Estrogen Alternatives in Breast Cancer Patients

WASHINGTON—A consensus conference convened to assess the treatment of estrogen deficiency symptoms in breast cancer survivors has recommended that physicians treat these women with “tailored treatment strategies” that avoid the use of estrogen but provide its short-term and long-term benefits.

“New approaches have been developed recently that allow the use of surrogates for estrogen to gain the benefits of estrogen without using estrogen itself,” said Richard J. Santen, MD, professor of medicine at the University of Virginia (UVA).

The three-day conference was sponsored by the UVA Health Sciences Center in Charlottesville, the Susan G. Komen Breast Cancer Foundation, the Hormone Foundation, the Endocrine Society, and the Canadian Breast Cancer Research Initiative. Its recommendations were released at a press conference, and a full report will be published in a forthcoming issue of the journal ONCOLOGY.

Dr. Santen said that the conference grew out of the recognition that “practicing oncologists were basically telling their breast cancer patients with menopausal symptoms: ‘The only thing available is estrogen, and you cannot take estrogen; therefore, put up with your symptoms.’ Yet a group of us knew that there were a number of new medications becoming available and new ways to treat patients independently of estrogen.”

He cited five medical problems related to menopause that physicians commonly treat with estrogen replacement therapy: (1) vasomotor symptoms such as hot flashes, sweats, and frequent awakening from sleep; (2) urogenital symptoms that include dry vagina, pain on intercourse, frequent urinary tract infections, and involuntary loss of urine or incontinence; (3) osteoporosis; (4) a markedly increased risk of heart disease; and (5) a disruption in the feeling of well-being that includes problems with memory, depression, and sleep.

The key to tailored treatment strategies, he said, is to determine exactly what problems a women is experiencing and to find an effective way to deal with them that does not require systemic estrogen.

For example, potent drugs are available to lower cholesterol levels and reduce a woman’s risk of a heart attack. With respect to osteoporosis, a consensus developed that the bisphosphonates are similar in efficacy to estrogen in increasing bone and preventing fractures.

Other approaches include the use of a vaginal estrogen ring, introduced in the United States and Canada this year, to treat urogenital problems locally, and the drugs clonidine and megestrol acetate (Megace) to cool hot flashes.

Researchers are working to find drugs that provide the positive benefits of estrogen replacement therapy without the negative effects on breast tissue, noted Henry Burger, MD, director of Prince Henry’s Institute of Medical Research, Melbourne, Australia.

“The exciting new development has been a class of compounds with target-site-specific actions, known as selective estrogen receptor modulators,” he said.

The best known of these experimental new drugs is raloxifene, Dr. Burger said. Data from 2 years of phase II raloxifene trials indicate that “it has good effects as an antiestrogen in patients with advanced estrogen-sensitive breast cancer, and shows promise of being suitable for osteoporosis prevention and treatment, with beneficial effects on heart disease risk and on breast and uterine cancer risks.”

Dr. Burger said that studies using raloxifene to prevent osteoporosis are underway in about 7,000 women, and the preliminary bone data are favorable—showing effects similar to, but somewhat smaller than, those of estrogen.

He added that some plants, notably soybeans, contain substances called phytoestrogens that are similar to raloxifene, and that some women take phytoestrogen preparations sold in health food stores.

The consensus conference expressed concern about this and other herbal medicines, stating: “We lack information about effectiveness, safety, and toxicity. . . . Some herbs are not helpful and may, in fact, be dangerous. Clearly, clinical trials are needed and wanted by women.”

Other Recommendations

The conference also recommended the following:

• Starting research trials to evaluate use of estrogens or estrogen alternatives in selected groups of women in whom they are likely to be beneficial and safe.

“Carefully designed trials to explore the effectiveness and the safety of estrogens and/or progesterone in women with a previous diagnosis of breast cancer who are also receiving tamoxifen [Nolvadex] should be undertaken,” said Kathleen Pritchard, MD, professor of medicine at the University of Toronto.

She said that the underlying biology of this situation suggests that the combination of tamoxifen with estrogen or progesterone could potentially relieve symptoms without increasing the risk of breast cancer recurrence.

• Planning studies to exploit the highly favorable properties of selective estrogens.
• Forging an immediate “Partnership for Progress” between patient advocate groups and health professionals to facilitate research and education about treatment options.
• Exploring the establishment of a patient registry to determine what patients are currently doing and thinking about the problem.