Pathologic Complete Response to Targeted Therapy Treatment Before Surgery Linked to Better Outcomes for HER2-Positive, Early-Stage Disease

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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 disease).

One or more chemotherapy medicines are commonly used in a neoadjuvant treatment regimen, including Taxol (chemical name: paclitaxel). The targeted therapies Herceptin (chemical name: trastuzumab) and Tykerb (chemical name: lapatinib) also may be used in a neoadjuvant regimen if the cancer is HER2-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 tend to be aggressive, so doctors may recommend neoadjuvant treatment for them. Herceptin and Tykerb fight 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.

One way for doctors to judge the effectiveness of neoadjuvant treatment is to look at the tissue removed during surgery to see if any active cancer cells are present. If no active cancer cells are present, doctors call it a “pathologic complete response.” Doctors have wondered if a pathologic complete response after neoadjuvant treatment is linked to better outcomes for early-stage, HER2-positive breast cancer.

The latest results from an ongoing study suggest that pathologic complete response after neoadjuvant Herceptin and Tykerb for early-stage, HER2-positive, hormone-receptor-negative breast cancer is linked to better outcomes.

The research, “The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06),” was presented on Dec. 11, 2013 at the 2013 San Antonio Breast Cancer Symposium by Martine Piccart-Gebhart, M.D., Ph.D., associate professor of oncology at the Universite Libre de Bruxelles and head of the Department of Medicine at the Jules Bordet Institute in Brussels, Belgium. Dr. Piccart-Gebhart is a member of the Breastcancer.org Professional Advisory Board.

Dr. Piccart-Gebhart is the lead researcher of the NeoALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) study.

In the NeoALLTO study, 455 women diagnosed with early-stage or locally advanced HER2-positive breast cancer were randomly assigned to get one of three treatment regimens before surgery:

  • Herceptin (149 women)
  • Tykerb (154 women)
  • Herceptin and Tykerb (152 women)

The targeted therapies were given alone for 6 weeks and then the women received Taxol for 12 more weeks.

After the 18 weeks of treatment were done, the women had surgery to remove the cancer. The researchers recorded how many women had a pathologic complete response to the neoadjuvant treatment. The researchers plan to follow the women for 10 years after neoadjuvant treatment to look at the relationship between pathologic complete response and outcomes.

After surgery, all the women also got three cycles of FEC chemotherapy followed by 34 weeks of the same targeted therapy regimen they got before surgery. The FEC chemotherapy regimen is made up of fluorouracil, Ellence (chemical name: epirubicin), and Cytoxan (chemical name: cyclophosphamide).

In this first analysis looking at 3 years of follow-up, the results showed that women who got both Herceptin and Tykerb before surgery were more likely to have a pathologic complete response than women who got only Herceptin or only Tykerb:

  • 51% of the women who got the combination of Herceptin and Tykerb had a pathologic complete response
  • about 25% of the women who got only Tykerb or only Herceptin had a pathologic complete response

Women who had a pathologic complete response to treatment before surgery had a lower risk of the cancer growing or coming back (recurrence), as well as a lower risk of dying from cancer or any other cause:

  • 86% of the women who had a pathologic complete response had no recurrence or second primary cancer compared to 72% of the women who didn’t have a pathologic complete response
  • 94% of the women who had a pathologic complete response were alive after 3 years, with or without the cancer coming back (overall survival), compared to 87% of the women who didn’t have a pathologic complete response

The link between pathologic complete response and better outcomes was strongest in women diagnosed with HER2-positive, hormone-receptor-negative breast cancer. Still, the researchers were only looking at 3 years of follow-up. HER2-positive, hormone-receptor-positive breast cancers may be more diverse than HER2-positive, hormone-receptor-negative cancers and may take longer to recur. As more years of follow-up information is collected, researchers may find a link between pathologic complete response and outcomes in HER2-positive, hormone-receptor-positive breast cancer.

Both Herceptin and Tykerb can cause side effects, some of them serious. Women who got the combination of Herceptin and Tykerb before surgery had about the same side effects as women who got only Tykerb. These two groups had more severe side effects than women who got only Herceptin. The most common side effects were diarrhea, liver problems, and rash. Although heart problems can be side effect of both Herceptin and Tykerb, heart problems weren’t a major side effect in the study.

If you’ve recently been diagnosed with HER2-positive, hormone-receptor-negative breast cancer and haven’t had surgery yet, you might want to talk to your doctor about this study and ask if treatment with Herceptin and Tykerb before surgery makes sense for you.

More research is being done that will help doctors understand how to best use these targeted therapies in combination before and after surgery. The ALTTO study, which is related to the NeoALLTO study, is looking at the best way to use Herceptin and Tykerb after surgery to treat HER2-positive breast cancer.

Stay tuned to Breastcancer.org for updates on both the NeoALLTO and ALLTO studies.


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