High Levels of Immune Cells in Breast Tumors May Predict How Cancers Respond to Treatments

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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.

Two recent studies suggest that breast cancer tumors with high levels of tumor-infiltrating lymphocytes respond better to certain treatments, including the targeted therapy Herceptin (chemical name: trastuzumab) and carboplatin, a chemotherapy medicine.

The two studies are: “Tumor infiltrating lymphocytes (TILs) indicate trastuzumab benefit in early-stage HER2-positive breast cancer (HER2+ BC)” and “Increased tumor-associated lymphocytes predict benefit from addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer in the GeparSixto trial (GBG 66).” The studies were presented on Dec. 11, 2013 at the 2013 San Antonio Breast Cancer Symposium.

In the first study, researchers looked at breast cancer tissue samples from 445 women diagnosed with early-stage, HER2-positive breast cancer and identified 156 women with breast cancer that had high levels of tumor-infiltrating lymphocytes. All the women had been treated with Herceptin and chemotherapy before surgery (doctors call treatment given before surgery neoadjuvant treatment).

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 fights HER2-positive breast cancer by blocking the cancer cells’ ability to receive growth signals.

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.”

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.

For every 10% increase in the number of tumor-infiltrating lymphocytes, there was a 16% increase in the number of women who had a pathologic complete response.

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

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.

In the second study, researchers found a similar relationship between tumor-infiltrating lymphocytes and breast cancer response to carboplatin.

Carboplatin is platinum-based chemotherapy. It weakens or destroys breast cancer cells by damaging the genetic material in the cells and making it hard for cells to repair any genetic damage.

The researchers analyzed tissue samples from 588 women diagnosed with early-stage HER2-positive or early-stage triple-negative breast cancer. They found that about one-quarter (24.7%) had high levels of tumor-infiltrating lymphocytes.

Triple-negative breast cancer is breast cancer that is estrogen-receptor-negative, progesterone-receptor-negative, and HER2-negative. About 10-20% of breast cancers -- more than one out of every 10 -- are triple-negative. Triple-negative disease tends to be more aggressive than other types of breast cancer.

The women in the study all received neoadjuvant treatment. Women diagnosed with HER2-positive disease were treated with a combination of doxorubicin and a taxane, as well as Herceptin and Tykerb (chemical name: lapatinib). Half the women also received carboplatin. Women diagnosed with triple-negative disease were treated with the doxorubin-taxane combination, as well as Avastin (chemical name: bevacizumab). Half the women also got carboplatin.

When the researchers analyzed the tissue removed during surgery, they found that overall 60.3% of the women with cancer with high levels of tumor-infiltrating lymphocytes had a pathologic complete response compared to 35.8% of women with cancer with low levels of tumor-infiltrating lymphocytes.

The tumor-infiltrating lymphocytes seemed to have more of an effect on tumors treated with carboplatin. In women who weren’t treated with carboplatin:

  • 46.6% of women with cancer with high levels of tumor-infiltrating lymphocytes and 33.5% of women with cancer with low levels of tumor-infiltrating lymphocytes had a pathologic complete response

In women who were treated with carboplatin:

  • 75% of women with cancer with high levels of tumor-infiltrating lymphocytes and 38.1% of women with cancer with low levels of tumor-infiltrating lymphocytes had a pathologic complete response

This result happened in both types of breast cancer. In women diagnosed with triple-negative breast cancer treated with carboplatin:

  • 76.2% of women with cancer with high levels of tumor-infiltrating lymphocytes and 52.2% of women with cancer with low levels of tumor-infiltrating lymphocytes had a pathologic complete response

In women diagnosed with HER2-positive breast cancer treated with carboplatin:

  • 73.1% of women with high levels of tumor-infiltrating lymphocytes and 22.9% of women with cancer with low levels of tumor-infiltrating lymphocytes had a pathologic complete response

“This is the year where the impact of the immune system in breast cancer is coming to reality with the interest in immunomodulation therapies,” said Edith Perez, M.D., professor of medicine at the Mayo Clinic Jacksonville and member of the Breastcancer.org Professional Advisory Board. “These presentations clearly show that we need to pay attention to tumor-infiltrating lymphocytes because this factor may predict prognosis in breast cancer and may also show that it may be important in the prediction of benefits of different therapies in breast cancer.”

While researchers believe that tumor-infiltrating lymphocytes may kill some of the cells in a cancer tumor, more research is needed before doctors understand exactly how this process works and why some cancers have more tumor-infiltrating lymphocytes than others.

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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