A new study showed that taking menopausal hormone therapy comprising estrogen plus progestin for five years doubled a woman’s risk of breast cancer, and suggested that the recent fall in breast cancer rates is predominantly due to a decrease in women having combined menopausal hormone therapy.
The study was the work of lead investigator Dr. Rowan Chlebowski of Harbor-UCLA Medical Center in Los Angeles, and colleagues, and was presented on Saturday 13 December at the San Antonio Breast Cancer Symposium.
When the results of the Women’s Health Initiative (WHI) trial investigating the effects of estrogen plus progestin were reported in JAMA in 2002, use of hormone therapy for treating menopause symptoms went down dramatically in the United States. This was followed by a substantial fall in breast cancer incidence, which according to a study published in NEJM in 2007, may have been linked to the fall in hormone therapy use. However, the debate about whether the link was causal has been somewhat inconclusive.
For this study, Chlebowski and colleagues re-analyzed the data on the two parts of the WHI trial.
The first part of the WHI trial was a randomized trial where over 16,500 women took daily doses of conjugated equine estrogens (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) or placebo. This trial was stopped when researchers observed a 26 per cent higher risk of breast cancer among the women on the hormone combination. But this result was an average over the 5.5 years of the trial.
So Chlebowski and colleagues re-analyzed the data differently – they looked at how the breast cancer cases arose over the period of the trial and found that for 15,387 of the women the risk started going up when they started on the hormones, rose gradually as they continued, then peaked when they stopped, and went down again as the women stopped the therapy.
Analyzing the data this way showed that the risk of breast cancer for the women on the hormone therapy at the peak was twice that for the women on placebo.
The second part of the WHI trial was an observational study of just over 16,000 women who had already been taking hormone therapy for menopause symptoms for an average of seven years and comparing them with a group of over 25,000 women who had never taken hormone therapy. This part of the trial has not reported breast cancer results yet.
Again, by looking at incidence over time, Chlebowski and colleagues noticed that the women on hormone therapy started with double the risk of the non-users and that risk went down as women came off the therapy. The year after the news about the link between hormone therapy and breast cancer broke, in this study the number of women on hormone therapy dropped to just over 40 per cent of the number that started out.
For both parts of the study, the researchers ruled out frequency of mammograms as a factor.
The researchers concluded that:
“These findings suggest that cessation of E+P [estrogen plus progestin] use is associated with a rapid reduction in breast cancer incidence which is not explained by mammography utilization change and support the hypothesis that the recent reduction in breast cancer incidence seen in certain age groups is predominantly related to a decrease in combined menopausal therapy use.”
Chlebowski and colleagues found that even taking the hormone therapy for two years significantly increased a woman’s risk of breast cancer, but when she stopped taking it the risk rapidly diminished and only two years after stopping returned to the level it was at before she started.
Dr. Claudine Isaacs of Georgetown University’s Lombardi Comprehensive Cancer Center told the Associated Press that this was an “excellent message for women” because even if you have been on the hormones for a long time you can still bring the risk down:
“It’s not like smoking where you have to wait 10 or 15 years for the risk to come down.”
The WHI trial stopped when the early findings showed the increased risk of breast cancer and cardiovascular symptoms among the women taking the combined hormone therapy. The message that went out was don’t stay on hormone therapy for a long time and only use if for short term use of severe symptoms, and use lower doses.
But Chlebowski told the Associated Press that this study questions whether women should start treatment at all.
The debate that is now opened by this study is whether hormone therapy is likely to remain a clinically viable option for women whose symptoms are severe, in those cases where the risks of short term use at low dosage is considered to be reasonable compared to the relief that the therapy brings, especially in the knowledge that those risks go away faster than previously thought.
“Breast cancer after stopping estrogen plus progestin in postmenopausal women in the womens health initiative.”
Chlebowski RT, Kuller L, Anderson G, Mason JA, Schenken R, Rajkovic A, Stefanick M, Sarto G, Ravdin P.
Presented at San Antonio Breast Cancer Symposium, Saturday 13 December 2008.
Abstract No 64, General Session 6
Click here for San Antonio Breast Cancer Symposium.
Sources: San Antonio Breast Cancer Symposium, Associated Press.
Written by: Catharine Paddock, PhD