Mammogram reveals increased density (arrow) of the right breast. Image source: Indian J Radiol Imaging 2010 May;20(2):98–104.

Women with dense breasts and no lobular involution may face significantly higher risks of developing breast cancer, according to a study published in the Journal of the National Cancer Institute.

Previous studies have demonstrated that higher-density breasts and reduced lobular involution (age-related atrophy of breast lobules) are associated with higher risks of breast cancer. "Although lobular involution and MBD [mammographic breast density] are both associated with breast cancer risk, it is not known whether they represent independent risk factors for breast cancer," Karthik Ghosh, MD, of the Mayo Clinic in Rochester, Minn., and co-authors wrote.

The authors followed a sample of 2,666 female patients diagnosed with benign breast disease (BBD) for an average of 13.3 years. The study assessed the independent and combined association of breast density and lobular involution with breast cancer, classifying parenchymal pattern (MBD) in one of four categories ranging from nondense to extremely dense, and categorized lobular involution as either none, partial or complete.

Incidence of breast cancer in women with dense breasts and without lobular involution was measured at 507 per 100,000 person-years, while incidence of breast cancer in women with nondense breasts and complete involution was 247 per 100,000 person-years.

After adjusting for the effects of MBD and lobular involution, both characteristics were found to be independently associated with increased risks of cancer. Adjusting for a variety of factors associated with increased risk of breast cancer (including age or family history), as well as breast lobular involution, the hazard ratio for women with extremely dense (DY) breasts was 1.67, while the hazard ratio for women with ductal prominence occupying greater than 25 percent and less than 25 percent of the breast were 1.96 and 1.23 respectively (compared with the baseline hazard ratio of 1.0 for nondense breasts). The MBD-adjusted hazard ratios for women without lobular involution or with partial lobular involution were 2.62 and 1.61, respectively, with the hazard ratio for complete involution at 1.00.

"This study, to our knowledge, is the first to show that lobular involution and MBD are independently associated with breast cancer risk," the authors claimed.

In an editorial to the JNCI study, Gretchen L. Gierach, PhD, and co-authors from the National Cancer Institute in Bethesda, Md., acknowledged the importance of the findings of Ghosh and colleagues while restating and pointing out several limitations and areas for further study. Gierach noted the challenge of histologically identifying lobular involution, which is a biological atrophy that is difficult to view microscopically and is not well understood. Moreover, Gierach pointed out that the subjective assessment of breast density, a three-dimensional metric, using two-dimensional imaging brings inherent inaccuracies.

While not discounting Ghosh and co-authors' findings, Gierach and colleagues spoke of the importance of further studies and technological improvements to understand the intricate biological characteristics underlying breast density and lobular involution for predicting breast cancer, writing that such "factors may affect the performance of both involution and MBD as risk predictors."

An additional limitation mentioned by Ghosh and co-authors themselves was that their sample was overrepresentative of a white upper Midwestern population. The authors emphasized the importance of studying MBD and involution in more diverse samples of people.

"In conclusion," the authors affirmed, "we report that lobular involution and MBD are both risk factors for breast cancer, and that each provides unique information about breast cancer risk. These findings emphasize the potential for inclusion of these factors in future breast cancer risk prediction models."