Marker in HER2-Positive Breast Cancer Linked to Chemo Benefit

The level of stromal tumor-infiltrating lymphocytes (Str-TILs) may influence which treatment is the most effective in women with HER2-positive breast cancer.

The level of stromal tumor-infiltrating lymphocytes (Str-TILs) may influence which treatment is the most effective in women with HER2-positive breast cancer, according to a study presented at the 2014 San Antonio Breast Cancer Symposium.

Edith Perez, MD, deputy director at large for the Mayo Clinic Cancer Center and the Serene M. and Frances C. Durling professor at Mayo Clinic College of Medicine, Jacksonville, Florida, presented results of a study that showed that women with HER2-positive breast cancer who had high levels of Str-TILs had a decreased risk for recurrence after treatment with chemotherapy alone compared with women with low levels of TILs.

“These results suggest that levels of tumor-infiltrating immune cells may provide a biomarker to identify patients who might do well without trastuzumab, but we must conduct additional large clinical trials before we can consider changing clinical practice and omitting HER2-targeted therapy from the treatment regimens for patients who have high levels of tumor-infiltrating immune cells,” Perez said.

Previous research from the FinHER trial, which looked at 209 patients with HER2-positive breast cancer, reported that higher levels of TILs were associated with an increased benefit from trastuzumab.

In this study, Perez and colleagues sought to evaluate if TILs had a prognostic or predictive association with outcomes in 945 patients with HER2-positive breast cancer from the N9831 trial assigned to treatment with chemotherapy with (Arm A) or without trastuzumab (Arm C).

For this analysis, the researchers defined Str-TILs as the percent of tumor stroma that contained lymphocytic infiltrate and classified women with 60% or greater Str-TILs as having lymphocyte predominant breast cancer (LPBC). The researchers found that about 10% of women in both arms were classified as having LPBC.

The results showed that among women assigned chemotherapy alone those with LPBC had significantly better recurrence-free survival compared with those with non-LPBC (P = .004). In contrast, a woman’s level of TILs did not affect the benefit of adding trastuzumab to chemotherapy, a finding that Perez said was surprising.

When the researchers looked at the data a different way, they found that patients with LPBC assigned chemotherapy alone (Arm A) had a trend toward better outcomes compared with those assigned chemotherapy plus trastuzumab (Arm C), but the difference was not statistically significant. However, among patients with non-LPBC, women assigned to chemotherapy plus trastuzumab had significantly better recurrence-free survival than did those assigned chemotherapy alone (P < .0001).

“For the 10% of patients whose tumors were highly infiltrated with lymphocytes we cannot prove benefit to using chemotherapy plus trastuzumab,” Perez said. She added that these data are not enough to change standard of care today, but provide the impetus to conduct more research.