Individualized ERT Is Urged for Breast Cancer Survivors

ORLANDO—Large numbers of younger breast cancer survivors living with chemotherapy-induced menopause are at increasingly high risk for osteo-porosis and heart disease.

For some of these women, the risk of dying from these estrogen-deficiency diseases, especially heart disease, exceeds the risk of dying from recurrent cancer, so the virtual ban on estrogen-replacement therapy (ERT) for women who have had breast cancer is being reconsidered.

Estrogen’s dual identity was fully on display in a symposium on estrogens and antiestrogens in breast cancer held at the Society of Surgical Oncology’s 52^nd Annual Cancer Symposium.

William C. Wood, MD, Whitehead Professor of Surgery, Emory University School of Medicine, put the discussion into context by reminding the audience that each year 233,000 women die of cardiovascular disease, 65,000 die from complications of hip fractures, and 43,000 die of breast cancer.

“Deaths from cardiovascular disease overwhelm the number of deaths from breast cancer,” he said. The well-known benefits of ERT for postmenopausal women include a 40% reduction in coronary heart disease, a greater than 50% reduction in shoulder and hip fractures, and an “extremely dramatic reduction in mortality from these causes,” he said.

Among women with early node-negative breast cancers smaller than 1 mm, 99% remain free of disease at 10 years. Many of these are younger women, and these relatively young breast cancer survivors may find themselves in an early menopause as a result of chemotherapy.

“Adjuvant therapy with cyclophosphamide/methotrexate/fluorouracil (CMF) induces amenorrhea in 53% of premenopausal women, and this becomes permanent menopause in 86% of women under age 40, and in 96% of women over age 40,” Dr. Wood said.

These women then acquire the increased risk of death from heart disease or hip fracture characteristic of the postmenopausal state. Cardiovascular disease and hip fracture secondary to osteopor-osis are the most serious problems associated with decreased estrogen levels.

ERT has been avoided in these women because of concern that adding estrogen after cancer treatment would increase the risk of cancer recurrence or of new cancers developing. Dr. Wood said that this concern was based largely on data from the Nurses’ Health Study, a study of more than 120,000 nurses, which found a breast cancer relative risk of 1.3 to 1.5 associated with ERT. The absolute risk of breast cancer increased 10% in women not on ERT to 13% to 15% in women who had taken estrogen.

He noted, however, that these data must be interpreted cautiously, since they derive from population data, not from prospective, randomized, controlled clinical trials, and since this was not a dose-adjusted calculation.

Dr. Wood said that two cohort studies of low-dose ERT in women with breast cancer did not find any increased risk associated with low-dose estrogen use. A metaanalysis found some increased risk of breast cancer with ERT doses of 1.25 mg/day of conjugated estrogens, but no increased risk when doses were limited to 0.625 mg/day.

He emphasized that these safety data are “anecdotal and too small” to support broad changes in the current cautious approach to ERT in breast cancer survivors, but he thinks they are strong enough to support a re-evaluation of therapeutic approaches on a case-by-case basis.

“Don’t prescribe ERT for the population of women who have had breast cancer, but do prescribe it for some individual women,” he advised. “Tailor the therapy as specifically as possible to the symptoms and to the risk.” This should include consideration of family history as well as individual symptoms and risk for osteoporosis and heart disease. He also recommended the use of “clearly stated informed consent statements” detailing the discussion of risks and benefits of ERT for breast cancer survivors.