A recent study found a significantly higher risk of developing breast cancer in women who developed new-onset breast tenderness after initiating estrogen-plus-progestin hormone replacement therapy.1

The research was based on data from more than 16,000 women participating in the Women's Health Initiative estrogen-plusprogestin clinical trial, which was stopped in July 2002 when researchers found an elevated risk of developing invasive breast cancer among women receiving estrogenplus-progestin combination therapy.

Lead researcher Carolyn Crandall, MD, says that she and colleagues do not know why breast tenderness indicates an increased cancer risk for these women. Dr. Crandall is a clinical professor of general internal medicine and health services research at the David Geffen School of Medicine at the University of California at Los Angeles. One possible theory is that hormone replacement therapy causes breast tissue cells to multiply more rapidly, which causes breast tenderness while also increasing cancer risk, she says.

In the trial, 8506 women received therapy with estrogen plus progestin, and 8102 were given placebos.Women receiving the combination therapy who did not have breast tenderness at the beginning of the trial had a 3-fold greater risk of developing tenderness after 1 year compared with those who were given placebos (36.1% vs 11.8%).

The women in the combination therapy group who developed breast tenderness after a year also had a 48% higher risk of invasive breast cancer than those receiving combination therapy who had not experienced tenderness by the first-year follow-up visit.

Dr. Crandall says she does not know of other published studies that have addressed an association between conjugated equine estrogens plus medroxyprogesterone acetate-induced, new-onset breast tenderness and breast cancer risk.


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  • 1
    Crandall CJ, Aragaki AK, Chlebowski RT. et al. New-onset breast tenderness after initiation of estrogen plus progestin therapy and breast cancer risk. Arch Intern Med. 2009; 169: 1684-1691.