Doctors are on the hunt for biological targets that could help them produce a breast cancer vaccine.

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Forty years ago, women who had abnormal results on a Pap smear often wound up with a hysterectomy. Doctors removed their uterus because they had no other way to prevent women from developing cervical cancer, researcher Susan Love says.

Today, she says, doctors can prevent cervical cancer with a vaccine.

That has led some to ask: Could researchers develop a vaccine against breast cancer?

At first glance, the notion seems impossible.

Vaccines are typically developed only after researchers have a clear target, such as a virus or bacteria. Scientists don't even know what causes most breast cancers.

But researchers do know it's possible for viruses to cause cancer, says James Gulley, a researcher at the National Cancer Institute who has worked on vaccines to treat prostate cancer.

HPV causes not only cervical tumors, but cancers of the head and neck, as well as the vulva, vagina, penis and anus. Hepatitis B can cause liver cancer, Gulley says. The Epstein-Barr virus can lead to at least three types of lymphomas.

Another virus, called HMTV, or human mammary tumor virus, has been found in 40% of breast tumors. HMTV seems particularly common in a rare but often deadly form of breast cancer, called inflammatory breast cancer, according to a 2010 study inCancer.

Scientists don't know if HMTV caused those cancers or was simply along for the ride.

At this point, doctors say they have more questions than answers about the role infections might play in breast cancer.

Breast cancer advocates — tired of seeing women beaten down and burned by toxic treatments — are eager for a game-changer.

"We're not going to get very far unless we ask those big questions," says Fran Visco, president of the National Breast Cancer Coalition. As a country, the USA focuses "the vast majority of research dollars on the next treatment for breast cancer. But we only see incremental benefits from all of these treatment drugs."

Looking at drugs in the pipeline, Visco says, "there's nothing on the horizon that could have a major impact on breast cancer. We don't want to continue to just creep along."

That's why the National Breast Cancer Coalition has organized a vaccine initiative called the Artemis Project. Seed grants will allow researchers to scour breast cancer genomes — the tumors' entire collection of genes — to look for infectious microbes.

The Avon Foundation for Women has committed $6 million to learning whether infections contribute to breast cancer. Scientists will study 1,000 breast cancer samples whose genomes have been sequenced, looking for signs of viruses or bacteria.

Doctors from the Cleveland Clinic are taking a slightly different approach to developing a preventive vaccine, focusing on a protein expressed on cancer cells, but not healthy tissue, except during lactation. This research is in some of the earliest stages, and has been tested only on mice.

Other scientists are taking a related approach, testing treatment vaccines designed to prevent tumors from metastasizing, or spreading, to other organs, a condition that is fatal.

Doctors at the University of Pennsylvania, for example, are targeting HER2+ breast tumors, whose cells have lots of copies of a protein called HER2.

They've begun testing personalized cancer vaccines, made with women's own immune cells. Doctors are testing the vaccines in women with DCIS, or ductal carcinoma in situ, a very early breast cancer or precancer.

Doctors vaccinate these women after surgeons have removed their tumors, hoping the vaccine will prevent their cancers from coming back.

Women will have to wait years to know if their vaccine has worked, because relapses often occur many years after diagnosis.

Targeting proteins on cancer cells is difficult, because cancers arise from the body's own cells, Gulley says. Scientists have to be careful to find a protein that is found on cancer cells but not healthy cells, to avoid causing a dangerous autoimmune reaction.

However daunting the task, Love says, scientists need to find more ways to prevent breast cancer.

"When Angelina Jolie learns she has a breast cancer gene, we don't know what else to do, so we cut her breasts off," says Love, president of the Dr. Susan Love Research Foundation. "We have to be looking for the cause. I worry that we don't, that we're paying too much attention to the treatment, which comes with a huge cost."

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