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Hormone Therapy and Breast Cancer Risk

The exact effect of hormone replacement therapy on breast cancer risk has still not been definitively established. No, not even the large studies including the Women’s Health Initiative (WHI - US) and the Million Women Study (MWS - UK) were able to do that. The general feeling is that the use of exogenous estrogen (especially in conjunction with a progestin) increases the risk of breast cancer beyond 5 years of use. However, the estrogen-only arm of WHI actually showed a reduction in breast cancer in women who were compliant with their Premarin therapy!

After detailed and meticulous review of the literature, I believe the legitimate conclusion at this time is that Estrogen does NOT initiate or cause breast cancer. Estrogen can be looked upon more accurately as a “fertilizer” that accelerates the growth of preexisting breast cancer cells. This “fertilizer effect” actually leads to a detection bias – by making the breast cancer cells proliferate faster, it becomes more readily detectable (by mammogram or palpation) at an earlier stage. In fact, there is evidence that women who are diagnosed of breast cancer while on hormone therapy have a better prognosis (less aggressive cancer, lower mortality) than women who are diagnosed of breast cancer who have not been on hormone therapy!

Recently in December 2006, a press release from MD Anderson Cancer Center indicated a drop in breast cancer rate in 2003, the year after the “bomb dropped” – when Prempro arm of WHI was stopped in 2002. Many people interpreted this finding as support for estrogen causing breast cancer, but I will tell you why I (and many other experts in menopause) feel that this is an erroneous view. While it is true that many women were scared by all the negative publicity surrounding WHI and discontinued hormone therapy. But the drop in breast cancer rate happened much too quickly to be in keeping with the theory that estrogen causes breast cancer – the process for a cancer to develop from nothing to a few cells and eventually to about 1cm when it is clinically detectable takes about 10 years. It would be biologically implausible for the cancer rate to drop after a year of reduced estrogen use! In fact, the finding of reduced breast cancer incidence in 2003 is much more in keeping with the “estrogen as fertilizer” theory – that estrogen increases growth of preexisting cancer cells – and the removal of this “fertilizer” slowed down the growth of preexisting cancers and made the difference between detectable or not by mammogram. An important factor that most likely contributed to the observed decline in breast cancer incidence was the drop in mammogram rates in 2003. Many women who discontinued hormone therapy may have mistakenly thought that they no longer needed to be as vigilant about getting mammograms. Some women may have been avoiding physician contact for fear their doctors may not have been in agreement with their decision regarding hormone therapy (This can be true for both women who decided to stop their own hormones, and for those who decided to continue hormones despite some physicians’ opposition). Other factors that may have contributed to the reduction in breast cancer include increases calcium and vitamin D supplementation (Vitamin D may reduce risk of breast cancer) and increased use of Evista (a medication for osteoporosis) that has been found to be associated with reduced breast cancer risk in the years prior to 2003.

Even if we believe that the study evidence so far showing a small increase in breast cancer risk is valid, it is important to put this magnitude of risk into perspective. The increased risk of diagnosis of breast cancer with HRT is similar to the risk incurred by nulliparity (never having had children), late first pregnancy (age > 35), early menarche (first menstrual period before age 11), and moderate alcohol consumption (>20grams/d). Actually, the risk of breast cancer is increased by obesity to a significantly higher extent than by HRT!! So let’s concentrate our efforts in a healthy lifestyle with nutrition and exercise, and spend less energy in arguing about the risk of HRT!!