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Experimental Medicine Plus Standard Chemotherapy Helps Treat HER2-Positive, Hormone-Receptor-Negative Disease

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A study has found that the experimental targeted therapy neratinib plus a standard chemotherapy regimen before surgery for HER2-positive, hormone-receptor-negative disease offers more benefits than the standard chemotherapy regimen alone before surgery.

The study was presented at the American Association for Cancer Research 2014 Annual Meeting in April. Read the abstract of “Neratinib plus standard neoadjuvant therapy for high-risk breast cancer: Efficacy results from the I-SPY 2 Trial.”

Treatment given to weaken and destroy breast cancer cells before surgery is called neoadjuvant treatment.

Hormone-receptor-negative breast cancers don’t have receptors for the hormones estrogen or progesterone. Hormone-receptor-negative breast cancers are usually more aggressive, harder to treat, and more likely to come back (recur) than cancers that are hormone-receptor-positive.

HER2-positive breast cancers have too many copies of the HER2/neu gene, which make too much of the HER2 protein. HER2-positive breast cancers also tend to be aggressive, so doctors may recommend neoadjuvant treatment for them.

Neratinib is a type of targeted therapy medicine called an irreversible pan-HER inhibitor. Neratinib fights HER2-positive breast cancer by blocking the cancer cells’ ability to receive growth signals. Neratinib is a pill taken by mouth.

In this study, called I-SPY 2, researchers looked at 194 women diagnosed with HER2-positive, hormone-receptor-negative breast cancer. The women were randomly assigned to get one of two treatments before surgery:

  • 116 women got neratinib plus Taxol (chemical name: paclitaxel) followed by a combination of Adriamycin (chemical name: doxorubicin) and Cytoxan (chemical name: cyclophosphamide)
  • 78 women got only Taxol followed by Adriamycin and Cytoxan

After chemotherapy, the women had surgery to remove the breast cancer. A pathologist examined the removed tissue to see if there were signs of cancer cell activity. One way doctors judge the effectiveness of treatment given before surgery is to look at the tissue removed during surgery to see if any active cancer cells are present. If no active cancer cells are there, doctors call it a “pathologic complete response.” Many doctors believe that a pathologic complete response to neoadjuvant treatment means the cancer is less likely to come back.

In addition to looking at whether neratinib plus standard chemotherapy helped treat breast cancer before surgery, the I-SPY 2 study also is interesting because it uses a new and different type of study design. The researchers used what they call an “adaptive algorithm” to see which types of breast cancer responded the best to the different regimens as the study went on. In other words, the study saw how different types of breast cancer responded to the treatments and then assigned more women diagnosed with cancers likely to respond to the treatment to that treatment arm.

When a treatment arm added enough people, that treatment “graduated” to a larger, later phase trial. The goal of the study’s design is to figure out more quickly which types of breast cancer respond to experimental treatments and then get the treatments approved and to market more quickly and efficiently.

This round of results from the I-SPY 2 trial suggest that the combination of neratinib plus Taxol followed by Adriamycin and Cytoxan before surgery is better than Taxol followed by Adriamycin and Cytoxan alone for HER2-positive, hormone-receptor-negative breast cancer. This was based on the pathologic complete response rates:

  • 56% of women diagnosed with HER2-positive, hormone-receptor-negative breast cancer had a pathologic complete response rate to neratinib plus Taxol followed by Adriamycin and Cytoxan
  • 33% of women diagnosed with HER2-positive, hormone-receptor-negative breast cancer had a pathologic complete response rate to Taxol followed by Adriamycin and Cytoxan

Like any medicine, neratinib can cause side effects. In this study, many of the women treated with neratinib had severe diarrhea.

Based on these positive results, the researchers recommended that the neratinib-Taxol-Adriamycin-Cytoxan regimen before surgery for HER-positive, hormone-receptor-negative breast cancer be put into a phase III trial. Phase III trials compare the safety and effectiveness of a new treatment to the current standard of care. Phase III trials are large and are the last step a new treatment goes through before the FDA considers approving it for general use.

If you’ve been diagnosed with HER2-positive, hormone-receptor-negative breast cancer and are planning your treatment before surgery, you might want to talk to your doctor about this study. Ask your doctor if neoadjuvant chemotherapy makes sense for you based on your unique situation. If you’re willing to participate in a clinical trial, you may have the option of being treated with the neratinib-Taxol-Adriamycin-Cytoxan chemotherapy regimen. Talk to your doctor about clinical trials that might be a good fit for you. You can visit the Clinical Trials pages for more information.

And stay tuned to’s Research News for the latest information on new treatments for breast cancer.

Editor’s Note: On July 17, 2017, the U.S. Food and Drug Administration approved Nerlynx (chemical name: neratinib) to treat early-stage, HER2-positive breast cancer for an extended period after surgery in people who have previously been treated with Herceptin (chemical name: trastuzumab).

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