Homing in on mechanisms linking breast density to breast cancer risk.

I n probably the best-known finding from the Women’s Health Initiative, postmenopausal hormone therapy with estrogen and progestin was linked to a substantial increase in breast cancer risk. Now researchers think that the increase may be explained by an associated rise in breast density. Among women taking hormone therapy in the large, prospective women’s health study, both the density found on baseline mammograms and the change in density were statistically signifi cantly associated with breast cancer risk, according to Celia Byrne, Ph.D., assistant professor at Georgetown University’s Lombardi Comprehensive Cancer Center. Byrne discussed the results of this new analysis of Women’s Health Initiative data at the 2010 American Association of Cancer Research meeting in April. Researchers now consider mammographic density — the amount of white, radiodense area compared with the amount of gray, radiolucent area on a mammogram — one of the strongest independent risk factors for breast cancer ( see “Breast Density Gains Acceptance as Breast Cancer Risk Factor,” J. Natl. Cancer Inst. 2010;102:374 – 5). But researchers do not fully understand just how breast density increases breast cancer risk. Research into the biological mechanisms underlying breast density and linking it to breast cancer risk has been an understudied area, according to Paolo Provenzano, Ph.D. , a research associate at Seattle’s Fred Hutchinson Cancer Research Center. That situation is changing as Provenzano and others have begun to identify some of the complex biological processes that account for breast density and to explain how they affect breast tissue. “Direct studies to begin to address a causal relationship between breast tissue density and cancer have only started to emerge,” Provenzano said. “While there is still much work to be done, I believe that high breast tissue density is causal for the increasing risk of developing breast cancer.”