Herceptin After Chemotherapy Helps Reduce Recurrence

Herceptin After Chemotherapy Reduces Recurrence in Women with Early-Stage, HER2-Positive Breast Cancer

M. Piccart-Gebhart et al., American Society of Clinical Oncology Annual Meeting, May 2005, late-breaking session

Is this for me? If your doctor has told you that you have early-stage, HER2-positive breast cancer and will need chemotherapy after surgery, you might want to read this article.

Background and importance of the study:Herceptin (chemical name: trastuzumab) works on breast cancers that make too much of the HER2/neu, or HER2, protein. These "HER2-positive" cancers tend to grow faster and are more likely to come back than breast cancers that are HER2-negative. About one out of every four breast cancers is HER2-positive.

Herceptin is approved by the U.S. Food and Drug Administration (FDA) for women with metastatic (advanced) HER2-positive breast cancer. The drug slows down or even stops the cancer's growth.

But new research has been done to see if Herceptin also helps women with early-stage disease. Studies presented at the 2005 ASCO annual meeting showed that Herceptin given at the same time as chemotherapy after surgery improved survival in women with early-stage, HER2-positive breast cancer. However, Herceptin may cause heart problems, and that's especially true when it's given at the same time as an anthracycline chemotherapy drug such as Adriamycin (chemical name: doxorubicin). In the study reviewed here, researchers wanted to know if giving Herceptin AFTER chemotherapy would benefit women with early-stage, HER2-positive breast cancer who had had surgery.

Study design: Sponsored by the Breast International Group (BIG), a nonprofit group of European breast cancer specialists, and F. Hoffman-La Roche Ltd., the makers of Herceptin, this study is known as the Herceptin Adjuvant Trial, or HERA Trial.

Nearly 5100 women from 39 countries with early-stage, HER2-positive breast cancer were in the study. The women all had either:

• breast-removing treatment (mastectomy) with axillary (underarm) lymph node dissection, or
• breast-conserving surgery (lumpectomy) with axillary lymph node dissection.

About 33% of the women were node-negative, which means no cancer cells were found in their lymph nodes.

All the women had completed a standard course of chemotherapy, either before or after surgery:

• About 70% had received an anthracycline chemotherapy drug such as Adriamycin (chemical name: doxorubicin).
• About 25% had received an anthracycline and a taxane, such as Taxotere (chemical name: docetaxel) or Taxol (chemical name: paclitaxel).
• About 5% had had chemotherapy without anthracyclines or taxanes.

Some of the women also had radiation therapy.

About 50% of the women had hormone-receptor-positive breast cancer. These women received hormonal therapy: tamoxifen, an aromatase inhibitor, or a luteinizing hormone-releasing hormone agonist.

The women were randomly assigned to one of three treatment groups after they completed chemotherapy:

• Herceptin every three weeks for one year,
• Herceptin every three weeks for two years, or
• no Herceptin and careful monitoring.

The researchers wanted to see if giving Herceptin AFTER chemotherapy would reduce the chance that the cancer would come back (recur).

Results: After only one year of follow-up, the researchers found that women taking Herceptin every three weeks had a 46% reduction in recurrence compared to women who did not get any Herceptin. Find out more about the HERA study. These results were statistically significant, meaning they were probably due to Herceptin and not just to chance.

Because these results were released early, after one year, the researchers were not able to compare outcomes of giving Herceptin for two years as opposed to one year. Also, these early results did not show a significant benefit in overall survival (how long women lived). But the researchers believe that the survival rates will improve as they follow the women over time.

Herceptin can cause heart problems. And Adriamycin, an anthracycline, when given in certain doses, has also been shown to be responsible for heart damage. Giving Herceptin with an anthracycline has been shown to increase the risk of heart problems. So the researchers looked carefully at any cardiac problems that developed.

About 0.5% of the women in this study who received Herceptin had congestive heart failure. This means that their hearts couldn't pump enough blood to their other organs. None of the women in the observation group had congestive heart failure.

Conclusions: The researchers concluded that giving Herceptin every three weeks for one year AFTER chemotherapy to women with early-stage, HER2-positive breast cancer significantly reduced recurrence. The chemotherapy and Herceptin were given after surgery with or without radiation.

The benefits of Herceptin don't appear to depend on the characteristics of the cancer. This means that Herceptin helped women with both hormone-receptor-positive and hormone-receptor-negative cancer, and women both with and without cancer cells in their lymph nodes.

Take-home message: Compared to chemotherapy alone, Herceptin AFTER chemotherapy lowers the risk of the cancer coming back for women with early-stage, HER2-positive breast cancer after surgery. This is one of the first research studies available on the use of Herceptin after surgery in women with early-stage (not advanced) breast cancer.

These early results on Herceptin are quite positive, especially when combined with the results of two other studies presented at the 2005 ASCO annual meeting: NSABP-B-31, a study by the National Surgical Adjuvant Breast and Bowel Project of 2,085 women, and NCCTG-N9831, a study by the North Central Cancer Treatment Group of 3,406 women.

The makers of Herceptin will soon ask the FDA to approve its use for women with early-stage breast cancer. The FDA will need to see the full results of the three studies, including information on all possible side effects, before granting approval. The FDA will closely evaluate any heart problems that appear to result from taking Herceptin.

The advance in breast cancer treatment reported here is especially important because HER2-positive breast cancer tends to be more aggressive than HER2-negative disease. Herceptin acts on the characteristic that makes HER2-positive cancer aggressive. Still, while the results are very positive and encouraging, it's important to keep in mind that these were EARLY results. The researchers plan to follow the women for several more years to look at their long-term survival and recurrence.

These three studies also bring up the question of the best way to give Herceptin: at the same time as chemotherapy (as in NSABP-B-31 and NCCTG-N9831) or immediately after chemotherapy (as in the HERA Trial).

The early results from NSABP-B-31 and NCCTG-N9831 show that Herceptin may boost the effects of chemotherapy. After three years of follow-up in those studies, the women had a 52% lower rate of recurrence, compared to a 46% reduction in the HERA Trial. Many doctors believe that giving Herceptin at the same time as chemotherapy will become the new treatment standard.

Researchers had been concerned that if Herceptin were given too close to anthracycline-based chemotherapy drugs, it might cause cardiac problems. Previous studies in which Herceptin was given at the same time as anthracyclines saw a dramatic increase in heart problems.

In the HERA Trial, only 0.5% of the women had heart problems. In NSABP-B-31 and NCCTG-N9831, women receiving Herceptin had a 3% to 4% increase in risk for congestive heart failure. Because all these results are preliminary, we don't know if any of these heart problems are reversible. More follow-up is needed to learn about long-term effects.

Meanwhile, you may be wondering if taking Herceptin now would help you:

• if you had early-stage, HER2-positive breast cancer and finished chemotherapy years ago: At this point, the value of Herceptin for you is unknown. Taking Herceptin even one or two years after chemotherapy hasn't been tested. As this research continues, breastcancer.org will continue to provide you with the most up-to-date information.
• if you have HER2-negative breast cancer: These results do not apply to you, because Herceptin is effective only against HER2-positive breast cancer.
• if you have HER2-positive, early-stage breast cancer that is either node-negative or node-positive and have had surgery: NSABP-B-31 and NCCTG-N9831 showed that Herceptin benefited women with HER2-positive, early-stage, node-POSITIVE cancer. The HERA Trial showed that Herceptin benefited women with HER2-positive, early-stage, node-NEGATIVE cancer (33% of the women in the study were node-negative). You and your doctor now may be considering chemotherapy, and you should seriously discuss the possible role of Herceptin. The discussion should include consideration of any cardiac risk factors you may have. Keep in mind that not all women need chemotherapy. In that situation, even if you are HER2-positive, it's unclear whether Herceptin would help you. No research has been done on giving Herceptin alone, without chemotherapy.

Remember that every woman reacts differently to treatment. It's very important to find the right combination that you're comfortable with and that works best for YOU.