High Levels of Immune Cells in HER2-Positive Tumors May Mean Herceptin Not Needed
A study suggests that HER2-positive breast cancers with high levels of tumor-infiltrating lymphocytes have a lower risk of recurrence when treated with chemotherapy alone compared to similar cancers treated with chemotherapy plus Herceptin.
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 differently to certain treatments than tumors with lower levels of the cells. So certain cancer patients might be able avoid certain treatments if they have higher levels of immune system cells in the cancer tumor.
A study suggests that HER2-positive breast cancer tumors with high levels of tumor-infiltrating lymphocytes had a lower risk of the cancer coming back (recurrence) when treated with chemotherapy alone compared to HER2-positive tumors with high levels of tumor-infiltrating lymphocytes treated with chemotherapy plus Herceptin (trastuzumab).
The study was published online by JAMA Oncology on Oct. 15, 2015. Read the abstract of “Association of Stromal Tumor-Infiltrating Lymphocytes With Recurrence-Free Survival in the N9831 Adjuvant Trial in Patients With Early-Stage HER2-Positive Breast Cancer.”
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 treatment with chemotherapy and/or Herceptin before or after surgery. Herceptin fights HER2-positive breast cancer by blocking the cancer cells’ ability to receive growth signals.
This study was an analysis of two groups of women who were part of the N9831 trial. All the women had been diagnosed with early-stage, HER2-positive breast cancer. The researchers measured the levels of tumor-infiltrating lymphocytes in each breast cancer. Tumors that were at least 60% infiltrated were considered to have high levels of tumor-infiltrating lymphocytes.
The women received one of two treatments:
- 489 women were treated with chemotherapy alone
- 456 women were treated with chemotherapy plus Herceptin
The chemotherapy regimen was Adriamycin (chemical name: doxorubicin) and Cytoxan (chemical name: cyclophosphamide) followed by weekly Taxol (chemical name: paclitaxel).
After about 4.4 years, the researchers looked at recurrence rates among the women. Overall, there were 162 recurrences: 8 in women with tumors with high levels of tumor-infiltrating lymphocytes and 154 in women with low levels of tumor-infiltrating lymphocytes. Looking at recurrence rates by treatment group and levels of tumor-infiltrating lymphocytes, the researchers found:
- 90.9% of the women who had cancers with high levels of tumor-infiltrating lymphocytes treated with chemotherapy alone had no recurrence
- 64.5% of the women who had low levels of tumor-infiltrating lymphocytes treated with chemotherapy alone had no recurrence
- 80% of the women who had cancers with high levels of tumor-infiltrating lymphocytes treated with chemotherapy followed by Herceptin had no recurrence
- 80.1% of the women who had cancers with low levels of tumor-infiltrating lymphocytes treated with chemotherapy followed by Herceptin had no recurrence
This means that early-stage, HER2-positie tumors with high levels of tumor-infiltrating lymphocytes had a better prognosis when they were treated chemotherapy alone than when they were treated with chemotherapy and Herceptin.
These results are completely different than the results from another study that suggested that early-stage, HER2-positive cancers with high levels of tumor-infiltrating lymphocytes had a better prognosis when treated with chemotherapy plus Herceptin.
Still, the researchers who did the study said there may not have been enough women diagnosed with tumors with high levels of tumor-infiltrating lymphocytes in the study. Only 94 women were classified as having tumors with high levels of tumor-infiltrating lymphocytes and only eight of these women had a recurrence. So it’s likely that the study couldn’t detect a benefit from Herceptin in this group of women because the numbers were too small.
The researchers also said that the cancer’s hormone-receptor status may affect levels of tumor-infiltrating lymphocytes.
This and other studies suggest that tumor-infiltrating lymphocyte cell levels may be a biomarker that can help doctors figure out which cancers may respond better to chemotherapy alone compared to chemotherapy plus Herceptin. Still, much more research is needed before doctors understand exactly how tumor-infiltrating lymphocytes may kill some of the cells in a cancer tumor 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.
— Last updated on July 31, 2022, 10:46 PM
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