SAN ANTONIO — While endogenous estrogen (i.e., estrogen produced by ovaries and by other tissues) does have a well-known carcinogenic impact, hormone replacement therapy (HRT) utilizing estrogen alone (the exogenous estrogen) provides a protective effect in reducing breast cancer risk, according to study results presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 8-12.
“Our analysis suggests that, contrary to previous thinking, there is substantial value in bringing HRT with estrogen alone to the guidelines. The data show that for selected women it is not only safe, but potentially beneficial for breast cancer, as well as for many other aspects of women’s health,” said lead researcher Joseph Ragaz, M.D., medical oncologist and clinical professor in the faculty of medicine, School of Population and Public Health at The University of British Columbia, Vancouver, BC, Canada.
“These findings should intensify new research into its role as a protective agent against breast cancer,” he added.
Ragaz and colleagues reviewed and reanalyzed data from the Women’s Health Initiative (WHI) hormone replacement therapy trials. WHI is a national health study that focuses on strategies for preventing heart disease, breast and colorectal cancer, and fracture in postmenopausal women. The WHI was launched in 1991 and includes more than 161,000 U.S. women aged 50 to 79 years.
“Over the last 30 years HRT has been used almost indiscriminately by women expecting the benefit of reducing cardiac risks, while providing a protective effect against bone fracture, and improving overall quality of life,” said Ragaz. “The WHI results as originally interpreted led to a major pendulum swing against HRT.”
The WHI HRT trial consisted of two cohorts of women; the estrogen-alone group of women without a uterus and the estrogen-plus-progestin group of women with a uterus.
Ragaz and colleagues reanalyzed the WHI studies in more detail and found that subsets of women with no strong family history of breast cancer who received estrogen alone had a significantly reduced breast cancer incidence. In addition, the 75 percent of women without benign disease prior to the trial enrollment also had a reduced breast cancer risk.
“Reduction of rates of breast cancer in the majority of women who are candidates for estrogen-based HRT is a new finding because estrogen was always linked with a higher incidence of breast cancer,” Ragaz said, “yet estrogen administered exogenously is actually protective for most women.”
Based on the results of this current analysis, Ragaz suggested that “while the use of HRT with estrogen alone may reduce the risk of breast cancer and may also be appropriate to manage menopausal symptoms, further research is warranted to elaborate on the optimum treatment regimen, to refine the selection of ideal candidates for estrogen therapy, and to understand the estrogen mechanisms that support the prevention of human breast cancer.”
“The recommendations based on prior analyses of the results of the WHI HRT studies was not to use HRT, but we are optimistic this will change,” he said. “Our conclusion, based on the data presented, should enhance considerations for an early approval of HRT based on estrogen-alone for the majority of selected women suffering with menopausal symptoms and galvanize new research on HRT to define the optimum regimens for individual women.”
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The mission of the CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for breast cancer patients. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor, and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. The 33rd annual symposium is expected to draw nearly 9,000 participants from more than 90 countries.
This is wishful thinking and dangerous advice! Dr. Ragaz is really stretching these data to paint a favorable picture of estrogen therapy. He is absolutely correct in his assertion that estrogen alone in the WHI led to a non-significant 20% decrease in breast cancer risk in women with hysterectomy. However, this was not the only finding – additional analyses showed 1. taking estrogen led to more screening mammograms and additional biopsies 2. the hormone caused an increase in the rate of benign proliferative breast disease (lumps that are a harbinger of future risk and 3. estrogen led to larger tumors that were more likely to be lymph node positive (35% vs. 23%).
What this analysis did not address was that the WHI estrogen alone trial actually mirrored several longer observational studies, specifically the Nurses’ Health Study and the California Teachers’ Study, which showed no increase in breast cancer when estrogen alone was used for less than 10 years (like WHI there were non-significant decreases). However, increased risk was found when estrogen was used for more than 15 years. One interesting point Dr. Ragaz makes is that estrogen THERAPY (usually Premarin) may have weaker effects on a woman’s breast than her own estrogen. This seems plausible, given that European observational studies (namely E3N and the Million Women Study) on mostly estradiol-based HRT (the “bioidentical” kind) have shown significant increases in breast cancer with the use of estrogen alone for 8-10 years.
While thiese data are not conclusive, it is irresponsible of Dr. Ragaz to suggest using estrogen alone to prevent anything. Despite his suggestion of a favorable effect of estrogen alone, the hard data from WHI say otherwise. Estrogen used alone has no significant age-specific effect on the risk of heart disease and there is no net benefit or risk for younger vs. older women. However, stroke and blood clots are increased, whether the woman is in her 50s or her 70s. Also, these risks emerge immediately within one year after women begin estrogen therapy, making the drug unsuitable for disease prevention.