Immune Cells in Early-Stage, HER2-Positive Breast Cancer Cells Linked to Better Response to Treatment Before Surgery

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Tumor-infiltrating lymphocytes are white blood cells that have left the bloodstream and moved into a cancer tumor. White blood cells are immune cells made by your bone marrow to help your body fight infection.

Researchers have wondered if cancer tumors that have higher levels of these immune system cells might respond better to treatments than tumors with lower levels of the cells and so give patients better outcomes and a better prognosis.

Earlier research has found that HER2-positive, early-stage breast cancer tumors that have higher levels of tumor-infiltrating lymphocytes respond better to Herceptin (chemical name: trastuzumab) given after surgery. Doctors call treatments given after surgery adjuvant treatments.

In this study, called the NeoALTTO trial (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization), researchers wanted to know if higher levels of tumor-infiltrating lymphocytes in early-stage, HER2-positive breast cancer tumors could be linked to a better response to Herceptin or Tykerb (chemical name: lapatinib) given before surgery.

The results suggest that there is an association between higher levels of tumor-infiltrating lymphocytes and a better response.

The study was published online on April 30, 2015 by JAMA Oncology. Read “Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial.”

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.

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.”

In the NeoALTTO study, 455 women diagnosed with HER2-positive, early-stage breast cancer were randomly assigned to one of three neoadjuvant treatment regimens:

  • Herceptin for 6 weeks, followed by weekly Taxol for 12 weeks
  • Tykerb for 6 weeks, followed by weekly Taxol for 12 weeks
  • a combination of Herceptin and Tykerb for 6 weeks, followed by weekly Taxol for 12 weeks

After the neoadjuvant treatment was done, the women had surgery to remove the cancer.

All the women had three cycles of fluorouracil, Ellence (chemical name: epirubicin), and Cytoxan (chemical name: cyclophosphamide) after surgery. This chemotherapy combination is commonly called CEF.

The researchers found that nearly half (47.4%) of the women with cancers that had high levels of tumor-infiltrating lymphocytes had a pathologic complete response to the neoadjuvant treatment. Overall, less than a third (31.7%) of all the women in the study had a pathologic complete response.

Levels of tumor-infiltrating lymphocytes in the cancer tumors ranged from 5% to 30%. Cancer tumors that had tumor-infiltrating lymphocyte levels higher than 5% were more likely to have a higher pathologic complete response rate, no matter which neoadjuvant treatment they received.

Every 1% increase in the number of tumor-infiltrating lymphocytes was linked to a 3% decrease in the risk that the cancer would come back (recur) or spread. Again, this wasn’t affected by the type of neoadjuvant treatment.

The results suggest that the immune system can affect breast cancer outcomes as well as influence how the cancer responds to Herceptin and Tykerb.

Still, the researchers aren’t sure why some women have high levels of tumor-infiltrating lymphocytes in a breast cancer tumor and others don’t. They plan to do more research to figure out which proteins may influence the behavior of the lymphocytes.

Stayed tuned to Breastcancer.org for the latest information on tumor-infiltrating lymphocytes and how they may affect breast cancer outcomes.



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