Hormonal therapy and cancer risks

Marc Espie
Breast Disease Center, Medical Oncology, Hôpital Saint-Louis, Paris, France

The Women’s Health Initiative (WHI) study is the first large-scale randomized trial concerning postmenopausal hormone therapy. The participants are from North America where their epidemiological data and their breast cancer incidence are higher than, for example, in France. Thus, this study cannot be extrapolated as such to our context in France.

The study confirms previous data concerning hormone therapy and the incidence of cancers. A small excess of breast cancers, a decrease in colon cancers and a neutral effect on endometrial cancers have been observed.

A number of randomized studies (Hormone Estrogen/progestin Replacement Study (HERS), Postmenopausal Estrogen/Progestin Interventions (PEPI), Women's Estrogen for Stroke Trial (WEST), and the Nachtigall study) had been published before the WHI study. None of them revealed a statistically significant elevation in the risk of breast cancer, but they were concerned with specific catagories of women, often with a cardiovascular disease, and they were not important enough in terms of numbers and follow-up time for a statistically significant difference to appear.

A total of 16 608 postmenopausal women aged 50–79 years were enrolled in the WHI study. The median follow-up time was 5.2 years. The women were randomized between a placebo and a combination of medroxyprogesterone acetate and conjugated equine estrogens. Of the participants, 26% had previously been given hormone therapy.

In the patients on hormone therapy, 166 breast cancers were reported compared with 124 cases in the placebo group. Increased risk was only observed in prior users of hormone therapy. No excess of cases of breast cancer in situ were noted. As regards endometrial cancer, no elevation was noted, with a hazard ratio of 0.83 (CI, 0.47–1.47) and, for colon cancers, a decrease was reported (hazard ratio, 0.63 (CI, 0.43–0.92)). In total, an overall analysis of all the cancers observed did not reveal any statistically significant elevation.

Since these findings were published, fresh research has been conducted in the form of meta-analyses of meta-analyses or of meta-analyses of randomized trials. Overall, no elevation in mortality from cancer was found and the same magnitude of results as in the WHI study was observed regarding cancer incidence.

Hormone therapy probably has a promoter effect on pre-existent infraclinical breast cancers. This combination of estrogens plus progestin is not commonly used in France, so extrapolation to our therapies is difficult. The role of progestins can be questioned, as the WHI study concerning estrogens used alone in hysterectomized women is concurrently being continued and no elevation has been observed after 5 years.