Hormone therapy associated with increased risk of death from breast cancer

UB to manage $8.2 million to fund new round of WHI studies

Results of a new Women's Health Initiative (WHI) report show that hormone therapy is associated with an increased the risk of death from breast cancer, as well as an increased risk of developing invasive breast cancer in postmenopausal women.

Jean Wactawski-Wende, PhD, professor of social and preventive medicine at the University at Buffalo and one of the primary authors on the paper, published today in JAMA, says the breast cancers found in these women also tended to have more lymph node involvement, indicating a poorer prognosis.

"This report, which expands on earlier results of the WHI study, followed these women for an average of 11 years," says Wactawski-Wende. "The data show that, with further follow-up, there remains an increased incidence of breast cancer in women taking estrogen plus progestin.

"In fact, women taking estrogen plus progestin are more likely to die from breast cancer and from other causes than women who did not take these hormones."

The paper was posted online Oct. 19 at http://jama.ama-assn.org/cgi/reprint/304/15/1684.

Wactawski-Wende was co-PI at UB's WHI Vanguard Center, one of 16 that helped develop the initial protocols for the study, which began in 1993 and eventually included 40 clinical centers across the U.S. Initially planned to continue until 2005, the hormone trial was halted in 2002 because preliminary analysis of the data showed estrogen plus progestin increased the risk of heart disease, stroke and invasive breast cancer. Prior to WHI, scientists speculated that hormone therapy reduced heart disease risk.

The WHI continued to follow these women after the main trial ended. The current JAMA paper reports the results of research conducted during this WHI extension phase. Most of the earlier observational studies, which follow participants over time and collect health information at specific intervals, had suggested that breast cancers that develop in women taking hormone therapy were less advanced and had a lower risk of death.

However, the WHI researchers note in the JAMA paper that the influence of estrogen plus progestin on breast cancer mortality had not been addressed in the context of a randomized clinical trial, prior to WHI.

Their current study to answer that question was based on 12,788 surviving postmenopausal women who took part in the initial trial.

Results showed that combined hormone therapy increases the incidence of invasive breast cancer and that, more commonly, the cancers had spread to the lymph nodes. There also were more deaths attributed to breast cancer in those taking hormone therapy -- 2.6 versus 1.3 per 10,000 women. There also were more deaths from all causes in the women who had been diagnosed with breast cancer who were on hormone therapy -- 5.3 versus 3.4 per 10,000.

The trial also found that hormone therapy interfered with detection of breast cancer, leading to cancers being diagnosed at a more advanced stage.

"These findings related to increased mortality in estrogen plus progestin users were surprising," says Wactawski-Wende. "Prior studies had suggested that, although these women were diagnosed with breast cancer, their prognosis was more positive than those who were not on hormone therapy when diagnosed. This study emphasizes the importance of clinical trial data to understand the risks and benefits of taking hormone therapy."

Wactawski-Wende will oversee the next five-year round of WHI studies carried out by the nine original WHI research centers in the Northeast, funded by an $8.2 million award to UB from the National Heart, Lung and Blood Institute. Rowan T. Chlebowski, MD, PhD, from Harbor-UCLA Medical Center, is principal author on this report.