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(Reuters Health) - Seven years of treatment with conjugated equine estrogen (CEE) in postmenopausal women with prior hysterectomy does not raise the risk of breast cancer, and may in fact reduce the risk, according to a detailed analysis of data from the Women's Health Initiative (WHI) Estrogen-Alone trial.

The WHI revealed that women treated with estrogen plus progestin had a higher incidence of invasive breast cancers diagnosed at more advanced stages, Dr. Marcia L. Stefanick and her associates note in their report, published in the Journal of the American Medical Association for April 12.

However, preliminary examination of the WHI Estrogen-Alone trial found fewer breast cancers among subjects in the CEE arm of the study. The research team therefore more closely analyzed data from the 10,739 postmenopausal women with prior hysterectomy, who were 50 to 79 years of age when enrolled between 1993 and 1998.

The subjects were randomly assigned to 0.625 mg/d of CEE (Premarin) or placebo. During an average follow-up of 7.1 years, 237 cases of invasive breast cancer and 55 in situ cancers were diagnosed.

Dr. Stefanick, from Stanford University in California, and her group observed nonsignificant reductions in invasive breast cancer (hazard ratio 0.80) and for total breast cancer (HR 0.82) associated with CEE use.

However, 54% of subjects were no longer adherent to study medication at the end of follow-up. After adjusting for adherence in which follow-up was censored 6 months after treatment discontinuation, there was a larger and significant reduction in the incidence of invasive breast cancer in the CEE group (HR = 0.67, p = 0.03).

CEE appeared to exert a protective effect in women with a lower 5-year Gail Risk Score (p = 0.01), benign breast disease (p = 0.005), and those with no first-degree relatives with breast cancer (p = 0.01).

"Such findings suggest a stronger influence of CEE on breast cancer not linked to family history and/or those less likely to be associated with microcalcification, a mammography finding that often leads to recommendation for breast biopsy," Dr. Stefanick's team notes.

More women in the CEE group had mammograms with abnormalities requiring short-term follow-up (36.2% versus 28.1%, p < 0.001), a disadvantage in terms of emotional and economic costs associated with repeat mammography screening after 6 months.

Dr. Stefanick and her colleagues conclude: "Initiation of CEE alone in women after hysterectomy should continue to be based on careful consideration of potential risk and benefits for a given individual."

JAMA 2006;295:1647-1657. [link to:]

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