BREAST CANCER: FIGHTING BACK : Search for New, High-Powered Weapons : Growing understanding of the disease and biological approaches under study may eventually lead to preventive solutions as alternative treatments.

TIMES STAFF WRITER

Breast cancer is not an invader. It's a traitor.

Your own cells, misled by faulty genes, multiply and spread out of control, eventually crowding out the normal cells you need to stay alive.

Over the past two decades, methods of treating breast cancer have been refined, but the basic approach remains unchanged: surgery to remove the cancer, then X-ray radiation or chemicals to mop up surviving cancer cells. There is still no way of knowing whether you got them all.

"We really haven't gotten very far from slash, burn and poison," says Susan M. Love, director of the Revlon/UCLA Breast Center. "The treatments are still pretty grim. The newer biological approaches are where the answers are."

Researchers are studying antibodies grown in mice and adapted for humans that interfere with the cancer cells' growth cycle. Scientists hope the antibodies will be able to kill a tumor and hunt down stray cancer cells, perhaps eliminating the need for both surgery and follow-up radiation and chemotherapy.

Tamoxifen, a drug used to treat breast cancer since the 1970s, is now being tested as a possible cancer prevention drug in healthy but cancer-prone women. A Vitamin A derivative is also being tested that might increase Tamoxifen's effectiveness.

"My prediction is these trials are going to work, and I think that's fabulous," says Marc Lippman, director of the Lombari Cancer Center at Georgetown University. "And I think there will be better agents out there too."

From 1973 to 1990, the rate of death from breast cancer in the United States varied hardly at all. During that time, about one in every 3,700 women died from the disease each year.

Lately there have been improvements. Deaths were down nearly 5% between 1989 and 1992, probably due to the refinement of standard treatment techniques, researchers say.

"If you optimally treat women today with so-called 'nasty' chemotherapy, fully a quarter of the patients that would have died don't die," Lippman says. "That's not trivial. That's a significant advance.

"If you get lung cancer, you'll die of it. Diagnosis and death are virtually synonymous. But with breast cancer, fewer than 25% die. A long time ago it used to be half."

New and potentially more effective avenues of attack on cancer are coming from recent discoveries of cancer-causing gene defects within human cells. They can be either inherited from parents, developed in response to something in the environment or appear as spontaneous mutations.

Dennis J. Slamon, director of the Revlon/UCLA Women's Cancer Research Program, says research is concentrating on two broad classes of genes, those that promote cell growth and those that suppress it.

There are a large number of these genes, perhaps as many as 100, and they are scattered on different chromosomes. Each gene may have scores of different cancer-promoting defects. While that makes research difficult, it also makes the spread of cancer difficult.

"Probably for almost all cancers, it takes more than one gene alteration. Think about it: If it didn't, if it were easy for cancer to spread, we'd be in big trouble," Slamon says.

Instead, it takes a chain of genetic events over 10, 20, perhaps 30 years for cancer to develop, says Patricia A. Ganz, director of cancer prevention and control research at UCLA's Jonsson Comprehensive Cancer Center.

"If we can find ways to slow that development, we won't have those cancers to treat," she says.

How Cancer Attacks

A human body produces new cells by the billions every day. An elaborate and only partially understood system of chemical signals among cells tells each when more cells are needed and when that's enough.

When you cut your finger, cell reproduction is accelerated to heal the wound, and when it's healed, the signal to stop is issued. But if the stop signal is not issued--or if it is not recognized by some cells--cell division continues. Those extra cells form a tumor.

Not all tumors are cancerous; some are just nuisances. But breast cancer tumors are life-threatening because their defective genes give them the green light to divide at a much faster rate, and the green light never turns red.

They no longer act in concert with normal cells. They are on their own, obeying and replicating their own outlaw genes. They multiply, expand their boundaries and create their own blood vessels for nourishment. Now the normal cells have competition for the body's life-sustaining resources, a contest the normal cells will eventually lose if the cancer goes unchecked.

Typically, breast cancer cells begin growing somewhere in the breast's lobules, where milk is created, or in the ducts, which carry milk to the nipple. It only takes one cancer cell to break through the lobule or duct wall and begin a tumor in the breast's fat and surrounding tissues.

Before long, cancer cells have broken off from the main group and entered the lymph or blood circulation system. There they are recognized as criminals and attacked by the immune system, which can take care of them without much trouble.

Until, that is, there are so many cancer cells that the immune system is overwhelmed. At some point, cancer cells escape and attach to other body parts, where they start new tumors.

Different cancer cells are attracted to different tissues. Breast cancer cells tend to spread to the lungs, liver and bones, where the cancer cells eventually hog so much of the body's nutrients or crowd out so much of a vital organ that the person dies.

Seeking Antibodies

"Humanized" mouse antibodies being tested by Slamon and others cannot enter the cancer cells and so do not directly attack the genes causing the cancer's growth.

Instead the antibodies remain outside and in effect jam the gene's communications network.

The gene produces molecules called receptors on the outside of cells that act as antennas, waiting to receive chemical signals to start or stop cell division. The antibodies attach themselves to these antennas, blocking any further communication.

Because these kinds of tumors seem utterly dependent on their communication system, "we think we'll be able to effectively kill the tumor cells," Slamon says.

While only about 30% of breast cancer comes from this particular gene defect, success "would serve as an example on how other cancers might be treated," Slamon says.

The study began at UCLA in 1991 and has spread to 85 institutions. Phase One showed that the antibodies are safe, Phase Two that they are effective against cancer cells, Slamon says. The final phase, now underway, is a test of effectiveness using a larger pool of women.

Results are probably two to three years away, Slamon says.

Tamoxifen Trials

First used as a not-too-effective fertility drug, Tamoxifen was enlisted as a cancer weapon after researchers noticed it inhibited the growth of breast cancer cells. Clinical trials showed that in women who had been treated for breast cancer, Tamoxifen prevented recurrence of the disease.

It turned out Tamoxifen reduced the risk of cancer recurrence by reducing the estrogen level in the bloodstream and blocking its absorption in the breast. It seemed to stimulate the immune system as well, another cancer-fighting advantage.

As an unexpected bonus, Tamoxifen seemed to duplicate the advantages of post-menopausal estrogen therapy by reducing the risk of heart disease and osteoporosis, which makes bones weak and brittle.

But the downside was significant. Tamoxifen appeared to increase the risk of uterine cancer just as estrogen does.

A national study began in 1992 to test whether Tamoxifen could prevent cancer as well as treat it. Researchers have recruited 11,000 women considered to be at high risk for breast cancer and are seeking 5,000 more. Some receive Tamoxifen, some a placebo. (Women wanting to join the study should call [800] 422-6237.)

Ganz at the UCLA cancer center, one of the more than 200 institutions participating in the trial, says it will be five to seven years before conclusions can be drawn.

"If it works, the average woman won't take Tamoxifen, but women at high risk may have very substantial benefits," Ganz says.

Radiation Therapy

After a cancerous lump is removed, doctors decide whether they think the cancer is limited to the breast. If so, they usually prescribe radiation therapy only--repeated low doses of X-rays shot through the breast in hopes of mortally wounding remaining cancer cells.

It works because cancer cells are more vulnerable to radiation than normal cells. But it's risky because too much radiation can cause cancer in healthy cells. Research continues into how to target the one and only nick the other.

Beryl McCormick, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, is launching experiments in computer-controlled radiation, which promises to greatly increase radiation marksmanship. By shaping the X-ray beam to the three-dimensional shape of the treatment area, adjoining normal tissues can be spared.

"The effect is protection of the normal organs and the possible ability to deliver higher doses to the cancer cells," she says.

General use of these techniques are probably two years away, McCormick says.

Chemotherapy

Like McCormick, Richard Elledge, a chemotherapy specialist at the University of Texas Health Center San Antonio, wants to be able to use higher doses of his particular weapon.

Physicians turn to chemotherapy when they fear cancer cells have spread to other parts of the body. A series of the cancer-killing chemicals is introduced into the bloodstream over a period of weeks to circulate and destroy cancer cells wherever they are.

As in radiation, the hope is to wipe out cancer cells without doing too much damage to normal cells. But the patient still takes a beating, often suffering hair loss, nausea, fatigue, diarrhea and a loss of white blood cells that can lower resistance to infection.

Elledge says the research in chemotherapy is concentrating on better chemicals that have less effect on normal cells and on medications that treat side effects. Effective anti-nausea drugs are becoming available, and more are coming, he says. Methods to extract, then replace, blood cells after a bout of chemotherapy are helping the body restore natural immunity faster and therefore permitting increased doses.

"We've come a long way, but we're very far from where we want to be," Elledge says.

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DETECTION

Mammography, while not infallible, is at present the most effective method for detecting breast cancer.

In addition to mammograms and regular checkups, the American Cancer Society encourages women to do routine, monthly self-exams for unusual lumps or changes in their breasts.

* Beginning at age 20:

Breast self-examination every month, clinical breast examination every three years.

* Beginning at age 40:

Breast self-examination monthly, clinical breast examination annually. Mammography every one to two years.

* Beginning at age 50:

Breast self-examination monthly, clinical breast examination annually. Mammography annually.

SELF-EXAMINATION

POSITIONS

Standing: Visual inspection of contour, shape and skin.

Side-lying position: Lie on opposite side of the breast to be examined. This position allows women with larger breasts to most effectively examine outer half of breast.

Flat position: Lie flat on back with a pillow under the shoulder of the breast to be examined. This position may be the only one necessary for women with small breasts.

MOTION AND AREA

Make continuous, dime-sized circles with fingers. Most breast cancers occur in the upper, outer area of the breast. Varying levels of pressure should be used to examine the full thickness.

PATTERN

Use one of these patterns to cover entire area:

Vertical strips: Make palpations in strips a finger's-width apart.

Wedge: Use a pattern like the spokes of a wheel. Examine each segment, moving from outside toward nipple.

Circle: Make a full circle around perimeter. Repeat smaller and smaller rings until you reach the nipple.

IS IT CANCER?

Finding a lump on your breast does not mean you have cancer, only that you might. If you find a lump, have a doctor check it. Of lumps judged serious enough to test, 80% are harmless.

What Is Not Breast Cancer

Lumpiness. Normal in many breasts. A tumor is one, dominant lump, usually grape-sized.

Cysts. Fluid-filled sacs like interior blisters.

Fibroadenomas. Smooth, hard, round lumps that need not be removed. Most common in teen-agers.

Pseudo-lumps. Exaggerated lumpiness, a protruding rib, hardened implanted silicone or dead fat tissue after surgery.

Nipple discharge. Rarely indicates cancer.

What Might Be Cancer

A lump, usually painless, sometimes under the arm.

Thickening of the breast.

A change in breast density.

Redness or dimpling of skin.

Eczema rash on the nipple.

A shadow on a breast X-ray.

Indications of Probable Spread of the Breast Cancer

A large tumor, more than two inches.

Swollen skin near a tumor.

A tumor that has broken through the skin.

A tumor stuck to the chest muscles.

* Sources: American Cancer Society; "Dr. Susan Love's Breast Book" (second edition).

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Cancer Cell Growth

Cancer cells grow a unpredictable rates--some very slow, some very rapidly. If the average doubling time for a cancer cell is 100 days, as researcher J. Gershon-Cohen found when he tracked cells, it often takes years for a cancerous growth to become large enough to be detected. A centimeter's worth of cancer-- the size at which it can first be felt contains100 billion cells. If a cancer grew at a predictable rate, doubling every 100 days, it would take as long as 10 years to reach that size.

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