This is important, Crandall said, because estrogens can increase the risk of uterine cancer and often are paired with progestin to prevent the malignancy in those who have not had a hysterectomy. So while the combination protects women from uterine cancer, it is increasing their risk of developing a breast cancer.

"These findings parallel what is known about breast cancer risk from the WHI. Breast cancer risk was elevated by combination estrogen and progestin therapy, but not by estrogen alone," Crandall said. "Now we know that new onset breast tenderness after combination therapy, but not estrogen alone, is associated with greater increases in breast density."

Using the WHI data, Crandall's team had previously shown in 2009 that women who experienced new onset breast tenderness after initiating combination hormone therapy had a 48% higher risk of subsequent breast cancer than women who did not experience new onset breast tenderness.

These new findings shed light on the biology that might partly explain the link between new onset breast tenderness and increased breast cancer risk during combination therapy, Crandall said. Understanding factors associated with mammographic density changes during therapy with estrogen and progestin may help give biological insights into hormone therapy-associated breast cancer risk.

"These findings emphasize the complexity inherent in the use of surrogate risk markers to assess menopausal hormone therapy-associated breast cancer risk," the study concludes.

Source: University of California - Los Angeles Health Sciences