Treatment given to weaken and destroy breast cancer BEFORE surgery is called neoadjuvant treatment. Neoadjuvant treatment isn't routinely used to treat early-stage breast cancer, but may be used if the cancer is large or aggressive. Neoadjuvant treatment is more commonly used before surgery for breast cancer that has spread outside the breast to other tissue in the breast area (locally advanced).
One or more chemotherapy medicines commonly are used for neoadjuvant treatment. When the cancer is HER2-positive, the targeted therapy Herceptin (chemical name: trastuzumab) may be added to the neoadjuvant regimen. Like Herceptin, Tykerb (chemical name: lapatinib) also targets HER2-positive cancers, so doctors wanted to see if it offered benefits as part of a neoadjuvant regimen for HER2-positive breast cancer.
Research results suggest that Herceptin is more effective than Tykerb in a neoadjuvant regimen for early-stage or locally advanced HER2-positive breast cancer. These results were presented at the 2010 San Antonio Breast Cancer Symposium (SABCS).
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 tend to be aggressive, so doctors may recommend neoadjuvant treatment for them. Herceptin and Tykerb work against HER2-positive breast cancers by blocking the cancer cells' ability to receive growth signals. Herceptin is given intravenously. Tykerb is a pill taken by mouth.
In this study, called the GeparQuinto trial, 620 women diagnosed with early-stage or locally advanced HER2-positive breast cancer got a neoadjuvant regimen of:
- Cytoxan (chemical name: cyclophosphamide)
- Ellence (chemical name: epirubicin)
followed by Taxtotere (chemical name: docetaxel).
Half of the women got Herceptin as part of the neoadjuvant regimen and the other half got Tykerb.
After the neoadjuvant treatment was done, the women had surgery to remove the cancer. The researchers recorded how many women had no active cancer cells in the tissue removed during surgery. When there are no cancer cells in the tissue removed, doctors call it a "pathologic complete response." Some doctors believe a pathologic complete response to neoadjuvant treatment means the cancer is less likely to come back (recurrence).
A pathologic complete response was much more likely in the women who got the neoadjuvant regimen that included Herceptin (45%) compared to the women who got Tykerb (29.9%).
Herceptin offered more benefits than Tykerb even when the researchers more strictly defined complete pathologic response as no active invasive cancer cells AND no active non-invasive cancer cells:
- 31.3% of women who got neoadjuvant Herceptin had pathologic complete response
- 21.7% of women who got neoadjuvant Tykerb had pathologic complete response
Neoadjuvant treatment can shrink the cancer. A smaller cancer can make lumpectomy a good alternative to mastectomy when mastectomy would have been recommended without neoadjuvant treatment. In this study, women who got neoadjuvant Herceptin were more likely to have lumpectomy instead of mastectomy (65.6%) compared to women who got Tykerb (56%).
Diarrhea, sometimes severe, can be a side effect of both Herceptin and Tykerb. Diarrhea also can be a side effect of chemotherapy. In this study, 6.9% of the women had severe diarrhea. Severe diarrhea was more common among women who got Tykerb.
A number of women in both treatment groups stopped taking Herceptin or Tykerb or stopped the entire neoadjuvant regimen because of serious side effects, including severe diarrhea. Stopping treatment was more common in women who got Tykerb. This may partly explain why women who got Tykerb were less likely to have a pathologic complete response to neoadjuvant treatment.
- 16% of women in the Tykerb group stopped both chemotherapy and Tykerb compared to 10% of women in the Herceptin group
- 7% of women in the Tykerb group stopped Tykerb but continued on chemotherapy compared to 3.1% of women in the Herceptin group
When the researchers saw that more women in the Tykerb group were stopping treatment, they lowered the Tykerb dose for women who joined the study later. All the women were advised to take Imodium (chemical name: lopermide), an anti-diarrhea medicine, if diarrhea developed.
Chemotherapy and targeted therapies can cause low white blood cell counts (called neutropenia, which increases the risk of serious infection). About 82% of the women in this study had severe neutropenia. When the researchers saw how common neutropenia was, they required the women to take a medicine to boost white blood cell production. These types of medicines are called granulocyte colony stimulating factors. Neulasta (chemical name: pegfilgrastim) and Neupogen (chemical name: filgrastim) are two examples.
These results suggest that if only one anti-HER2 medicine is used as part of a neoadjuvant regimen for HER2-positive breast cancer, Herceptin may be a better choice than Tykerb. Still, experts hope that more research will offer more information on how best to use anti-HER2 medicines alone, together, or in sequence, both before and after surgery. Another study, called Neo-ALTTO, found that complete pathologic response was more likely when BOTH Herceptin and Tykerb (instead of either alone) were used in a neoadjuvant regimen for early-stage or locally advanced HER2-positive breast cancer.
If you've recently been diagnosed with HER2-positive breast cancer and haven't had surgery yet, you may want to ask your doctor about this study and if neoadjuvant treatment makes sense for you.