications were positively associated with a genetic predisposition to breast cancer.
Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research
Author: Natalie Holowko, PhD, postdoctoral researcher in the department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm
Background: "Breast features identified through mammography are important for identifying women at high risk of developing breast cancer in the short term," said Holowko. "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."
Holowko explained that the heritability of breast cancer is roughly 30 percent, and previous studies have estimated that the heritability of breast density is roughly 60 percent. While breast cancer and breast density have overlapping single nucleotide polymorphisms (SNPs), the heritability of other mammographic features, such as microcalcifications, masses, or breast density change, have not been previously reported, she noted. "We wanted to study the heritability of these traits, as this could help us identify important loci for breast cancer susceptibility, which could be used to better identify women who are at increased risk for developing breast cancer," Holowko said.
How the Study was Conducted: Holowko and colleagues evaluated mammographic screening history and detailed questionnaire data from the KARMA prospective cohort study in Sweden. Women were enrolled between January 2011 and March 2013; mammograms were continually collected and participants were followed for diagnosis of breast cancer. Women younger than 40 or older than 75 years were excluded, as were women with a prior breast cancer diagnosis, breast enlargement, or breast reduction. The data cutoff was October 2017.
Results: The researchers calculated the heritability of four mammographic features - breast density, average density change per year (cm2/year), microcalcifications, and masses - using 1,940 sister pairs. The heritability of breast density was estimated to be 58 percent, similar to previously reported findings. The heritability of microcalcifications and masses were estimated to be 23 percent and 13 percent, respectively. Breast density change was not determined to be an inherited trait.
Holowko and colleagues investigated the associations between mammographic features and genetic predisposition to breast cancer, as determined by a polygenic risk score (PRS), among 9,365 women in the KARMA cohort. They found statistically significant positive associations between PRS quintiles and breast density and microcalcifications.
Author's Comments: "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.
Study Limitations: "We identified some limitations with modeling assumptions for density change, however, sensitivity analyses indicated almost no heritability, so we believe the presented results are reliable," noted Holowko.
Funding & Disclosures: This study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Stockholm County Council. Holowko declares no conflicts of interest.
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes 46,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 127 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 22,500 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.