BCRF researcher and team investigate two strong breast cancer risk factors in premenopausal women

We know that breast cancer risk is elevated in women who have a family history of breast cancer and those with dense breasts, but few studies have examined whether these strong risk factors are associated.

A new BCRF-supported study has addressed this question and provided new insights—particularly for premenopausal women.

Breast cancer risk, family history, and breast density

Researchers have long recognized that understanding the factors that increase an individual’s risk for breast cancer is key to personalizing risk prediction and prevention.

Studies have found that women with a family history of breast cancer (in a close relative such as a parent or sibling) have a two to four times greater risk of the disease themselves.

Breast density—the ratio of connective and glandular tissue to fatty tissue—is also associated with an increased risk; women with more than 75 percent dense breast area have a four-to-six-fold increase in breast cancer risk compared to women with less than five percent dense area (mostly fatty tissue).

This increased risk is due, in part, to the difficulty in detecting suspicious lesions that may be masked by dense tissue and missed by mammograms. Studies have also shown that the genes associated with having dense breasts are the same as those for developing breast cancer, suggesting that the increased risk of breast cancer in women with dense breasts is multi-factorial.

Designing a study to tackle two big questions

In this study, BCRF investigator Dr. Graham Colditz and his colleagues tested the hypothesis that a family history of breast cancer is associated with a higher risk of having dense breasts and focused on premenopausal women. Menopausal status was a particularly important aspect of the study since breast density decreases with age due to hormone changes that occur during menopause, and premenopausal women tend to have denser breasts than postmenopausal women.

“These two factors have strong associations with breast cancer risk but surprisingly, there is limited data on how they are both related—especially in premenopausal women and African American women,” Dr. Colditz said.

The team’s study provided several advantages over prior reports. The dataset contained over 14,000 premenopausal women to statistically improve interpretation of the results, and the study population was racially diverse, reflecting the population distribution in the greater St. Louis–area where the study took place. Additionally, researchers used two methods of measuring breast density (volumetric and mammographic) to confirm that results were consistent and independent of the method. In fact, this study was the first to assess the connection between family history and breast density using volumetric methods—those that provide a more objective assessment of breast tissue volume by using artificial intelligence and mathematical modeling to digitally analyze mammograms.

Results and implications

Dr. Colditz and his team demonstrated that their hypothesis was correct: In premenopausal women, having a family history of breast cancer was, in fact, associated with having dense breasts. Both Black and white women showed similar results. Furthermore, a strong and consistent association was found regardless of whether breast density was measured by qualitative (mammographic) or quantitative (volumetric) means.

These results highlight the importance of knowing your family history and, for premenopausal women with a family history, talking with your doctor about starting breast cancer screening at an earlier age to detect the disease sooner.

And, pulling back the lens, these results also underscore the greater need to move toward more personalized risk-based screening that is tailored to each person’s risk rather than age. 

“Our study strongly reinforces the message that women who have a family history of breast cancer, irrespective of race, should start annual screening mammogram early,” Dr. Colditz said. “And we are still exploring ways to build on these findings but certainly want to better understand how this can help us work toward better prevention approaches for premenopausal breast cancer."

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