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Key Words

Breast cancer, LHRH agonists, ovary suppression. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

In premenopausal women with hormone-sensitive breast cancer, drugs that stop the ovaries from functioning - thus shutting off the body’s main source of the hormone estrogen - reduced the rates of relapse and of death following relapse when given in addition to tamoxifen, chemotherapy, or both.

Source

The Lancet, May 19, 2007 (see the journal abstract ⁴).

Background

Women with breast cancer commonly receive additional, or adjuvant, treatment after surgery to reduce the risk of a relapse. One option for younger women whose tumors grow in response to one or both of the hormones estrogen and progesterone (hormone-sensitive tumors) is drug treatment to stop the ovaries from functioning (ovarian suppression). In women who have not yet reached menopause, the ovaries produce most of the body’s estrogen.

Drugs called LHRH agonists can be used to induce ovarian suppression. (LHRH stands for luteinizing-hormone-releasing hormone, which is a kind of hormone that controls sex hormones in men and women.) LHRH agonists work differently than the anti-estrogen drug tamoxifen, which many breast cancer patients now take because of evidence showing that it reduces the risk of a recurrence.

Although researchers have conducted numerous studies to assess the effects of LHRH agonists in premenopausal women with breast cancer, none of these studies have proven that the drugs delayed or prevented relapse or extended patients’ lives.

The study described here is a meta-analysis, in which researchers combine data from numerous other studies and summarize the combined results. This technique may be used to try to answer a research question when multiple studies have reached differing conclusions. In the current study, an international group of researchers conducted a meta-analysis of studies of LHRH agonists to try to conclusively determine whether premenopausal women with breast cancer benefited from treatment with these drugs.

The Study

The researchers combined data for nearly 12,000 premenopausal women who had been enrolled in 16 clinical trials of LHRH agonists. The trials took place between 1987 and 2001 in the United States, Japan, and six European countries.

The median patient age was about 43. Most had early-stage breast cancer. A small number of women received LHRH agonists as their only additional treatment after surgery. Most women received LHRH agonists in addition to either tamoxifen or chemotherapy or both. The duration of treatment with LHRH agonists varied from 18 months to five years. The median length of follow-up across all of the trials was about seven years.

A total of 9,022 women (75.8 percent) had hormone-sensitive tumors. Within this group, more than 90 percent had tumors fueled by estrogen; the remainder, by progesterone.

The principal investigator for the meta-analysis was epidemiologist Jack Cuzick, Ph. D., of the University of London in the United Kingdom.

Results

Overall, adding LHRH agonists to tamoxifen, chemotherapy, or both reduced the rate of relapse by 12.7 percent and the rate of death after relapse by 15.1 percent.

Limitations

Although today tamoxifen is considered a standard additional therapy for women with hormone-sensitive tumors, it was not given as standard treatment in any of the trials included in this meta-analysis, noted Nancy E. Davidson, M.D., professor of oncology at Johns Hopkins University in Baltimore, Md., a co-author of the meta-analysis who discussed the findings at the 2007 American Society of Clinical Oncology annual meeting in Chicago.

Also, she noted that many of the women in the meta-analysis who received chemotherapy were treated with the drugs cyclophosphamide, methotrexate, and fluorouracil (CMF), a regimen that is rarely used anymore. Most breast cancer patients who receive chemotherapy are now treated with drugs such as doxorubicin (Adriamycin®), epirubicin (Ellence®), paclitaxel (Taxol®), and docetaxel (Taxotere®), which have been shown in clinical trials to be more effective than CMF.

A further limitation, Davidson observed, is that LHRH agonists were used for as short a time as 18 months in some trials and as long as five years in others. “The optimal duration of LHRH therapy is unknown,” she said.

Comments

Despite these caveats, “LHRH agonists are very clearly effective when used” in patients with hormone-sensitive tumors, Davidson concluded.

U.S. oncologists do not routinely use LHRH agonists in the treatment of premenopausal breast cancer, said Jennifer Eng-Wong, M.D., a medical oncologist with the National Cancer Institute’s Center for Cancer Research. Premenopausal patients with hormone-sensitive breast cancer would, however, be treated with tamoxifen with or without chemotherapy.

Surgery and radiation may also be used to block ovarian function in premenopausal women with breast cancer, noted Eng-Wong. A possible advantage of using an LHRH agonist to induce ovarian suppression is that the effect may be reversible when the patient stops taking the drug, she added, which may allow the woman to become pregnant. By contrast, using surgery or radiation to suppress ovarian function is irreversible and induces early menopause.

Glossary Terms

A drug that triggers an action from a cell or another drug.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

Luteinizing hormone-releasing hormone. A hormone that stimulates the production of sex hormones in men and women. Also called luteinizing hormone-releasing hormone.

A statistics term. The middle value in a set of measurements.

The time of life when a woman's menstrual periods stop. A woman is in menopause when she hasn't had a period for 12 months in a row. Also called change of life.

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

Having to do with the time before menopause. Menopause ("change of life") is the time of life when a woman's menstrual periods stop permanently.

A type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone can also be made in the laboratory. It may be used as a type of birth control and to treat menstrual disorders, infertility, symptoms of menopause, and other conditions.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called standard of care or best practice.