NIH Recommendations for Adjuvant Therapy

An important panel of breast cancer experts was recently convened at the National Institutes of Health (NIH). Their objective was to find some type of consensus on the best adjuvant therapies for treating breast cancer at its various stages.

From a patient's perspective, the word "adjuvant" is probably one of the most common-yet least understood-breast cancer terms. Simply put, "adjuvant therapy" means "additional therapy," or new treatments that are being given in addition to a primary treatment. Merriam Webster's Medical Dictionary defines adjuvant as "serving to aid or contribute," and "assisting in the prevention, treatment or cure of disease."

Currently, the primary treatment for localized breast cancer is either breast-conserving surgery (lumpectomy) and radiation, or mastectomy with or without breast reconstruction. Examples of adjuvant therapies beyond these primary treatments include chemotherapy, hormone therapy, and additional localized radiation therapy.

Dr. Patricia Eifel of the M.D. Anderson Cancer Center, the chairwoman of the NIH panel, reported on three of their major recommendations regarding adjuvant therapies for breast cancer:

• Most women with localized breast cancer should receive combination chemotherapy, which uses a number of different chemotherapies instead of just one drug. They should consider taking this combination treatment for three to six months after surgery to make sure any remaining cancer cells in their bodies are killed.
• The panel recommended that women whose breast cancer may have been stimulated by estrogen (estrogen-positive) should undergo adjuvant hormonal therapy for five years after surgery, regardless of their age. This typically involves taking the drug tamoxifen. However, the benefits of taking hormonal treatment longer than five years has not been established, they warned.
• The panel suggested that adjuvant radiation therapy-in addition to combination chemotherapy and/or hormonal therapy-could benefit women at high risk of recurrence. This includes women with evidence of cancer in at least four lymph nodes or with an advanced primary tumor, especially if a mastectomy was required. They cautioned, however, that the benefits of radiation for women with fewer than four positive lymph nodes are unknown.

The panel noted that a major limiting factor in identifying the best possible adjuvant therapies is the sparse participation by breast cancer patients in clinical trials, especially women over age 70. Eifel estimated that only 2 to 3 percent of women with breast cancer enroll in clinical trials.

And she called for continued research in certain important areas, including combined hormonal therapy, hormonal versus chemotherapy in premenopausal women, high-dose chemotherapy, and quality-of-life issues surrounding the side effects from combination chemotherapy.

Further Evidence

A month prior to the NIH consensus conference, similar findings were presented at the 2nd European Breast Cancer Conference in Brussels, Belgium. These showed that adjuvant treatments for breast cancer, including radiotherapy, chemotherapy, and, in particular the hormone treatment tamoxifen, prevent later recurrences of the disease.

Oxford's Sir Richard Peto presented the composite results of 300 randomized trials that included approximately 200,000 patients. "This is the first time we've had good evidence on the effects of treatment on 15-year survival," Peto said.

Peto noted that the use of such adjuvant therapies reduces relapses because they also directly target dormant disease. Therefore, he said, you not only get a benefit while you are currently receiving the adjuvant therapy, you also get an additional benefit accumulating in the 5 or 10 years after you've stopped. This is because of its impact on killing undetected microscopic cancer cells.

Peto also argued for the use of combination therapies, particularly hormonal therapy and chemotherapy. "If a woman has estrogen receptor-positive disease, then hormonal treatment works well," he said. "But so does chemotherapy. These aren't mutually exclusive. It's not a question of which is better ... one shouldn't let the use of one therapy preclude the use of the other."

Some Cautionary Findings

In contrast to the above findings about the benefits of adjuvant therapies, an article in the August 2000 issue of the Journal of Clinical Oncology reported that combining adjuvant radiotherapy with chemotherapy that includes the drug mitoxantrone may be associated with an increased risk of acute leukemia in women with breast cancer.

Dr. Claire Bonithon-Kopp of the University of Bourgogne in France and colleagues studied 3,093 French women who underwent surgery for breast cancer between 1982 and 1996. Almost 90 percent of the women also received adjuvant therapy, including radiotherapy alone (56.9 percent), or radiotherapy combined with chemotherapy (31.0 percent).

They found that women who did not did not receive any adjuvant therapy had a similar leukemia risk as the general population. However, women treated with adjuvant radiotherapy and chemotherapy had a higher overall risk. In particular, in women aged 64 and younger, chemotherapy with mitoxantrone was significantly associated with an increased risk of leukemia. But this increased risk was of only "borderline significance" in women older than 65.

"The risk of leukemia was found to progressively increase with cumulative doses of mitoxantrone," the researchers wrote. "This study provides some evidence that the increase in leukemia risk was mainly a result of the use of mitoxantrone."

Growing Options

In spite of the above finding regarding mitoxantrone, an overwhelming body of research supports the use of adjuvant therapies after the initial treatment for breast cancer. And, as promising research continues to progress, the treatment options available to breast cancer patients should increase dramatically in the coming years.

As Eifel said at the conclusion of the NIH consensus panel's deliberations, "The past ten years have contributed an enormous amount of new information about therapies that can be used to treat breast cancer after the initial surgery-so-called adjuvant therapies. This wide range of options requires that women and their physicians improve their communication to maximize treatment benefits."

SOURCES:
NIH Consensus Development Conference on Adjuvant Therapy for Breast Cancer, National Institutes of Health, November 1-3, 2000, Bethesda, Maryland
"Adjuvant Therapy for Breast Cancer," NIH Consensus Development Conference Statement #114, (http://odp.od.nih.gov/consensus/cons/114/114_statement.htm)
2nd European Breast Cancer Conference, October 2, 2000, Brussels, Belgium Journal of Clinical Oncology, August 2000; 18:2836-2842

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