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Million Women Study Finds Increased Breast Cancer Risk Among Women Who Use Hormone Replacement Therapy (HRT) (dateline August 15, 2003)

Results from the Million Women Study, a United Kingdom research project investigating reproductive and lifestyle factors affecting women’s health, has found that women who use or have used hormone replacement therapy (HRT) are more likely to develop breast cancer, compared to women who have never used HRT. This is the largest study to date linking the menopausal treatment to an increased breast cancer risk. Researchers noted that the risk of breast cancer was higher among women who used combined estrogen/progestin forms of HRT, rather than estrogen alone. The results of this study underscore the need for women to talk with their physicians before beginning/continuing an HRT regimen. Women who suffer from hot flashes or other menopausal symptoms may also wish to consider alternative remedies, depending on their personal risk of breast cancer.

Hormone replacement therapy (HRT) is synthetic estrogen and progesterone (called progestin) designed to "replace" a woman's depleting hormone levels as she nears menopause. Decreased levels of estrogen may cause hot flashes, vaginal dryness, sleep disturbances, or other bothersome menopausal symptoms. HRT helps to relieve these and other effects. Past research has shown that HRT may also help prevent osteoporosis, heart disease, short-term memory loss, depression, and other diseases in post-menopausal women. However, recent research has found that HRT may not provide these benefits and may pose other risks, most notably an increased risk of breast cancer.

There are several different regimens of HRT prescribed to women. Most women who have not had their uteruses removed prior to treatment take a combined estrogen/progestin form of HRT because estrogen alone can increase the risk of uterine cancer. Women who have had their uteruses removed do not need to take progestin and typically take estrogen alone.

The Million Women Study is a collaborative effort of the charity Cancer Research UK and the National Health Service Breast Screening Programme (United Kingdom), with additional funding from the UK Medical Research Council. The study is investigating the link between HRT, breast cancer, and other health issues. Researchers are also studying a variety of other health areas, including diet, childbirth, breastfeeding, vitamin and mineral supplement use, oral contraceptive use, and family history of illness.

The results of the Million Women Study were published in the August 9, 2003 issue of The Lancet. Led by Valerie Beral of the Cancer Research UK Epidemiology Unit in Oxford, England and colleagues, the study reviewed medical data from over one million women ages 50 to 64 who enrolled in the study between 1996 and 2001. Approximately 50% of the women were using or had used HRT. The Million Women Study included 9,364 cases of invasive breast cancer and 637 breast cancer deaths over the follow-up periods (2.6 years and 4.1 years respectively).

Results showed that current and recent use of HRT increased the risk of breast cancer. Specifically, women who used combined estrogen/progestin HRT regimens had a substantially higher risk of breast cancer, compared to women who used estrogen alone. The increased risk of breast cancer appeared to decrease after a few years off treatment. Other key findings include the following:

  • Post-menopausal women who used combined estrogen/progestin regimens of HRT were twice as likely to develop breast cancer, compared to women who never used HRT;
  • Women who used estrogen alone were 30% more likely to develop breast cancer and women who used tibolone (a steroid that combines estrogen, progesterone and androgene activity, comparable to standard HRT regimens) were 45% more likely to develop breast cancer, compared to women who never used HRT;
  • Women who current used HRT had a 22% increased risk of death from breast cancer, compared to women who never used HRT (these last results need further confirmation);

Based on these findings, the charity Cancer Research UK estimates that for every 1,000 post-menopausal women who use HRT for 10 years, beginning at age 50, there will be five additional cases of breast cancer among women using estrogen alone and 19 additional cases among women using estrogen/progestin combination regimens. Overall, Cancer Research UK estimates that HRT contributed to an additional 20,000 cases of breast cancer during the past decade, 15,000 of which resulted from combined estrogen/progestin HRT regimens.

With this new information, many medical experts and women are trying to weigh the true benefits and risks of HRT. HRT is undoubtedly the most effective way to treat hot flashes and other bothersome, sometimes debilitating, symptoms of menopause. However, research continues to show a link between HRT and an increased risk of breast cancer. Furthermore, recent research is also questioning the once-accepted benefits of HRT as a protector against heart disease and osteoporosis. For an in-depth examination of accepted facts and debating points on HRT, please click here.

This latest study also highlights the possible danger of combined estrogen/progestin regimens of HRT. While combined regimens are typically recommended for women who still have their uteruses intact, lead researcher Valerie Beral suggests that women discuss regimen options with their physicians. Given the newly discovered risk of combined hormone regimens, the slight increased risk of uterine cancer may be more favorable to some women, versus the more substantial risk of breast cancer, depending on their personal medical histories.

It is important to note, however, that despite these new study results, HRT may still be appropriate for some women. Women who suffer from severe menopausal symptoms and have a low personal risk of breast cancer may wish to consider/continue HRT for a short duration. A thorough discussion of these issues with a physician is recommended for all women considering or currently taking HRT.

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