One of the scientific presentations at a recent National Institutes of Health conference on breast cancer went largely unnoticed by the public but has caused considerable excitement among researchers.
Indeed, it offers genuine promise for identifying some high-risk patients who might respond to more aggressive therapy even when currently used tests suggest otherwise. And, on the other hand, the new test described in the presentation might spare some patients from having to undergo possibly unnecessary cytotoxic chemotherapy with its unpleasant side effects and attendant psychological pain.
The presentation by Dr. John S. Meyer, chief pathologist at St. Luke's Hospital in Chesterfield, Mo., described a test that marks the genetic material from the cancer cell biopsy to determine how fast the cell is growing -- how fast, in other words, the cancer is growing.
Meyer presented preliminary evidence that the test, which measures cell activity, or kinetics, could target patients at high risk for eventual recurrence even though there was no other evidence of cancer spread, even in the nearby lymph nodes. It might also identify patients for whom there is an extremely good chance that the cancer will spread, and for whom especially aggressive therapy might help if initiated immediately.
Even at its best, the outlook for breast cancer victims, taken as a whole, is not wonderful.
True, the years between the initial onset of the disease -- or group of diseases, as some think -- and its almost inevitable eventual recurrence have been stretched, and for some patients that probably translates into long-term survival. But for too many, the future is murky at best.
The recent NIH consensus conference identified some of the best current choices for treating breast cancer, including cytotoxic chemotherapy in premenopausal patients and hormonal therapy for some women who were past menopause. But even these conclusions were controversial and conceded by the panel to be less than ideal.
The group of breast cancer patients with the best prognosis are women whose tumors are small and have not spread to the lymph nodes under the arm. Of these women, 65 to 80 percent will be alive in 10 years. That also means, however, that up to one third of them will not be alive in 10 years.
It is this latter group, the ones more likely to die within 10 years, that might be identified by Meyer's test, so that they, and not the others, could receive aggressive treatment early.
Changes in the primary treatment of breast cancer have offered incalculable advantages to the breast cancer patient. The switch from the routine use of the Halsted radical mastectomy to either modified mastectomy or breast-sparing surgery represents findings that the newer techniques offer no less survival advantage, but nor do they confer more.
All of these findings have been teased out over the years from results of clinical trials -- groups of similarly aged patients with the same types of tumors and medical outlooks, randomly divided between two or more sets of treatments, known in the business as "treatment arms."
The outcomes of the patients in the various groups are compared during and after the treatment and eventually analyzed statistically to determine whether one treatment is better than the other.
In the absence of a phenomenal and almost self-evident breakthrough -- a polio vaccine, for example -- testing in clinical trials is the only system medical science has for demonstrating that one approach is better than another.
In breast cancer, with its capricious and chronic nature, clinical trials are are virtually the only way to know which treatment works best. And it is also true that oncologists in private practice, as knowledgable as most of them are, do not yet have the confirmed scientific findings -- they do not yet exist -- to know for sure which patients should get which treatments, for how long, in what amounts and in what combinations. Yet only 3 percent of American women with breast cancer participate in such research.
Indeed, the single most telling presentation before the NIH panel was a statistical overview by British biostatistician Richard Peto.
Peto, who was somehow able to lend drama as well as credence to his charts and figures, arrived at his conclusions after some months of comparing and combining trials from almost all over the world.
Modest but statistically significant differences between types of therapy became evident in Peto's overview, whereas they had been undetectable or conflicting in small individual trials. It was in the overview, for example, that the anti-estrogen hormone Tamoxifen was seen to be effective in a group of postmenopausal women.
As strongly as it could, the consensus panel urged breast cancer patients, their surgeons and their oncologists to participate in clinical trials.
Most participants agreed. But there is a basic conflict between doctors, who want to give what they believe is the "best" treatment to their individual patients, and scientists, who want to know for sure what the best treatments are.
John Meyer is certain that the test he has been working with for nearly a decade can make a genuine contribution to the treatment of breast cancer. It will, however, require much more testing to prove its usefulness.
The test, called thymidine labeling index (TLI), adds the nucleic acid thymidine, made slightly radioactive, to a culture of growing can- "cer cells. After a week of growth, the radioactively labeled thymidine is incorporated into the DNA of newly produced cancer cells. The researcher can then use a special process to count the number of new cancer cells.
The test produces a ratio of labeled to unlabeled cells, which indicates the number of new cancer cells. The higher the ratio, the faster that form of the cancer is growing.
Meyer's findings suggest several things, including:
*Large breast cancer size suggests rapid growth of the tumor, not necessarily neglect.
*Because high TLI rates occur in other cancers (lymphomas, certain testicular cancers) that can be successfully controlled with cytotoxic chemotherapy, high TLI breast tumors may respond as well.
Cancer cells, by and large, are more dangerous when they proliferate rapidly, in part because they can mutate faster into strains that are resistant to any known therapy. But, notes Meyer, they are also more vulnerable when they are dividng so fast.
*Hormone therapy (such as Tamoxifen) seems to work best when the tumor has a low TLI index -- which means it is slow growing.
The TLI results may designate fast growing tumors when the hormone tests are positive or negative, or when the axillary nodes are positive or negative. It is an independent test of the tumor's virulence.
"What is exciting about this," says National Cancer Institute biochemist Barbara Vonderhaar "is that it offers an objective test of the tumor. When a biopsy is taken, the pathologist stains it with various dyes and compounds and can determine by its shape if it is abnormal. This can be pretty subjec-tive. So far, the most common objective test is whether the cancer is responsive to the hormones estrogen and progesterone, but this is not 100 percent satisfactory.
"This test can take us into a second or third dimension of defining the tumor."
TLI is being tested in Italy, says Meyer, and some results are scheduled to be published soon.
"But," he says, "the next step is to find out whether you can first identify the high risk patients and, next, whether you can prevent relapse by treating them with a chemotherapeutic regimen."
With a randomized study, Meyer says, "you can find out if you are preventing recurrences and then the advance can save lives. But if you never do that, some people will be using it and others won't because they won't be convinced it works."
Trials done by the National Surgical Adjuvant Project for Breast Cancers, headed by Dr. Bernard Fisher, Meyer said, "really established a firm basis and revolutionized surgical treatment, but they were done over the objections of people who thought they knew what was best. And it turns out they really didn't know at all."
For more information about NIH-sponsored clinical trials, call 636-5700 in the metropolitian area or 1-800-4-CANCER.