ORLANDOLarge 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.
Estrogens dual identity was fully on display in a symposium on
estrogens and antiestrogens in breast cancer held at the Society of
Surgical Oncologys 52nd 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
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
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
Dont 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