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TILs may predict response to trastuzumab
SAN ANTONIO — Higher levels of tumor-infiltrating lymphocytes predicted how women with HER-2–positive breast cancer responded to neoadjuvant treatment with chemotherapy and trastuzumab, according to study results presented at the San Antonio Breast Cancer Symposium.
The findings complement prior research that showed high levels of tumor-infiltrating lymphocytes (TILs) predicted response to adjuvant treatment with trastuzumab (Herceptin, Genentech) and chemotherapy, according to Sherene Loi, MD, PhD, medical oncologist and head of the Translational Breast Cancer Genomics Lab at the Peter MacCallum Cancer Centre in Melbourne, Australia.
Sherene Loi
“Levels of tumor-infiltrating lymphocytes may be a good biomarker of response to trastuzumab in primary breast cancer, something that researchers have been looking for with little success for some time,” Loi said.
In the GeparQuattro trial, Loi and colleagues examined breast tumor samples from 156 patients with operable or locally advanced HER-2–positive breast cancer who received chemotherapy and trastuzumab before surgery. These women were more likely to have a complete response defined by no residual invasive cancer detectable in the breast tissue and lymph nodes removed during the subsequent surgery.
Results showed each 10% increase in TILs was associated with higher rates of pathologic complete response (adjusted OR=1.16; 95% CI, 1.01-1.32) after neoadjuvant trastuzumab and chemotherapy.
Loi and colleagues also evaluated 202 HER-2–positive samples to try to better understand potential connections between TILs and gene expression levels of 13 pre-defined immune markers.
Gene expression analyses showed two of those markers — IDO1, which represents immunosuppression, and CXCL13, which represents chemoattractants — had the highest correlation with TILs.
Researchers determined no immune genes demonstrated a significant association with prognosis; however, ID01 and PD-1, which represents T-cell checkpoint receptors and ligands, were significantly associated with distant DFS benefit from trastuzumab (P=.029 for PD-1; P=.039 for IDO-1).
“The treatment interaction is positive for these two genes as a continuous variable, and it suggests that somehow trastuzumab is managing to change the balance of this tumor microenvironment and make it more favorable for the immune system,” Loi said during a press conference.
An evaluation of PD-1 and CTLA-4 reinforced that patients with high levels of these immunosuppressive genes responded well to trastuzumab, whereas patients with lower levels did not.
“Our study confirms that high levels of lymphocytic infiltration is significantly associated with high clinical benefit to trastuzumab when added to chemotherapy in newly diagnosed HER-2 disease,” she said. “These data suggest that trastuzumab acts not only directly on the tumor but can also help anti-tumor immunities.”
It remains unclear why some patients have TILs in their breast tumors at diagnosis and others do not, Loi said.
“We are actively investigating this and trying to understand why there is a positive relationship between tumor-infiltrating lymphocytes and better outcomes with trastuzumab therapy,” Loi said.
For more information:
Loi S. Abstract #S1-05. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
Disclosure: The study was funded by the European Union Seventh Framework Program RESPONSIFY project, the Breast Cancer Research Foundation and the Fonds J.C. Heuson. Loi reports no financial disclosures.