Estrogen May Help Lower Risk of Breast Cancer in Some Women

Women who received estrogen while part of the Women's Health Initiative (WHI) trial had lower rates of invasive breast cancer compared to those who received placebo, and they were less likely to die of the disease compared to women who never took the hormone replacement therapy. Premarin, a conjugated mare estrogen was used in the study and is the main conjugated estrogen prescribed in the United States.

Premarin structure

The long-term follow-up analysis is published in the Lancet Oncology, validating the original observation that breast cancer risk is lower in postmenopausal women who have had a hysterectomy. Women took estrogen for a median of 5.9 years.

The findings provide some reassurance for women who have had a hysterectomy and are seeking relief from postmenopausal symptoms, according to the study's lead author, Garnet L. Anderson, PhD, a researcher at the Fred Hutchinson Cancer Research Center in Seattle, Washington.

After a median of 11.8 years of follow-up, estrogen was associated with a 23% reduction in invasive breast cancer compared to placebo (P = .02). Absolute risk, however is relatively small-0.27% per year for women taking estrogen compared to 0.35% for women taking placebo. Women that did develop breast cancer and who took estrogen were less likely to die of the disease. The estrogen group had a 63% reduction in death compared with the placebo group (6 deaths compared to 16, P = .03).

Women who appeared to benefit the most did not have benign disease or a family history of breast cancer. Over 10,000 women aged 50 to 79 were enrolled in the US-based, randomized, placebo-controlled study and 7,645 were followed long term from March 2005 until August 2009. The median follow-up after treatment was stopped was 4.7 years. All women had had a hysterectomy and an expected 3-year survival.

The WHI trial was started in 1993 to investigate the effect of conjugated equine estrogen on chronic disease. The trial was stopped one year early, in 2004, due to an increased stroke signal and increase in blood clots. Therefore, the data do not support the use of estrogen for breast cancer risk reduction.

Part of the WHI trial aimed to test the efficacy of taking estrogen and progestin, but this portion of the study was stopped early after an interim analysis showed an increased link of breast cancer in the experimental arm. Based on the new results published last week, the breast cancer risk profile of women with a prior hysterectomy taking estrogen are different from women taking estrogen in combination with progestin.

"Our data do not support the use of estrogen for breast cancer risk reduction in light of the lack of benefit noted in populations at higher risk (including those with a strong family history of breast cancer or benign breast disease) and the additional risk of stroke and blood clots," the authors state.

In an accompanying editorial, Anthony Howell from the University Hospital of South Manchester, UK, and Jack Cuzick from Queen Mary, University of London stress that while the results provide insight into the value of hormone replacement therapy, women should be counseled about the small increases in thromboembolism that is linked to taking these hormones.

It is not yet clear why estrogen can lower breast cancer risk in women who have had a hysterectomy. The mechanism of how mammary cells respond to estrogen is still also being teased out. In vitro, mammary cells are able to adapt to low estrogen levels, first ceasing to grow and subsequently adapting after several months, explains Howell. The phenomenon is called adaption, and goes the other way-the cells adapt to higher estrogen levels as well. Unfortunately, it is not well understood.

"The importance [of this study], in addition to the reduction in breast cancer risk, is that women who do have the misfortune of developing breast cancer have a reduced death rate if the cancer develops while on Premarin," says Howell.