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The WHI Findings on the Risk of Breast Cancer with Postmenopausal Hormone Therapy

The most frequent question women ask about postmenopausal hormone replacement therapy (HRT) is whether taking hormones (estrogen alone or estrogen plus progesterone) in one of the many available preparations will increase their risk of breast cancer.  For at least one of these preparations (conjugated equine estrogens plus medroxyprogesterone acetate, or Prempro™), the answer appears to be yes.   According to well-publicized data from the Women's Health Initiative (WHI) published in the Journal of the American Medical Association (JAMA, 6/25/03), HRT use for 5 years increased the overall risk of breast cancer by 24% and the specific risk of invasive breast cancer by 24% compared to women taking a placebo. 

What does this mean?  When the risk ratio from this study is multiplied out over 10,000 postmenopausal women, 8 more postmenopausal women who used HRT would have breast cancer per year than women who did not use HRT.  In contrast with previous studies of the relationship between breast cancer and HRT, the invasive breast cancers which occurred were significantly larger than those in women taking placebo and at a more advanced stage and were more likely to involve lymph nodes. This study also reported that HRT use was associated with a significant increase in the percentage of women with abnormal mammograms requiring additional medical evaluation.  

Does this mean that women who are currently taking HRT should stop or that women with menopausal symptoms should not take HRT?  No, it's not that clear cut.  It does mean that women who are currently taking HRT who have any concerns about this information should discuss it with their physicians.  As for women who are newly menopausal (or even perimenopausal) who have disruptive menopausal symptoms, these risks do not preclude taking HRT.  It is important to note that the women in the WHI had an average age of 63.2.  It is generally believed that the HRT-associated risk of breast cancer in younger women would be less and that HRT would offer them symptomatic relief. However, this is a highly individualized decision and risk-benefit analysis that should be carefully discussed between a woman and her healthcare provider. 

What about the issue of HRT making mammograms more difficult to interpret?  In general, informing your radiologist that you are taking HRT can help the interpretation.  Some physicians advise patients to discontinue HRT for 2 weeks prior to having their mammogram, which may help improve mammogram resolution in 75% of abnormal cases.  Digital mammography may also lesson this problem.  Again, whether or not this is necessary or helpful in your individual case should be discussed with your personal healthcare provider. 

This study is the final report of an earlier report released last year (7/02) when the National Institutes of Health chose to terminate this part of the WHI early because of these and other troublesome findings.  It is important to note that the part of the WHI study looking at women taking estrogen alone (Premarin™) is still ongoing and is expected to finish in 2005.  The bottom line?  Combined HRT should no longer be considered for preventive therapy in asymptomatic postmenopausal women.  It may be considered for the treatment of menopausal symptoms in younger menopausal women for 5 years or less so long as they have no contraindications. 

Created: 9/3/2003  -  Donnica Moore, M.D.

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