News News
Markers Not Enough "If we had really good therapies, then the markers would be extremely important," said William L. McGuire, M.D., chief of medical oncology at the University of Texas Health Science Center, San Antonio. "We just don't have the drugs to cure breast cancer." A similar situation exists for lung cancer. "Markers by themselves don't do anything," said Bamett Kramer, M.D., associate director of NCI's Early Detection and Community Oncology Programs. "They only can help if they're combined with effective therapy, and the effective therapy part of the equation is what is lacking in relapsed lung cancer." Taube essentially agrees with these assessments but also looks to the future. "Monitoring has the potential for being very important," she said. "You can't wait until you have better treatments to do the research to find the better marker." —By Hugh Mclntosh
Vol. 84, No. 6, March 18, 1992
Hormone Replacement Therapy: Some Answers... More Questions Prolonged estrogen replacement therapy creates worrisome cancer risks, scientists at a recent conference agreed. But accumulating data indicate that longterm ERT also confers major health benefits on postmenopausal women. Several researchers at the Washington, D.C., conference on aging and quality of life addressed the dilemmas faced by physicians and their patients contemplating hormone replacement therapy. For many years, ERT was given to menopausal women only for relatively short periods of time, in order to treat specific symptoms, such as hot flashes. But recent studies showing that women who begin ERT around the time of menopause have a decreased incidence of osteoporosis and heart disease are changing the way in which the hormone is being prescribed.
Downloaded from http://jnci.oxfordjournals.org/ at National University of Singapore on June 27, 2015
A search is under way for better tumor markers to use in screens. Better markers also are needed for monitoring, Taube said, especially in breast cancer. The problem is that most available markers are detectable in serum only after tumor volume has reached a certain level; an ideal marker would be clearly detectable at a very early stage. "If you could catch it earlier," Taube said, "maybe your treatment would be more effective." Another view on handling recurrent breast cancer is to use tissue tumor markers at diagnosis to identify patients in which recurrence is likely and then treat them aggressively. (Tissue tumor markers will be covered in a future Journal News article.) A third view is that serum tumor markers for monitoring are not really necessary until more effective treatments become available.
At the meeting, Brian E. Henderson, M.D., director of the USC's Kenneth Norris, Jr., Comprehensive Cancer Center in Los Angeles, reported significantly increased longevity for women who received long-term estrogen therapy after menopause. Much of this increase can be attributed to decreased mortality from heart disease as well as from thrombotic strokes.
Benefit Unclear But this benefit seems to be present only when estrogen is delivered via the oral route, according to Elizabeth BarrettConnor, M.D., of the University of California, San Diego. And, she added, some of the heart disease decrease seen in studies may result from factors other than the hormone. Women who enroll in prevention studies are likely to be more healthconscious and healthier than the general population, Barrett-Connor noted. In addition, study participants are seen frequently by a physician, and this may further contribute to their superior cardiovascular health. Estrogen's role in maintaining bone density is more clearly established. When started at or soon after menopause, ERT markedly decreases bone loss and consequent osteoporosis.
Adverse Effects
Dr. Elizabeth Barrett-Connor
But estrogen replacement therapy has its down side as well. "I don't think there's any question but that postmenopausal estrogen increases the risk of breast cancer," Barrett-Connor asserted, citing data from several large studies. She added, however, that there is
NEWS
389
News News
Combined Therapy Since studies of hormone replacement therapy have involved estrogen alone, little is known about the effects of progestin taken along with estrogen. However, laboratory evidence suggests that progestins may counteract the increased risk of endometrial cancer. But studies from Europe (where different forms and doses of the hormones are used) suggest that HRT with progestin and estrogen may increase breast cancer risk more than estrogen taken alone. Addition of progestin may also change the benefit side of the risk-benefit ratio. The limited data available suggest that regimens including progestin are likely to produce much less cardiovascular benefit than those that consist only of estrogen. "At this point, I would find it difficult to proceed with a regimen that has not been compared with estrogen replacement therapy alone," Henderson said in an interview. Because heart disease and breast cancer are both much more common and more lethal than endometrial cancer, he noted, adding progestin to an HRT regimen is quite likely to do more overall harm than good.
390
Henderson believes estrogen replacement therapy warrants consideration by all menopausal women without a personal history of breast cancer. But he stops short of recommending that all these women and their physicians decide in favor of the treatment.
Data Needed "If it were administered universally to postmenopausal women, estrogen would be the first prescription drug given as a public health measure rather than for therapy," Henderson said. "We just don't have the clinical trial data to support such use. But we ought to get it." As evidence of the benefits of estrogen replacement therapy mounts, postmenopausal women who have been treated for breast cancer are unhappy about being left out in the cold. Henderson believes that these women might profit from taking tamoxifen, which
Dr. Brian E. Henderson
early data suggest is likely to provide many of the cardiovascular, bone, and other benefits of estrogen, without increasing the risk of breast cancer. "Trials using tamoxifen for this purpose should definitely be performed," Henderson said. At present, though, there is no simple answer for any woman considering hormone replacement therapy, or for her physician advisors. "Each case must be decided on an individual basis," Barrett-Connor said. "It depends on the woman and on her medical history and risk factors."
Clinical Trials These decisions may be somewhat simpler in the future. More than 800 women have been enrolled in a 3-year National Institutes of Health-sponsored trial of hormone replacement therapy. The principal aim of this trial, known as PEPI (Postmenopausal Estrogen/Progestin Interventions), is to compare effects of various HRT regimens on markers related to heart disease, but cancer incidence will be observed as well. NIH also plans to study HRT as part of a major prospective randomized study, known as the Women's Health Initiative, that will follow approximately 70,000 women for 10 years. "We badly need a trial that addresses all the major endpoints, including heart disease, osteoporosis, and cancer," Henderson observed. "I think the issue of hormone replacement therapy is extremely important in terms of its potential impact on quality and quantity of life. The implications are extraordinary." —fly Elaine Blwne
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at National University of Singapore on June 27, 2015
no evidence to date that the increased breast cancer incidence is accompanied by increased mortality from the disease. Most studies show little or no increase in breast cancer incidence for women who take replacement estrogen for just a few years. It is only after 10 to 15 years of use that a modest but fairly consistent increase appears. Estrogen's impact on endometrial cancer risk is greater and more immediate. "Postmenopausal estrogen increases the risk of endometrial cancer," BarrettConnor said. "If you take estrogen for 8 years, you increase your risk about eightfold, if you take it for 10 years, about tenfold, and so forth."
Markers Not Enough "If we had really good therapies, then the markers would be extremely important," said William L. McGuire, M.D., chief of medical oncology at the University of Texas Health Science Center, San Antonio. "We just don't have the drugs to cure breast cancer." A similar situation exists for lung cancer. "Markers by themselves don't do anything," said Bamett Kramer, M.D., associate director of NCI's Early Detection and Community Oncology Programs. "They only can help if they're combined with effective therapy, and the effective therapy part of the equation is what is lacking in relapsed lung cancer." Taube essentially agrees with these assessments but also looks to the future. "Monitoring has the potential for being very important," she said. "You can't wait until you have better treatments to do the research to find the better marker." —By Hugh Mclntosh
Vol. 84, No. 6, March 18, 1992
Hormone Replacement Therapy: Some Answers... More Questions Prolonged estrogen replacement therapy creates worrisome cancer risks, scientists at a recent conference agreed. But accumulating data indicate that longterm ERT also confers major health benefits on postmenopausal women. Several researchers at the Washington, D.C., conference on aging and quality of life addressed the dilemmas faced by physicians and their patients contemplating hormone replacement therapy. For many years, ERT was given to menopausal women only for relatively short periods of time, in order to treat specific symptoms, such as hot flashes. But recent studies showing that women who begin ERT around the time of menopause have a decreased incidence of osteoporosis and heart disease are changing the way in which the hormone is being prescribed.
Downloaded from http://jnci.oxfordjournals.org/ at National University of Singapore on June 27, 2015
A search is under way for better tumor markers to use in screens. Better markers also are needed for monitoring, Taube said, especially in breast cancer. The problem is that most available markers are detectable in serum only after tumor volume has reached a certain level; an ideal marker would be clearly detectable at a very early stage. "If you could catch it earlier," Taube said, "maybe your treatment would be more effective." Another view on handling recurrent breast cancer is to use tissue tumor markers at diagnosis to identify patients in which recurrence is likely and then treat them aggressively. (Tissue tumor markers will be covered in a future Journal News article.) A third view is that serum tumor markers for monitoring are not really necessary until more effective treatments become available.
At the meeting, Brian E. Henderson, M.D., director of the USC's Kenneth Norris, Jr., Comprehensive Cancer Center in Los Angeles, reported significantly increased longevity for women who received long-term estrogen therapy after menopause. Much of this increase can be attributed to decreased mortality from heart disease as well as from thrombotic strokes.
Benefit Unclear But this benefit seems to be present only when estrogen is delivered via the oral route, according to Elizabeth BarrettConnor, M.D., of the University of California, San Diego. And, she added, some of the heart disease decrease seen in studies may result from factors other than the hormone. Women who enroll in prevention studies are likely to be more healthconscious and healthier than the general population, Barrett-Connor noted. In addition, study participants are seen frequently by a physician, and this may further contribute to their superior cardiovascular health. Estrogen's role in maintaining bone density is more clearly established. When started at or soon after menopause, ERT markedly decreases bone loss and consequent osteoporosis.
Adverse Effects
Dr. Elizabeth Barrett-Connor
But estrogen replacement therapy has its down side as well. "I don't think there's any question but that postmenopausal estrogen increases the risk of breast cancer," Barrett-Connor asserted, citing data from several large studies. She added, however, that there is
NEWS
389
News News
Combined Therapy Since studies of hormone replacement therapy have involved estrogen alone, little is known about the effects of progestin taken along with estrogen. However, laboratory evidence suggests that progestins may counteract the increased risk of endometrial cancer. But studies from Europe (where different forms and doses of the hormones are used) suggest that HRT with progestin and estrogen may increase breast cancer risk more than estrogen taken alone. Addition of progestin may also change the benefit side of the risk-benefit ratio. The limited data available suggest that regimens including progestin are likely to produce much less cardiovascular benefit than those that consist only of estrogen. "At this point, I would find it difficult to proceed with a regimen that has not been compared with estrogen replacement therapy alone," Henderson said in an interview. Because heart disease and breast cancer are both much more common and more lethal than endometrial cancer, he noted, adding progestin to an HRT regimen is quite likely to do more overall harm than good.
390
Henderson believes estrogen replacement therapy warrants consideration by all menopausal women without a personal history of breast cancer. But he stops short of recommending that all these women and their physicians decide in favor of the treatment.
Data Needed "If it were administered universally to postmenopausal women, estrogen would be the first prescription drug given as a public health measure rather than for therapy," Henderson said. "We just don't have the clinical trial data to support such use. But we ought to get it." As evidence of the benefits of estrogen replacement therapy mounts, postmenopausal women who have been treated for breast cancer are unhappy about being left out in the cold. Henderson believes that these women might profit from taking tamoxifen, which
Dr. Brian E. Henderson
early data suggest is likely to provide many of the cardiovascular, bone, and other benefits of estrogen, without increasing the risk of breast cancer. "Trials using tamoxifen for this purpose should definitely be performed," Henderson said. At present, though, there is no simple answer for any woman considering hormone replacement therapy, or for her physician advisors. "Each case must be decided on an individual basis," Barrett-Connor said. "It depends on the woman and on her medical history and risk factors."
Clinical Trials These decisions may be somewhat simpler in the future. More than 800 women have been enrolled in a 3-year National Institutes of Health-sponsored trial of hormone replacement therapy. The principal aim of this trial, known as PEPI (Postmenopausal Estrogen/Progestin Interventions), is to compare effects of various HRT regimens on markers related to heart disease, but cancer incidence will be observed as well. NIH also plans to study HRT as part of a major prospective randomized study, known as the Women's Health Initiative, that will follow approximately 70,000 women for 10 years. "We badly need a trial that addresses all the major endpoints, including heart disease, osteoporosis, and cancer," Henderson observed. "I think the issue of hormone replacement therapy is extremely important in terms of its potential impact on quality and quantity of life. The implications are extraordinary." —fly Elaine Blwne
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at National University of Singapore on June 27, 2015
no evidence to date that the increased breast cancer incidence is accompanied by increased mortality from the disease. Most studies show little or no increase in breast cancer incidence for women who take replacement estrogen for just a few years. It is only after 10 to 15 years of use that a modest but fairly consistent increase appears. Estrogen's impact on endometrial cancer risk is greater and more immediate. "Postmenopausal estrogen increases the risk of endometrial cancer," BarrettConnor said. "If you take estrogen for 8 years, you increase your risk about eightfold, if you take it for 10 years, about tenfold, and so forth."
