Herceptin Plus Chemotherapy Before Surgery Benefits Women with Early-Stage HER2-Positive Breast Cancer

Reviewed study: "Herceptin Plus Chemotherapy Before Surgery Benefits Women with Early-Stage HER2-Positive Breast Cancer" by A. Buzdar et al., Journal of Clinical Oncology, June 1, 2005 (published in advance on the Web on February 28, 2005)

Is this for me?: If you have stage I, II, or III HER2-positive breast cancer and need to have surgery, you might want to read this article.

Background and importance of the study:Herceptin is a drug designed to work against breast cancers that make too much of the HER2/neu, or HER2, protein. These cancers are called HER2-positive. They tend to grow faster and are generally more likely to recur (come back) than breast cancers that do not overproduce HER2. 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 (late-stage) HER2-positive breast cancer. The drug slows down or even stops the growth of the cancer.

Research studies have shown that Herceptin works better when it is combined with chemotherapy.

Because of the effectiveness of Herceptin and chemotherapy in treating late-stage HER2-positive breast cancer, researchers wondered if this combination treatment would also help women with early-stage HER2-positive breast cancer. In this case, they wondered if using Herceptin with chemotherapy BEFORE surgery would be helpful.

You may think of chemotherapy as something that happens AFTER surgery. But you may also receive chemotherapy before surgery to reduce the size of the cancer in the breast and to destroy cancer cells wherever they may be. If the breast cancer is reduced or even eliminated, then the surgery to remove any remaining cancer cells may be more successful. And if the cancer is smaller, you may be able to choose lumpectomy (breast-conserving surgery) and radiation instead of mastectomy (surgical removal of a breast).

In the study reviewed here, researchers compared Herceptin plus chemotherapy to chemotherapy alone before surgery in women with early-stage HER2-positive breast cancer. They wanted to see whether the combined therapy was more beneficial and whether it caused more side effects. In particular, Herceptin may cause heart problems, especially when given with anthracycline-type chemotherapy drugs, such as Adriamycin (chemical name: doxorubicin).

The study was first presented at the American Society of Clinical Oncology in 2004. breastcancer.org reported on the study in Research News in August 2004. Now, important new results from the study are available.

Also, look to Research News in June 2005 for a summary of two other new studies on the use of Herceptin and chemotherapy AFTER surgery. The new studies have results for more than 3,000 people with HER2-positive breast cancer and will be presented as the American Society of Clinical Oncology annual meeting in May 2005.

Study design: Researchers at the University of Texas M.D. Anderson Cancer Center in Houston studied 42 women with HER2-positive breast cancer. The women:

• ranged in age from 25 to 71,
• mostly had stage II cancer (4 had stage I, 28 had stage II, 9 had stage III, and 1 had stage IV),
• were split fairly evenly in terms of hormone (estrogen and progesterone) receptor status (24 were HR-positive and 18 were HR-negative), and
• were more likely to have cancer in their lymph nodes (24 women had lymph node involvement and 17 women did not).

The women were randomly split into two groups:

• One group (19 women) received four cycles (four "rounds") of paclitaxel (brand name: Taxol) followed by four cycles of FEC (fluorouracil, epirubicin, and cyclophosphamide).
• The other group (23 women) received the same chemotherapy, but also received weekly doses of Herceptin at the same time. The women received the treatments every week for 24 weeks.

The risk of heart side effects is higher when Herceptin is given together with anthracycline-type chemotherapy drugs. This group of medicines includes doxorubicin (brand name: Adriamycin) and epirubicin (brand name: Ellence). This study used epirubicin instead of doxorubicin, because it has been shown to be less harmful to the heart. The women in the study had cardiac check-ups before treatment began, after paclitaxel treatment was completed, after FEC was completed, and again during follow-up evaluations.

After the drug treatments were completed, all the women were evaluated. They then had either lumpectomy plus radiation therapy, or mastectomy. Pathologists (doctors who specialize in analyzing tissue specimens) evaluated the breast tissue removed during surgery to see how many women had a "pathologic complete response." That's when all traces of invasive cancer in the breast have disappeared.

After the surgery, women who were hormone-receptor-positive were put on tamoxifen if they were pre-menopausal or Arimidex (chemical name: anastrozole) if they were post-menopausal, in both cases for 5 years.

The researchers evaluated the women every four months for the first two years of follow-up and then every six months for the third year.

Results: After only 34 of the women in the study had completed treatment, the committee overseeing the research stopped the study. They did this because the women who had received chemotherapy plus Herceptin had dramatically better results than the women who had received only chemotherapy. The rate of disappearance of all invasive cancer in the breast was:

• 66.7% for women who received chemotherapy plus Herceptin, versus
• 25% for the women who received chemotherapy only.

The difference was statistically significant, meaning that it was likely due to the addition of Herceptin to the chemotherapy and not just to chance.

The researchers have revised the study and are continuing it. All women with HER2-positive breast cancer are being offered chemotherapy plus Herceptin.

None of the women in the study had congestive heart failure or other serious heart problems. A small number of women (five who received only chemotherapy and seven who received Herceptin plus chemotherapy) had a slight decrease (less than 10%) in the amount of blood pumped by the heart with each heartbeat. This amount returned to normal in follow-up evaluations.

Hormone receptor status didn't affect the benefits of chemotherapy plus Herceptin. In other words, hormone-receptor-positive AND hormone-receptor-negative cancers responded the same way to this treatment.

Conclusions: The researchers concluded that adding Herceptin to chemotherapy given before surgery benefits women with stage I, II, or III HER2-positive breast cancer. It didn't matter if the cancer was hormone-receptor-positive or hormone-receptor-negative. So far, treatment with Herceptin plus chemotherapy (with epirubicin) has not resulted in congestive heart failure or other serious heart problems.

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