Although several studies have demonstrated an increased risk of breast cancer in post-menopausal women taking oral hormone therapy, the risk related to each of the various forms of therapy is less clear. The Million Women Study collaborators report on the incidence of breast cancer and mortality related to different forms of hormone therapy.

Researchers used data from the National Health Service Breast Screening Programme, which offers mammographic screening every three years to all British women 50 to 64 years of age. Between May 1996 and March 2001, the invitation for screening included a questionnaire about sociodemographic and other factors, menstrual and gynecologic history, and use of hormone therapy. The medical records of study participants were traced on national cancer and death registries.

Investigators followed 1,084,110 women (average age at recruitment, 55.9 years) who had no history of any form of cancer before study entry. One half of the women had used hormone therapy at some time. Participants were followed for an average of 2.6 years for breast cancer development and 4.1 years for causes of death. During the study, 9,364 invasive breast cancers were detected, and 637 women died of breast cancer.

Among the 828,923 postmenopausal women in the study, the risk of breast cancer was significantly higher in women who had used hormone therapy (relative risk, 1.43). Risk was further increased in women who were currently using hormone therapy (relative risk, 1.66). Among current users, the highest risk of developing breast cancer was associated with combined estrogen-progestin preparations. This risk was significantly higher than that for users of other preparations. For each hormone therapy regimen, the risk of developing breast cancer was further increased by the duration of use. Risk was lowest in women using transdermal preparations, followed by oral and implanted formulations.

The authors estimate that 10 years’ use of estrogen-only therapy results in three to seven additional breast cancers per 1,000 women treated; in women using combination therapy, 18 to 20 additional breast cancers per 1,000 women will develop. Reliable estimates of the effect of hormone therapy on breast cancer deaths cannot yet be established. The authors call for further studies to clarify the risks for different subgroups of hormone therapy users and to establish the effect of therapy on breast cancer mortality.

editor’s note: The focus of the hormone therapy controversy now seems to be shifting from heart disease to breast cancer. The danger is that a blanket approach of “all hormone therapy is bad” obscures the benefits of hormone replacement in selected patients, especially for relief of vasomotor symptoms and prevention of osteoporosis. Much depends on how the statistics are reported and applied. Every woman has her own combination of factors and risks, but our current knowledge only permits gross generalizations. In this study, consideration of only three variables (age, type of therapy, and duration of use) shows that younger women using estrogen alone are at no increased risk, and that even 10 years of estrogen alone is associated with only three to seven additional cancers per 1,000 women. These rates may be further influenced by route of administration (especially transdermal). As family physicians, we must apply the cautions and statistics to individual women. We must ascertain individual vulnerabilities to breast cancer, heart disease, gynecologic cancers, osteoporosis, and multiple other conditions, and advise our patients accordingly. Above all, we must do two things: involve the patients in the decisions and remain vigilant, monitoring the research evidence as it unfolds and continually adjusting the care of our patients accordingly. Patients should make important health care decisions based on their physician’s advice, not on news stories.—A.D.W.