HRT Linked to High Risk of Breast Cancer Recurrence

HRT Linked to High Risk of Breast Cancer Recurrence

Feb. 2, 2004 — Women with a history of breast cancer are at significantly higher risk of recurrence when using hormone replacement therapy (HRT) for menopausal symptoms, according to the results of a randomized trial published in the Feb. 7 issue of The Lancet and posted online Feb. 3. The "Hormonal replacement therapy after breast cancer diagnosis — is it safe?" (HABITS) trial was stopped short when interim analysis showed increased risks of breast cancer recurrence for HRT users.

"The HABITS trial was terminated because women with a history of breast cancer allocated to receive HRT for menopausal symptoms experienced an unacceptably high risk of breast cancer compared with breast-cancer survivors allocated to best symptomatic treatment without hormones," lead investigator Lars Holmberg, from University Hospital in Uppsala, Sweden, says in a news release. "Women on active treatment have been advised to discontinue."

The HABITS trial was one of several trials begun in the 1990s to evaluate the potential risk of recurrent breast cancer in women using HRT. Although it was designed to enroll at least 1,300 women and to follow them for five years, it was stopped on Dec. 17, 2003, after a median follow-up of slightly longer than two years. All subjects had previous breast cancer and were randomized to receive HRT or no HRT with at least one follow-up evaluation.

Of 434 women enrolled as of September 2003, 345 had at least one follow-up report, with a median follow-up of 2.1 years. Recurrent or de novo breast cancer had developed in 26 women in the HRT group and in seven women in the no-HRT group. All women with a breast cancer event in the HRT group and two of those assigned to the no-HRT group had received HRT, and most had their breast cancer event while receiving treatment.

"The women in the trial will be followed up for many years and the steering committee of the HABITS trial will continue to collaborate with other ongoing studies in the same clinical domain," Dr. Holmberg says.

Novo Nordisk funded the data management for this study, and the Nordic Cancer Union and the Swedish Cancer Society helped support it.

In an accompanying commentary, Rowan T. Chlebowski, from the Harbor-UCLA Research and Education Institute, and Nananda Col, from Brigham and Women's Health Hospital in Boston, Massachusetts, note the strengths of the HABITS trial and suggest that it is the "last word" on the use of HRT in women with breast cancer.

"Considering all available evidence about the effect of hormone therapy on breast cancer and chronic disease, the HABITS investigators' conclusion that even short-term use of hormone therapy poses an unacceptably high risk of breast cancer can now reasonably guide clinical practice for women with breast cancer," they write. "Alternative safe and effective strategies for the difficult problem of menopausal symptoms in these women now need to be developed."

Dr. Chlebowski reports receiving honoraria from AstraZeneca, Novartis, and Lilly, and he is an investigator in the Women's Health Initiative. Dr. Col reports no financial conflicts of interest.

In a statement from the American Cancer Society, Chief Medical Officer Harmon J. Eyre, MD, said that the study " is large enough and clear enough to show that HRT appears to increase the chance of a new or recurring breast cancer. Because of that, offering HRT to women with a history of breast cancer would be unwise."

Laurie Barclay, MD

Lancet. 2004;363:453-455