Of the women who reported new-onset breast tenderness, 76.3 percent had been on the combination therapy.

Women in the combination therapy group who did not have breast tenderness at the outset but experienced new-onset tenderness at the first annual follow-up had a 48 percent higher risk of invasive breast cancer than their counterparts on combination therapy who did not have breast tenderness at the first-year follow-up.

"To our knowledge, no prior published studies have addressed whether there is an association between CEE+MPA-induced new-onset breast tenderness and breast cancer risk," Crandall said.

The study does have limitations. The data the researchers used assessed breast tenderness only annually and thus could have underestimated it. Also, the rates of women discontinuing the combination therapy and switching from placebos to active therapy were relatively high, though the researchers believe this could have decreased, rather than increased, the observed association between new-onset tenderness and cancer risk. And the results don't apply to other types of estrogen or progestin therapy.

Source: University of California - Los Angeles