New Breast Cancer Drugs Offer Alternative to Tamoxifen
By Mark Bloom, HealthDay Reporter
SUNDAY, April 10 (HealthDay News) -- Tamoxifen's long reign as the queen of breast-cancer treatments is being challenged by three heiress presumptives -- drugs known as aromatase inhibitors.
For the past three decades the use of tamoxifen has been one of the few relatively easy decisions for most postmenopausal women after surgery or other treatment for breast cancer. Tamoxifen, an anti-estrogen drug, has helped prevent both recurrence of the original cancer or disease in the other breast, or both, for women whose tumors are estrogen-receptive positive.
The drug blocks estrogen's effects on breast tissue, stopping or preventing the growth of cancer. It is used to treat women with metastatic breast cancer -- disease that has spread -- or to reduce the risk of recurrence after treatment for early stage breast cancer.
The decision to take tamoxifen was usually easy because there was no other treatment. It was tamoxifen or nothing, and for most women nothing was unacceptable. Tamoxifen had a remarkable benefit for five years but then the benefit declined markedly. Ten years of tamoxifen, it was shown, was no better than five years. Nonetheless, tamoxifen was not without drawbacks even during its years of benefit, such as statistically having an extra rate of endometrial cancer in women taking it.
Still, according to Dr. Neil Love of the University of Miami, "You can make a pretty good argument that this little pill has prevented more suffering from cancer than perhaps any other systemic agent in the history of oncologic therapy."
Now with the introduction of aromatase inhibitors, a newer class of anti-estrogens, the picture has changed dramatically, and women and their oncologists have choices. For early treatment after surgery -- known as adjuvant therapy -- tamoxifen is merely one of the choices and not necessarily the leading one.
To be sure, 30 years' experience with tamoxifen are compelling, and many women are sticking with the tried and true. After all, therapy with tamoxifen has reduced new disease in the other breast by 47 percent, for instance. The risk of endometrial cancer in women taking tamoxifen was small but real. There were about half as many extra cases of endometrial cancer as there were cases of cancer prevented in the other breast.
"The rational decision at the moment is to consider tamoxifen still the gold standard," according to Dr. Michael Baum, a British cancer doctor who was a principal investigator on a key study of the aromatase inhibitor known as anastrozole, that was published at the beginning of the year in The Lancet.
Yet, Baum and others believe the study suggests that the torch is passing. This and other studies are accumulating to show that the aromatase inhibitors are safer than tamoxifen and outdo it in prevention of recurrence or disease in the other breast. What's more, one of the aromatase inhibitors, a drug called Femara, or letrozole, has been shown to take over after five years of tamoxifen and keep the benefit going. The other two may do the same.
Some doctors would now start with Arimidex or the others instead of tamoxifen. Others show data suggesting that a prudent approach is to switch to an aromatase inhibitor, perhaps Aromasin, also known as exemestane, after two or three years of tamoxifen. Results of studies showing the respective advantages of the three drugs are appearing in journals with regularity.
What is becoming more and more evident, according to a report by the American Society of Clinical Oncology (ASCO), a major U.S. group of cancer doctors, is that aromatase inhibitors belong somewhere in the first five years after primary therapy for breast cancer. It's the timing of when to use aromatase inhibitors that remains at issue. What is also not known yet is whether the three aromatase inhibitors are interchangeable.
"Optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen," said the ASCO report, which was issued in December, just before the five-year data on the big Arimidex (anastrozole) study were released in The Lancet. "Women with breast cancer and their physicians must weigh the risks and benefits of all therapeutic options."
Proponents for Arimidex believe the study of 9,366 women with localized breast cancer amounted to strong evidence that the best idea for many is to start with the aromatase inhibitor, foregoing tamoxifen entirely. "We now stick our necks out and say that anastrozole is the preferred initial treatment for postmenopausal women with hormone receptor-positive tumors," according to Baum. The study was the first to report five-year results.
Women taking anastrozole in the study, compared with those taking tamoxifen, had significant improvements in disease-free survival and time-to-recurrence. Overall, however, women taking anastozole didn't live longer than women taking tamoxifen.
The aromatase inhibitor also prevented some of the side effects, albeit rare, of tamoxifen. These include endometrial cancer, pulmonary embolism, and deep vein thrombosis.
In the Arimidex study, women taking the aromatase inhibitor had significantly fewer cases of endometrial than women taking tamoxifen. The same was true for other major side effects of tamoxifen. On the other hand, women taking tamoxifen had fewer bone fractures.
More information
Visit the American Society of Clinical Oncology (www.asco.org ) to view the assessment on aromatase inhibitors. 
SOURCES: Arimidex study, The Lancet, Jan. 1, 2005; Neil Love, M.D., Medical Oncologist and Editor, Breast Cancer Update, University of Miami (Fla.); Michael Baum, M.D., professor emeritus, University College, London; Massimo Cristofanilli, M.D., University of Texas M. D. Anderson Cancer Center, Houston; Debbie Saslow, Ph.D., director, breast and gynecologic cancer, American Cancer Society, Atlanta; Feb. 14, 2005, Cancer online
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