Use of Hormone Replacement Therapy Should be Considered When Evaluating Breast Cancer Severity and Determining Treatment
An important indicator of a more aggressive form of breast cancer appears to be present in less aggressive breast cancers in many women who have used hormone replacement therapy (HRT), according to researchers at Rush-Presbyterian-St. Luke's Medical Center.
As a result, some women may receive chemotherapy treatment when an approach with fewer side effects might be equally effective and less traumatic, according to Dr. Melody Cobleigh, director of the Comprehensive Breast Center at Rush.
This was one of the interesting findings from a study that compared the prognostic characteristics of breast cancers in women who have used HRT and those who have never used HRT. The study by Cobleigh and her colleagues involved 331 post-menopausal women. The results of her study are reported in the April 28 issue of the Journal of the American Medical Association.
S-phase (the percent of cells that are synthesizing DNA) is one of six prognostic characteristics commonly measured in breast cancers at the time of diagnosis. A high S-phase has generally been considered a marker or indicator of an aggressive breast cancer and a poor prognosis. The new research shows a correlation between HRT use and S-phase.
"The association has not been made before, and a high S-phase for patients using HRT may not mean the same thing as a high S-phase in women who are not using HRT," said Cobleigh. "A high S-phase in women who have not taken HRT may be of greater concern as a prognostic factor for breast cancer outcome."
Most physicians believe that the benefits of hormone replacement therapy for post-menopausal women outweigh the slight increase in the risk for breast cancer that is associated with long term use of the hormones. And according to most studies, women who do develop breast cancer while taking HRT have a better survival rate than women who have breast cancer and have never taken HRT.
Cobleigh and her Rush colleagues undertook the study in an attempt to understand this paradox. To study the characteristics of breast cancers that developed in these women and to compare them to those who never used HRT, she evaluated six different prognostic factors and found that women who developed breast cancer at the time they were taking HRT had a high S-phase.
To further evaluate the finding, she divided the study subjects according to whether their cancers contained the estrogen receptor, a protein on the surface of some breast cancer cells that binds to estrogen.
Cobleigh found that S-phase was affected by HRT only in women whose cancers contained the estrogen receptor. This finding follows earlier animal laboratory work, which showed that estrogen affects the ability of breast cancer cells to divide and multiply only if they contain the estrogen receptor.
But in 8 of 9 earlier studies, women diagnosed with breast cancer while taking HRT had a better survival rate than those who did not take HRT.
How can the worse outlook of high S-phase cancers in general be reconciled with the better outlook of breast cancers that develop in women who use HRT?
"Hormone replacement therapy may not cause breast cancer, but for women who do develop breast cancer that is estrogen receptor positive, it may bring their tumor to light sooner than it would otherwise become evident because they are taking a medication that makes their tumor grow faster," said Cobleigh.
This may explain why some women who have had HRT and get breast cancer live longer following therapy. It may also explain, in part, why women who take HRT have a slightly increased risk of breast cancer.
"These finding are important for physicians because they demonstrate another level of complexity in understanding prognostic factors in breast cancer. The woman who is using HRT and has a high S-phase, estrogen receptor-positive cancer may have a very different prognosis than a woman with similar tumor characteristics who has not used HRT," explained Cobleigh. "This is a hypothesis, however, that needs to be tested in a cooperative group study."
Physicians frequently recommend chemotherapy for such patients even when their tumors are very small and lymph nodes are not involved. This research suggests that women who are diagnosed with estrogen receptor-positive breast cancers while taking HRT may have an artificial increase in S-phase.
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