Medical Oncologist's Response to Luteinizing Hormone-Releasing Hormone (LH-RH) Agonist Study

  • Breast Cancer News Editor's Note: Science and health news outlet EurekAlert! published yesterday an interesting summary of a Lancet study on luteinizing hormone-releasing hormone (LH-RH) agonists, drugs that decrease the level of estrogen and other sex hormones in women.  LH-RH agonists for breast cancer treatment are used in Europe and Australia but rarely in the United States, which may explain why the study, published in a leading British medical journal got so little press in the States. Nevertheless, the findings are notable and worth reviewing. Read on for a summary of the news release and Dr. Alvaro Pereira-Rico's analysis of the breast cancer news. Also read HealthDay's news coverage in the article: New Hormone Treatment Fights Certain Breast Cancers
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    Background on LH-RH Agonists:

    A luteinizing hormone-releasing hormone, or LH-RH, is a hormone that stimulates the production of sex hormones (e.g. estrogen, testosterone) in men and women.

    LH-RH agonist is a drug that prevents the secretion of sex hormones. In women, LH-RH agonists cause the level of estrogen and other sex hormones to fall.

    Here's a summary of the EurekAlert report:

    Alternative Hormone Treatment Could Help Fight Against Breast Cancer

    Luteinizing-hormone-releasing hormone (LHRH) agonists, drugs that decrease estrogen and other sex hormone levels in women, have proven effective when used alone or combined with existing treatments used in the fight against hormone receptor positive breast cancer. The authors's conclusions were published in this week's edition of The Lancet, a leading British medical journal.

    Luteinizing hormone is produced in the pituitary gland and stimulates ovulation and the production of estrogen. LH-RH agonists are molecules which mimic the action of luteinizing hormone by binding to the same receptors within the pituitary gland. This substitutive binding blocks the signal for the ovary to produce estrogen, a sex hormone known to stimulate the growth of breast cancer.

    Professor Jack Cuzick, Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary's School of Medicine and Dentistry, University of London, UK and colleagues found that for hormone receptor-positive patients, LH-RH agonists were as effective as chemotherapy treatment used in these trials.

    Treatment with LH-RH agonists combined with chemotherapy or tamoxifen gave an additional benefit, reducing recurrence of breast cancer by nearly 13% and death after recurrence by 15%. Howeve,r the combined treatments only showed the additional benefit in women under 40. LH-RH agonists were ineffective for hormone receptor-negative tumors.

    The researchers did a meta-analysis (a study which combines results from previous trials) of 16 trials and obtained data for 11,906 pre-menopausal women with early breast cancer. The authors conclude: "The results of our analysis show that LH-RH agonists provide an effective additional class of agents for the treatment of premenopausal women with hormone-sensitive breast cancer."

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    In an accompanying Comment, Drs Nicholas Wilcken and Martin Stockler, Department of Medical Oncology, Westmead and Napean Hosptials andUniversity of Sydney, NSW, Australia and NHMRC Clinical Trials Centre, University of Sydney and Sydney Cancer Centre, Royal Prince Alfred and Concord Hospitals, NSW, Australia, say: "In women with higher-risk disease, chemotherapy followed by tamoxifen should still be the standard approach, with the addition of an LH-RH analogue a reasonable consideration for those who remain premenopausal.

    "A century of research has taught us much about endocrine therapy for breast cancer, but the most important lessons about adjuvant ovarian suppression will be learnt over the next decade."

    Read Dr. Alvaro Pereira-Rico's Response:

    First, let me make a point regarding the title of this news story. The word alternative might imply for some patients a non-standard, “integrative medicine approach”.


    This article refers to a well-known but not precisely defined approach (as with phase III randomized clinical trials) for pre-menopausal hormone receptor positive breast cancer. LH-RH for breast cancer is used mostly in Europe and Australia, but rarely in the USA. The rationale for its use is very clear: inhibit the hormones (in the brain) that stimulate the production of estrogen, and the main driving force of breast cancer growth will be severely diminished.


    As with all the hormonal agents in breast cancer, it only works in tumors that have hormone receptors. And it is not surprising that it works best in pre-menopausal women, who have higher estrogen levels than post-menopausal women. And since breast cancer is more aggressive in younger women, it makes sense that adding a different line of therapy to the standard of care benefits this group of patients. Although I have not read the original paper it seems to me that using LH-RH agonists in addition to chemotherapy and tamoxifen (“peripheric” antiestrogen) MIGHT give a pre-meopausal woman with hormone receptor positive breast cancer the best chance for permanent cure. But as stated in the last paragraph, this approach is not yet a standard of care. There are a large number of on-going adjuvant trials using hormonal agents, which for sure will change how we use LH-RH agonists in breast cancer.


    I hope you find this informative and implore you to speak with your physician about your specific situation.

Published On: May 18, 2007