Several weeks ago, Sandy Rovner's Healthtalk column Jan. 9 focused in large part on Rose Kushner's theories regarding the "indiscriminate" use of adjuvant chemotherapy in breast cancer patients. The article neither explained the rationale for adjuvant chemotherapy nor bothered to mention numerous scientific studies that support its use.
Anticancer drugs administered to women shortly after breast cancer surgery are known as adjuvant chemotherapy. They are given to patients who have no evidence of cancer cells outside of the affected breast and adjacent lymph glands, and their use is considered standard practice by medical oncologists (cancer specialists).
The use of adjuvant chemotheraphy is based on our knowledge that an undetectable amount of cancer cells are frequently scattered throughout the body at the time breast cancer is diagnosed. Those cells are responsible for recurrences of the cancer five and even 10 years later. Adjuvant chemotherapy is used in an attempt to wipe out those cells before they multiply and become more resistant to any form of therapy.
For decades the predominant therapy for breast cancer was the radical mastectomy, the draconian removal of the breast and surrounding tissues, often followed with radiation therapy. More recently, the treatment of breast cancer has changed to include:
* Less mutilating operations such as the modified radical mastectomy and the lumpectomy followed by radiation.
* The recognition that the prognosis for women with breast cancer depends on several factors, including the size of the cancer and the number of lymph glands that contain cancer cells.
The discovery that breast cancer cells, especially in older women, will frequently regress when exposed to certain hormones.
Overall, approximately 75 percent of the women with axillary lymph nodes under their arms positive for cancer will develop recurrent cancer within 10 years of their initial diagnosis. This rate has not appreciably changed in 40 years.
The use of adjuvant anticancer drugs began in 1957, when the National Surgical Adjuvant Breast Project (NSABP) began the first of three large-scale trials to compare chemotherapy and surgery to surgery alone over a 20-year period. In the first trial, using a single anticancer agent, there seemed to be some advantage to the chemotherapy group within the first five years, but that benefit evaporated in subsequent years.
In the second study, a stronger dose of a second chemotherapy agent was administered and younger patients showed a marked improvement in "disease-free survival," the length of time between diagnosis and recurrence. However, older women had a less clear-cut advantage.
In a third trial a combination of two anticancer drugs seemed more effective than one drug alone.
Finally, in the best known and most quoted study, Dr. Gianni Bonadonna in Milan compared a group of patients receiving three chemotherapy agents in moderate doses with those who received no treatment immediately following mastectomy. The trial ended in 1975 and showed that the chemotherapy treated group had a 64 percent "disease-free survival" after five years, compared with 48 percent in the untreated group.
Initially, there seemed to be little or no benefit from the adjuvant chemotherapy for women past menopause. However, a reanalysis of the data showed a benefit for older women as long as they had received greater than 85 percent of the prescribed dosages of the chemotherapy agents. More recently, another study showed that a five-drug adjuvant drug combination was more effective than the standard three-drug regimen.
The drugs most commonly used in adjuvant chemotherapy at this time include cyclophosphamide, methotrexate and 5-fluorouricil. The side effects can include nausea, vomiting, hair loss, anemia and decreased defense against infection. All are completely reversible upon discontinuation of the drugs. In general, most women taking adjuvant chemotherapy are able to maintain a nearly normal activity level.
The long-term effects of adjuvant chemotherapy for breast cancer are unknown. The drug combinations in use today have not been associated with leukemia or other dreaded complications, but surveillance of patients who participated in adjuvant studies is continuing.
The judgment regarding adjuvant therapy has been complicated by the discovery that hormonal therapy can stabilize and even shrink breast cancer cells throughout the body. The big advantage to hormonal therapy is its minimal side effects and its efficacy in treating older women past menopause whose cancers have hormone receptors. Its drawback is ineffectiveness in treating many younger women whose cancers do not contain hormone receptors.
Whether or not hormonal agents such as tamoxifen or megestrol will add to the therapeutic benefit of adjuvant chemotherapy is currently under study.
In summary, adjuvant chemotherapy is a valuable, relatively new tool for improving our therapy for breast cancer. Its use has been validated in multiple studies and is based on the need to kill the microscopic amounts of cancer cells that have already spread at the time of breast surgery in most women.
When adjuvant chemotherapy is administered by physicians with expertise in its use, side effects are usually tolerable and permit the patient to lead a nearly normal life style.
Everyone looks forward to the time when therapy for breast cancer will be more effective and less toxic. For the present, adjuvant chemotherapy represents the best method for stacking the odds in favor of a life without recurrent cancer.
Robert S. Siegel is an assistant professor of medicine and medical director of the Oncology Unit at the George Washington University Medical Center.
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