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In December 2006, attendees of the 29th Annual San Antonio Breast Cancer Symposium received a report that the incidence of breast cancer in the United States dropped 7 percent in 2003. While the impact of this finding is profound, since the data were reported researchers have been trying to explain the reasons behind the decline.
The decline in breast cancer and the decline in hormone use could be directly correlated.
The decline in breast cancer and the decline in hormone use could be directly correlated.
Many experts suggest the decline may be related to a decrease in hormone replacement therapy (HRT), which started in mid-2002. The dramatic decrease in HRT followed the release of a Women’s Health Initiative (WHI) report in June 2002. The initiative found that postmenopausal women who took hormone therapy had an increased risk of breast cancer. At that time, nearly half of all women on hormone therapy stopped taking it. Researchers think the decline in breast cancer and the decline in hormone use could be directly correlated.
In an effort to address the most common causes of death, disability and weakened quality of life in postmenopausal women, the National Institutes of Health established the WHI in 1991. The WHI is a collection of studies and clinical trials lasting 15 years. This multi-million dollar endeavor is one of the largest U.S. prevention studies of its kind.
The WHI was made up of two separate studies:
In both studies, women were randomly assigned to receive either hormone therapy or a placebo. The studies have concluded, but the women in the studies will participate in a follow-up phase until 2010.
Results were published from the E-alone trial in JAMA, the Journal of the American Medical Association, on April 12, 2006. Those results were compared to the results of the E+P trial for a more comprehensive picture.
The combined findings of these trials show that women with prior hysterectomy do not have an increased risk of breast cancer for at least seven years after starting estrogen-alone therapy. However, women with a uterus who use combined estrogen and progestin had an increased risk of breast cancer after five years of therapy.
Breast cancer occurs when a cell of breast origin begins to divide and grow at an abnormal rate. The cells invade tissues in the breast and may spread to the lymph nodes or to other parts of the body (metastasis).
Breast cancer can be detected via physical exam and mammogram. In most cases, doctors are unsure what triggers abnormal cell growth in breast tissue; however, it is known that more than two-thirds of breast cancer is driven by estrogen, which may be related to the development and progression of breast cancer.
In 5-10 percent of patients, breast cancer is related to genetic or inherited factors. Other risk factors include aging, diet, being overweight, and the use of hormone therapy containing estrogen for four or more years. However, most women who get breast cancer do not have clearly identified risk factors, and many women who have known risk factors never get breast cancer.
The two main types of hormone replacement therapy are estrogen alone (also called ERT or estrogen replacement therapy) and estrogen plus progestin (or combined therapy). Estrogen and progesterone are both hormones that are produced by a woman’s ovaries. During menopause, the ovaries no longer produce adequate amounts of hormones and many women choose to take hormone therapy to replace the lost hormones, thus relieving some of the symptoms of menopause.
There is still much debate among specialists on the risks and benefits of hormone therapy. For women who experience moderate to severe hot flashes or other menopausal symptoms, the benefits of short-term therapy typically outweigh the potential risks. More follow-up is needed, but short-term, low-dose therapy may offer a balance between benefits and risks.
Each woman is different and it is important to talk with your doctor about your individual risks. If you decide to take hormone therapy, continue to review the risks and benefits with your doctor one to two times a year. Depending on your age, regimen and symptoms, your doctor may modify your dosage.
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Until the year 2003, breast cancer incidence had been steady. In 2003, there was a sharp 7 percent drop in the incidence of breast cancer, which translates to around 14,000 fewer cases in 2003.
When researchers looked at the different patient subgroups, it was evident that the group which accounted for most of the drop was that of women above age 50 with the type of breast cancer that expresses the estrogen receptor.
“We do not have conclusive evidence that discontinuation of HRT is responsible for the drop in breast cancer incidence, but it seems plausible."
Just preceding the start of breast cancer decline was the release of the WHI study in mid-2002. This study reported an increased risk of breast cancer in women taking hormone replacement therapy (HRT), and quickly afterward the number of postmenopausal women (those above age 50) taking HRT dropped from 30 percent to 15 percent. The general view is that this marked drop may have directly contributed to the decreased breast cancer incidence that followed.
We do not have conclusive evidence that discontinuation of HRT is responsible for the drop in breast cancer incidence, but it seems plausible. There are other potential contributing factors including:
These two factors may have contributed some but are unlikely to have resulted in the degree of breast cancer decline.
One important point to make is that the breast cancer decline started almost immediately after the release of the WHI study with a 1 percent decline per month starting July 2002. We know that HRT may stimulate existing breast cancers, and therefore it is possible the early decline in breast cancer incidence may reflect arrested growth tumors or perhaps some tumors are regressing. To isolate these different effects, we need longer follow-up to determine how the incidence trend behaves. Breast cancer may not be going away–it may just take longer to show.We certainly need more data and morefollow-up to tell exactly what is contributing to the decline. Latest U.S. incidence data for the year 2004 were released in April 2007 and published in the New England Journal of Medicine. The data showed a leveling off compared to the 2003 rate with little additional decline.
Estrogen production declines naturally in postmenopausal women because of the physiologic loss of ovarian function. The term hormone “replacement” therapy does not reflect the natural physiology and can therefore be misleading. “Hormone therapy” is a more accurate term. After menopause, body fat tissue will continue to produce a very small amount of estrogen. Low estrogenis part of the healthy, natural state of postmenopause.
Estrogen does play an important role in skin and bone health, so it is important to talk to your doctor about how to maintain bone health after menopause.
If a woman undergoes surgical removal of her ovaries before natural menopause, her estrogen will drop sharply. In these younger women, estrogen “replacement” therapy is recommended to replace the estrogen lost.
The WHI only studied women between the ages of 50-69, so the effect of HRT on premenopausal women is unclear. Estrogen does help protect against bone loss and the benefits may outweigh the risks for younger women who take estrogen therapy, but this area needs further research.
Over the next few years, researchers will continue to examine changes in breast cancer rates to see whether the breast cancer decline will continue. Potential risk factors for breast cancer development will continue to be examined, but the clearest factor appears to be hormone therapy use. The picture should become clearer in the next several years, and we are likely to see a lot more reports on the change in breast cancer epidemiology.
If the trend of breast cancer decline continues and the decrease continues to affect postmenopausal women (those over 50), we may see a decrease in the median age of breast cancer diagnosis. In other words, we may see a relatively younger population of breast cancer. This may occur because of the decreased representation of women over the age of 50 who are at lower risk after discontinuation of HRT.
The decline in breast cancer is great news regardless of the cause. Breast cancer is one of the more treatable cancers, but it does affect more than 200,000 women a year and 40,000 women a year still die from breast cancer. If we have 14,000 fewer women a year who get breast cancer, it is wonderful and very much welcome news.
Dr. Massarweh is a medical oncologist specializing in breast cancer and a member of the UK Markey Cancer Center. He is also an assistant professor of medicine at UK College of Medicine.
Each issue of Advances & Insights summarizes an important piece of medical news, accompanied by commentary from a UK expert.
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