Struggling for Earlier Detection, Better Treatment

In a ten-year period in the 1960's when 58,000 men and women died in the Vietnam War, 330,000 women in this country died of breast cancer.

This frightening statistic, presented by Nancy Brinker in her 1990 autobiography of one woman's struggle against breast cancer, brings home the staggering reality of the disease--a disease which remains second only to lung cancer as the major cause of cancer deaths in women.

The malady claims the lives of 46,000 women each year and drastically alters the lifestyles of 182,000 others who contract the disease. One in every nine women is predicted to develop breast cancer before the age of 85.

Scientists at Harvard and elsewhere have gained some insight into the mechanism of the disease, but while the five-year survival rate of women with breast cancer has risen from 78 percent in the 1940s to 93 percent today, the disease still baffles scientists who attempt to explain its origins, and a cure remains a distant goal.

In the vital struggle to design new strategies for fighting a disease about which few specifics are known, scientists have traditionally followed two routes of investigation: studying the causes and the actual mechanism of the disease, and working on developing treatments.

Researchers opting for the first path hope to devise an exact mechanism for the initiation and the growth of a tumor in the hope of blocking the process in its early phases.

Included in current lines of research are the analysis of varying stages of tumor development, ranging from genes present before the tumor is formed to the development of blood vessels which spur the growth of the tumor to the exact location and movement of the tumor.

Medical School Assistant Professor of Pediatrics Stephen H. Friend and his colleagues at the Massachusetts General Hospital (MGH) hope to find a definite genetic link to the development of breast cancer.

BRCA1, a gene believed to suppress tumor development, has recently been linked to breast cancer. Altered forms of BRCA1, which occur in one woman in 200, prevent it from functioning properly, and tumors can begin to grow. Another gene, p53, has also been determined to be a useful indicator of many cancers, including breast cancer.

According to Dr. Daniel F. Hayes, assistant professor of medicine at the Medical School and a medical oncologist at the Dana-Farber Cancer Institute, BRCA1 was the first gene to be "clearly associated as a cause of common malignancy."

"[Studying genetic predispositions for cancer] is clearly a worthwhile venture," Friend says. But he is quick to add that identifying an altered gene which may cause cancer does not necessarily enable doctors to prevent it from bringing on the deadly disease.

For the past five years, scientists have studied several different genes thought to be related to breast cancer. If several genes can be identified as positively correlated to breast cancer incidence, doctors can then screen women and identify those high-risk women who possess the genes before a tumor has actually formed.

Clinical studies involve developing better methods of screening women to determine whether or not a tumor is present and treating those who test positive accordingly.

Unfortunately, physicians are able to characterize only a fraction of breast cancer patients as belonging to the "high risk" category before a tumor is actually identified.

Approximately a quarter of breast cancer cases are associated with a family history of the disease or a hormonal abnormality. But the majority of patients lack characteristics which might have been considered precursors for breast cancer, leaving their risks undetectable.

Since it is difficult to predict who will develop a tumor, doctors must develop methods by which to identify a growth in its early stages. This identification is extremely important in determining the success of treatment.

Troyan said that the best means by which to detect a growth is by the mammogram, a process which accurately identifies 85 to 90 percent of tumors, coupled with a self exam.

According to Hayes, women who are routinely screened are 20 to 30 percent less likely to die as women who are not screened.

Many researchers say that current identification methods are not reliable enough, because they miss 10 to 15 percent of tumors. "We need to find even earlier detection methods, " says Troyan.

Medical School Assistant Professor of Pathology Ann. D. Thor also emphasized the need for early detection and characterization. "The most important thing is to diagnose it, to diagnose it right, and to diagnose it early," says Thor.

Researchers agree that screening should start as early as possible. But the question of how early tumors need to be identified is still up in the air, and some even question whether screening women under the age of 50 is beneficial.

Dr. Daniel B. Kopans, associate professor of radiology at the Medical School, argues that the disadvantage to early screening is the cost of biopsies on benign growths.

"If we screen women under the age of 50, at what age [do we screen], how often, and is there an absolute benefit?" he said.

On another venture to examine the development of tumors, Dr. M. Judah Folkman, Andrus professor of surgery at Children's Hospital and the Medical School, is concentrating on the formation of blood vessels, a process called angiogenesis.

Angiogenesis is directly linked to tumor growth, says Folkman, by the fact that growth is limited by a finite number of blood vessels. Until new blood vessels are formed, a tumor cannot increase dramatically in size.

But when a protein, called bFGF, releases a chemical signal which stimulates the growth of blood vessels, the tumor gains momentum and its cells proliferate, allowing it to enlarge.

Clinical studies currently underway measure both the number of blood vessels and the amount of bFGF which is necessary to "turn on" angiogenests. Scientists believe that high levels of blood vessels and protein will correlate with a higher incidence of breast cancer, allowing for another diagnostic device.

Epidemiological studies, those which collect cast amounts of data useful in predicting risks, are also utilized by some scientists to determine the causes of breast cancer. Dr. Susan I. Troyan, a breast surgeon and director of research at the Faulkner Hospital in Jamaica Plain, is one such researcher.

By gathering data describing both the nature of the tumor, its treatment and the lifestyle of the patient, doctors at the Faulkner hope to target non-biological factors which might correlate to an increased risk of contracting the disease.

Other breast cancer experts deal directly with breast cancer victims, in clinical trials which explore methods by which an already existing disease can be stopped in its tracks.

After the detection of a tumor, doctors must diagnose it to determine whether it is indeed cancerous and how far it has spread.

The best method of identification other than surgery is a biopsy, in which doctors actually remove a small piece of the tumor with a needle for analysis.

Scientists are working to fine-tune one method, known as fine needle aspiration biopsy, in which surgeons are guided to a tumor detectable only by mammogram.

Once a tumor has been identified as malignant and likely to spread, there are several routes of treatment available, according to Hayes.

Chemotherapy and radiation treatment are both widely used to attempt to destroy the tumor without surgery. Lumpectomy or mastectomy are alternative surgical methods to remove an advanced tumor.

Several drugs which seem to reduce recurrences are also being tested. Hayes cites taconite, an anti-estrogen drug, which has been demonstrated to reduce the likelihood of recurrent tumors, and taxol, a drug derived from Pacific yew trees which has been approved by the FDA for treatment of ovarian cancer and which may be a treatment for breast cancer.

All in all, substantial progress in both genetic and clinical breast cancer research and higher rates of survival have instilled confidence in researchers and also in patients whose lives are affected daily by the disease.

But experts in the field admit that medicine is far from having conquered breast cancer.

"It seems when you're in the field that there's very rapid progress," says Folkman. "There's a lot known, but you don't know if you know the right things...I don't think we know the key information yet."

Others are even less optimistic about progress to date. "We've just scratched the surface," says Norman L. Sadowsky, chief of radiology and director of the Faulkner-Sagoff Centre for breast health care. "In 25 years we'll look back and say 'they were really primitive in those days."