The Food and Drug Administration (FDA) has approved the first novel targeted therapy for use in early-stage HER2-positive breast cancers. The drug, trastuzumab (Herceptin), offers hope of a cancer-free future to the thousands of women diagnosed worldwide each year with HER2-positive breast tumors. Herceptin previously was approved only for women with advanced (metastatic) HER2-positive breast cancer.

Edith Perez, M.D., director of Mayo Clinic's Breast Clinic in Jacksonville, Fla., led one of the four pivotal studies that proved the benefit of Herceptin in early-stage disease. Here Dr. Perez explains how Herceptin works and who might be a candidate for targeted therapy.

It's a group of breast cancers in which HER2 — a protein called human epidermal growth factor receptor 2 — spurs the growth of new cancer cells. HER2 stimulates a cell to divide, and while a little on a cell is normal, a lot is not. HER2-positive breast cancers carry extra copies of the HER2 gene. Experts aren't sure exactly why HER2-positive tumors make too much of this protein, but when this happens, the cancer becomes more aggressive. Only about 20 percent to 30 percent of breast cancers are HER2-positive.

Compared with HER2-negative breast cancers, HER2-positive cancers respond less well to standard adjuvant therapy — chemotherapy, hormone therapy or a combination of both — so women with this type of cancer have a high risk of their cancer returning (recurrence) and of their dying from it.

When you have a biopsy or breast cancer surgery, your tumor is tested for biological markers. During a laboratory test known as immunohistochemical analysis, the amount of HER2 protein in the tumor is measured. Results are measured on a scale from 0 (negative) to 3+ (strongly positive). A score of 3+ indicates a high likelihood that Herceptin treatment will help you. Scores of 0 to 1+ mean that you're unlikely to benefit from Herceptin treatment. A score of 2+ tells your doctor that another test is needed to determine whether Herceptin treatment will be good for you. This test is called fluorescence in situ hybridization (FISH), and it helps determine how many copies of the HER2 gene your tumor cells carry.

Ask your doctor what your biopsy samples will be tested for. Make sure that any testing for biological markers is done at a central or reference laboratory that's experienced in testing for the HER2 gene. Increased rates of false-positive results — test results indicate positive when they're actually negative — are more likely to occur at a less experienced testing facility. A false-positive test may result in your receiving therapies that couldn't possibly help you, while excluding you from treatments that could.

Herceptin is a specific type of biological therapy, a monoclonal antibody, designed to shut down activity of HER2 proteins by attaching to them and, in effect, smothering them. This halts the pro-growth molecular instructions that these proteins relay into the bodies of cancer cells.

This type of therapy is often referred to as "targeted therapy" because the drug zeroes in on cancer cells much more closely than chemotherapy drugs do, thereby sparing surrounding tissue. Clinical trials have shown that Herceptin targeted therapy reduces the risk of recurrence by about half in early-stage HER2-positive breast cancer.

No, Herceptin doesn't replace other adjuvant therapies. In the clinical trials that examined Herceptin use for early-stage HER2-positive breast cancer, Herceptin was used in conjunction with adjuvant chemotherapy and whatever anti-estrogen hormone therapy or radiation treatments were recommended to the women in the trials. There's no evidence right now to suggest that Herceptin should be given alone as the only adjuvant therapy a woman with HER2-positive breast cancer receives.

Until recently, Herceptin was approved only for use in women with metastatic, or advanced, HER2-positive breast cancer. Carefully designed clinical trials looked into the possibility that Herceptin might benefit women with early-stage HER2-positive breast cancer. Data from these clinical trials showed that Herceptin can indeed be of benefit to such women, so the drug manufacturer submitted an application to the FDA to approve Herceptin for the early-stage indication as well. After a period of review, the FDA granted the approval. The decision broadens the availability of the drug to more women with early-stage HER2-positive breast cancers.

Because it's not a cell-destroying chemotherapy drug, Herceptin doesn't bring about the same side effects as chemotherapy drugs do, such as nausea and vomiting, hair loss, and increased risk of infection. And Herceptin is not an anti-estrogen treatment, so it doesn't cause side effects related to the lowering of estrogen levels, such as bone thinning or hot flashes. However, Herceptin does increase your risk of congestive heart failure. Although this risk is low, clinical trials to date don't provide long-term outcomes, so it's possible this risk could increase over time. Your doctor would need to follow you for any signs or symptoms of congestive heart failure.

Herceptin is administered (infused) directly into your bloodstream, similar to how you may have received chemotherapy drugs. The first dose of Herceptin usually takes about 90 minutes to administer. You'll be closely monitored for any adverse side effects. Thereafter, smaller maintenance doses are given over a 30-minute period.

Studies are ongoing, but the results to date from clinical trials show that treatment with Herceptin for one year reduces the risk of cancer recurrence or death by about half.

Even before Herceptin got FDA approval for use as adjuvant therapy, your doctor could prescribe it for you if you met the criteria. This is called off-label use. With FDA approval, though, the drug is more likely to be covered under your health insurance and will become standard therapy.