By William J. Cromie

Gazette Staff

Genetic research, effective screening tests, and advances in knowledge about the progression of cancer are leading to better ways to handle the disease, according to Harvard scientists. Along with experts from other institutions, they are making encouraging assessments of how the dread epidemic might be brought under control.

The researchers presented their evidence and opinions at a meeting called "Cancer in the New Millennium," held in New York City on Tuesday.

Understanding the relationships between tumor genes and normal genes, they agree, is a key to more accurate prediction of tumor behavior and, eventually, to more effective treatment.

David Livingston, Emil Frei Professor of Medicine at the Dana-Farber Cancer Institute, compared each cell in the body to an enormous jigsaw puzzle. "In a cancer cell," he said, "some of the pieces do not fit, because of distortions of shape, size, or both."

Each piece, fitting or distorted, is a product of the action of one or more genes. Knowledge of how tumor and host genes interact can be translated into sound predictions of tumor-cell behavior, which in turn can guide the choice of effective anti-tumor treatment.

Livingston noted some of the "nonscientific hurdles" in the way of taking advantage of this new information. "Among them," he said, "are the innate fear of the knowledge of abnormal genes by many people and the need to ensure absolute patient confidentiality to those undergoing genetic analysis."

He recommended that people should not have their genes screened for predisposition to cancer unless they can take part in a suitable trial designed to prevent that cancer.

Detection vs. Treatment

Even without widespread use of genetic testing, "the fight against cancer seems to have turned the corner," noted James Talcott, assistant professor of medicine at Dana-Farber Cancer Institute. "For the first time, comprehensive surveys indicate a small but steady decline in cancer death rates over the period from 1990 to 1995. These improvements have resulted from advances in cancer prevention, early detection, and treatment."

As an example, he cited progress in prevention and non-genetic screening. Pap smears "have dramatically lowered the incidence of cervical cancers," he said. "Similarly, mammography is effective in detecting early and curable breast cancer and in lowering death rates."

Talcott, along with Bruce Chabner, professor of medicine, and Frank Haluska, assistant professor of medicine, both at Massachusetts General Hospital, published their views in yesterday's Journal of the American Medical Association, as did other speakers at the millennium meeting. "The challenge now is to assure that all women, both insured and uninsured, have access to screening," they wrote. They also recommended yearly tests for blood in the stool, which lead to early detection of polyps and tumors and reduce death rates of colon cancer by 15 to 30 percent.

The researchers were not as enthusiastic about colonoscopy, examination of the inside of the colon with a long, flexible viewing device. The latter is expensive and its effectiveness in decreasing death rates hasn't been proven. However, it is a good idea for those with family members who have the disease and those carrying genes known to predispose one to colon cancer.

On the negative side, the Harvard researchers noted that chest X-rays and sputum examinations have not proved effective for reducing the toll of lung cancer.

And blood tests for prostate specific antigen (PSA) as a detector of prostate cancer remain questionable. "The value of detecting and treating early prostate cancer is clouded by the tumor's uncertain impact on survival and quality of life," Talcott said.

Deaths due to prostate cancer have not increased despite its sharply rising incidence. Also, it's not clear that the frequent side-effects of treatment -- impotence and incontinence -- are balanced by benefits to the patient. Many men with slow-growing tumors die with prostate cancer, rather than of it.

Most specialists recommend yearly PSA testing starting at age 50. The two groups at highest risk for prostate cancer -- black men and those with a family history of the disease -- should discuss earlier testing with their doctors.

Deadly Skin Cancer

Talcott, Chabner, and Haluska urged everyone, particularly summer sun lovers, to stay on the alert for signs of melanoma, a deadly skin cancer. Its incidence is growing rapidly in the U.S. New cases are doubling each year, rising to 40,300 last year, with 7,300 deaths. The increase is not due to better detection methods, say researchers, but to increased exposure to the sun.

Early detection carries a special urgency, Talcott warned. Early stages of melanoma can be cured, but the cure is directly related to the size of the dark moles on the skin from which melanomas grow.

A new way to determine the risk of melanoma by the number and size of moles was described by Wallace Clark, visiting professor of pathology at the Medical School and his colleagues from the National Cancer Institute, the University of Pennsylvania, and the University of California, San Francisco.

According to their scale, those with a substantial number of small moles have about double the risk of melanoma compared to those with few moles. An increased number of small and normal moles, 50 or more, quadruples the risk. Having one abnormal mole doubles the risk; 10 or more abnormal moles raises the risk 12-fold. Abnormal moles are flat, 0.2 inches or larger, and may be variable in color, irregular in shape, and asymmetric in outline.

"Physicians having responsibility for patient examination may now add routine, careful examination of the entire skin as an additional procedure for cancer prevention and mortality control," Clark said. "Careful and widespread study of the number and nature of a person's moles should result in substantial decline in [deaths] due to melanoma. Finally, the research goes far beyond melanoma, for it puts a complete model of cancer in women and men on their most visible organ, their skin. Here, it can be studied in all of its manifestations and more of cancer's secrets may be expected to be revealed."