The National Cancer Institute on Wednesday reinforced the controversial "clinical alert" it issued last May which suggested that many women with early breast cancer could benefit from chemotherapy following initial treatment.
"Increasing use of this form of therapy . . . is going to make a difference in the lives of thousands of patients," Dr. Samuel Broder, director of the cancer institute, told a press conference.
Institute officials said that in the nine months since the alert was issued, many physicians have adopted procedures reflecting the new information.
The prognosis for women whose cancer has not spread to the underarm lymph nodes has always been relatively favorable. Until recently, the standard treatment has been mastectomy--removal of the breast--or lumpectomy, removal of the tumor only, followed by radiation treatments.
Now, three studies sponsored by the cancer institute and a new, fourth international study based in Switzerland--all reported in this week's New England Journal of Medicine--have found that women with unaffected lymph nodes who receive chemotherapy after primary treatment are less likely to suffer a recurrence of the disease in the next three to four years than women who did not receive the drugs after having either a mastectomy or a lumpectomy with radiation.
Findings Spurred Alert
The results of the three institute-sponsored studies last spring became the basis of a highly unusual clinical alert that was sent to about 13,000 cancer specialists and cancer organizations nationwide. Public release of the findings represented a dramatic departure from the usual practice of publishing such reports in a respected medical or scientific journal after peer review. The publication process, however, often takes many months.
"We can't necessarily wait for a publication to come out when we feel there is information that women--or men, or children--need to have," Broder said.
Institute officials said that after the clinical alert last spring, they queried 11,850 physicians about its impact on their treatment procedures. Approximately 75% of them said they had changed their method of treating women with node-negative breast cancer in accordance with the new findings, the officials said.
An estimated 142,000 women every year are found to have invasive breast cancer, or cancer that has affected adjacent breast tissues. About 70,000 of these women will be found to have so-called "node-negative" cancer, that is, cancer that has not yet reached the lymph nodes under the arms.
"We used to believe that breast cancer spread in an orderly fashion, from the breast to adjacent lymph nodes, and then to other parts of the body," said Dr. Bernard Fisher, breast cancer specialist at the University of Pittsburgh and chairman of the National Surgical Adjuvant Breast and Bowel Project.
Cancer Cells Scattered
"We thought that if the cancer had not spread to the nodes it was unlikely to have reached other parts of the body, but now we understand . . . that cancer cells may have traveled to distant parts of the body, where they can remain hidden until they cause illness years later. These scattered cancer cells can only be reached by systemic treatments, such as hormonal manipulation and chemotherapy."
Of the 70,000 women who are found to have node-negative breast cancer every year, 30% or more ultimately may suffer a recurrence of the disease, the institute said, and recurrence is "usually associated with a fatal outcome." The newly published studies found that adjuvant chemotherapy or hormonal therapy "can significantly reduce the rate of recurrences and increase the number of these patients who are free of breast cancer several years after primary treatment," the institute said.
About 43,000 women will die of breast cancer this year, according to the institute's estimate.
"The extended disease-free survival we have found in these studies is itself an important benefit," Broder said. "Hopefully, it will also translate into a long-term survival benefit."
In an editorial in the same issue of the Journal, however, Dr. William L. McGuire of the University of Texas Health Science Center at San Antonio warned that if doctors used chemotherapy to treat all women with node-negative breast cancer, it would prevent recurrence for about 5,040 of the estimated 70,000 patients.
Toxic Effects Noted
Meanwhile, he said, the others will have been treated needlessly at a cost of $338 million, and perhaps 100 of them could die from the treatment itself. Also, he said, many women will suffer from the drugs' toxic side effects. These can include increased susceptibility to infection, mouth sores, nausea, vomiting and diarrhea due to reduction of the white blood cell count.
"I would argue that the cost considerably outweighs the benefits of treating all node-negative patients, especially in the absence of a proved survival benefit," McGuire wrote.
In another editorial, Dr. Vincent T. DeVita Jr. of Memorial Sloan-Kettering Cancer Center in New York, the former director of the cancer institute who headed the agency at the time the clinical alert was issued, said that the studies show "an impressive reduction in the risk of recurrence." DeVita urged that the drugs be offered to all breast cancer patients except those with very small tumors.
The studies did not cover women with non-invasive tumors, and the American research did not include women with microscopic tumors. Thus, researchers said, the information is insufficient as to whether chemotherapy might also be beneficial for them. New studies are being designed to address these categories of patients, they said.
Recurrence Rate Cut
In the institute-sponsored studies, the additional proportion of patients who remained disease-free after three to four years because of adjuvant chemotherapy ranged from 6% to 15% overall, although some categories of patients benefited more than others, the institute said. In all of the trials, it said, "there was a significant benefit in the group that received adjuvant therapy compared to the group that did not receive it."
The institute said that it is too early to detect a difference in overall survival rates between the two groups. Overall survival refers to all patients still living, regardless of whether their disease has recurred. Disease-free survival, on the other hand, counts only those who have had no recurrence.
"There have been few deaths in either group so far, but improved survival of patients who received adjuvant therapy may become apparent after more time has elapsed," the institute said.