Estrogen Benefit in Breast Cancer Affirmed

Reduced breast cancer risk with use of estrogen-only hormone therapy after hysterectomy persists long term, researchers affirmed in an analysis of the Women’s Health Initiative (WHI) trial.

Women who used estrogen for a median of six years had a 23% lower invasive breast cancer over a median of almost 12 years of follow-up (0.27% versus 0.35% per year with placebo, P=0.02), reported Garnet L. Anderson, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues in Lancet Oncology online.

That benefit was concentrated largely among low-risk groups, such as those without benign breast disease or a family history of breast cancer.

“Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms,” the group wrote. “However, our data do not support use of estrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.”

Unlike some other trials of unopposed postmenopausal estrogen therapy, the estrogen-only portion of WHI had suggested a preventive effect, which persisted into the first analysis of the long-term phase of follow-up at a median of 10.7 years.

That raises important questions about the disparity between studies, Anthony Howell, MD, of the University Hospital of South Manchester, England, and Jack Cuzick, PhD, of Queen Mary University of London, noted in an accompanying commentary.

Estrogen & Breast Cancer Risk: Factors of Exposure
Estrogen is a hormone that is necessary for the normal development and growth of the breasts and organs important for childbearing. It helps control a woman’s menstrual cycles and is essential for reproduction. Estrogen also helps maintain the heart and healthy bones. However, a woman’s risk for breast cancer is associated with lifetime exposure to estrogen. Understanding how estrogen works in the body, knowing about how chemicals in the environment can affect body estrogen levels, and how diet and lifestyle factors affect estrogen exposure over a lifetime, may help women make more informed decisions about their bodies and their environment.

What is estrogen?
The hormone estrogen works as a chemical messenger in the body. It is essential for normal sexual development and functioning of female organs important for childbearing like the ovaries and uterus. Estrogen also helps regulate a woman’s menstrual cycles. It is necessary for the normal development of the breast. It also helps maintain the heart and healthy bones.

Is estrogen exposure related to a woman’s risk for breast cancer?
Estrogen may be implicated in breast cancer risk because of: 1) its role in stimulating breast cell division; 2) its work during the critical periods of breast growth and development; 3) its effect on other hormones that stimulate breast cell division, and 4) its support of the growth of estrogen-responsive tumors. The BCERF Fact Sheet #09, Estrogen and Breast Cancer Risk: What is the Relationship?, explores how estrogen works and how it might affect the development of breast cancer in greater detail.

Because women with a high lifetime exposure to estrogen may be at higher risk for breast cancer, it is important to understand how lifestyle and environmental factors may affect the levels of estrogen in her body.

“Most observational studies on the use of estrogen-only hormone replacement suggest an increased risk of breast cancer, whereas some show risk neutrality, and a few agree with the reduced risk reported by the WHI,” they wrote.

Causes of breast cancer - the estrogen controversy
No one knows what causes breast cancer, and no one can clearly say why we are seeing an increase in breast cancer cases. More women develop breast cancer than men — about 100 cases in females for every one in a man. Women’s bodies make more estrogen than men’s. Therefore, the conventional wisdom has been that estrogen causes breast cancer.

Some would label this guilt by association; many direct links are missing. One of the biggest missing links is that women’s estrogen levels actually fall as they age, decreasing dramatically after menopause, but the incidence of breast cancer increases with age. The risk ratio that we all hear about - that one in eight women get breast cancer - is for women over 90 years of age. The rate for women in their 50’s is more like one in 50.

So obviously there is much more than estrogen going on in the development of breast cancer, and it is being over-simplistic to think of estrogen as a bad poison when it comes to breast health. Estrogen is a very beneficial hormone in general - it stimulates tissues to grow when we need it to, and it is also a helpful player in response to stress. Let’s explore what we know about the causes of breast cancer, what we don’t know, and what this may mean for you.

While randomized, controlled trials are typically given precedence, “the overall weight of evidence in terms of number of independent studies is also important, and the WHI trial is the only randomized, controlled trial examining estrogen therapy that supports this view,” they added.

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