Family History of Breast Cancer, Breast Density May Be Linked

This study investigated the relationships seen among premenopausal women with a family history of breast cancer and their breast tissue density as seen at their annual mammographic screening.

A potential link has been found among premenopausal women between their mammography-determined breast cancer and having a family history of the disease, with the investigators of a new study in JAMA Network Open ultimately stressing the importance of initiating annual screening mammograms at an earlier age in this patient population.

“Family history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood,” they wrote. “Our primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set).”

The 14,415 women in the study consisted of a discovery cohort (n = 375) whose data were collected between December 2015 and October 2016 and a validation cohort (n = 14,040) whose data were collected between June 2010 and December 2015. All data were analyzed from June 2018 through June 2020. Mean ages were similar among these cohorts and between those with and without a FHBC: 47.1 (5.6) and 47.7 (4.5) years, respectively, in the discovery set and discovery set and 46.8 (7.3) and 47.5 (6.1) years in the validation cohort. A majority of participants were non-Hispanic White (discovery set, 73.6%; validation set, 64.7%).

Among those with and without a FHBC in the discovery set, more from the FHBC group (11.1%) had a higher mean volumetric percent density to their breast tissue vs the non-FHBC group (9.0%). Further, after adjusting for age, body mass index, parity, race, age at menarche, and alcohol consumption, those with a FHBC had an overall 25% greater breast density vs the non-FHBC group (odds ratio [OR], 1.25; 95% CI, 1.12-1.41), and this remained high at 24% among those with at least 1 relative with a breast cancer history (OR, 1.24; 95% CI, 1.10-1.40). Among those who had at least 2 relatives with a breast cancer history, this rose even more to 40% (OR, 1.40; 95% CI, 0.95-2.07), but the authors deemed this difference “not significantly higher.”

Data from the validation cohort bear out similar findings, in that there was a higher likelihood of dense breasts among those with FHBC vs without, according to the BI-RADS scale: For those categorized as BI-RADS 3, 41.1% vs 38.8% were more likely to have dense breast tissue, and for those categorized as BI-RADS 4, 10.5% vs 7.7% were more likely to have dense breast tissue. Adjusting for the factors mentioned above again showed similar results, in that higher odds of dense breast tissue (BI-RADS 3-4) were seen among the FHBC vs the non-FHBC group: 30% overall (OR, 1.30; 95% CI, 1.17-1.45) and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) for the women with at least 1 relative with breast cancer. Odds among those with at least 2 relatives with breast cancer was higher still, at 38% (OR, 1.38; 95% CI, 0.85-2.23), but this again was deemed “not significantly higher” by the investigators.

All of the women in this study received their annual routine screening mammography at the Joanne Knight Breast Helath Center at Washington University School of Medicine and Siteman Cancer Center.

Noting that greater risk of breast cancer can come from several factors—chief among them being a first-degree relative with the disease, mammogram-identified dense breasts, premenopausal vs postmenopausal status, and women whose breasts are dense over more than 75%—the authors stress their findings are noteworthy because they were seen using both qualitative and quantitative measures.

In addition, women with a history of any cancer were not included in their data analysis. “Hence, our work provides new information about the associations between FHBC and mammographic breast density among premenopausal women,” they wrote.


Han Y, Moore JX, Colditz GA, Toriola AT. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. Published online February 17, 2022. doi:10.1001/jamanetworkopen.2021.48983

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